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27 results on '"Derde, L.P.G."'

1. Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

Author: Higgins, A.M., Berry, L.R., Lorenzi, E., Murthy, S., McQuilten, Z., Mouncey, P.R., Al-Beidh, F., Annane, D., Arabi, Y.M., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Charles, W.N., Cove, M., Detry, M.A., Estcourt, L.J., Fagbodun, E.O., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Horvat, C.M., Huang, D.T., Ichihara, N., Lamontagne, F., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Parry-Billings, K., Peters, S.E.C., Reyes, L.F., Rowan, K.M., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Stronach, L.M., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Gordon, A.C., Webb, S.A., Lawler, P.R., Higgins, A.M., Berry, L.R., Lorenzi, E., Murthy, S., McQuilten, Z., Mouncey, P.R., Al-Beidh, F., Annane, D., Arabi, Y.M., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Charles, W.N., Cove, M., Detry, M.A., Estcourt, L.J., Fagbodun, E.O., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Horvat, C.M., Huang, D.T., Ichihara, N., Lamontagne, F., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Parry-Billings, K., Peters, S.E.C., Reyes, L.F., Rowan, K.M., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Stronach, L.M., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Gordon, A.C., Webb, S.A., and Lawler, P.R.
Abstract: Item does not contain fulltext, IMPORTANCE: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. OBJECTIVE: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. INTERVENTIONS: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). MAIN OUTCOMES AND MEASURES: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. RESULTS: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06
Published: 2023

2. Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

Author: Higgins, A.M., Berry, L.R., Lorenzi, E., Murthy, S., McQuilten, Z., Mouncey, P.R., Al-Beidh, F., Annane, D., Arabi, Y.M., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Charles, W.N., Cove, M., Detry, M.A., Estcourt, L.J., Fagbodun, E.O., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Horvat, C.M., Huang, D.T., Ichihara, N., Lamontagne, F., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Parry-Billings, K., Peters, S.E.C., Reyes, L.F., Rowan, K.M., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Stronach, L.M., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Gordon, A.C., Pickkers, P., Webb, S.A., Lawler, P.R., Higgins, A.M., Berry, L.R., Lorenzi, E., Murthy, S., McQuilten, Z., Mouncey, P.R., Al-Beidh, F., Annane, D., Arabi, Y.M., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Charles, W.N., Cove, M., Detry, M.A., Estcourt, L.J., Fagbodun, E.O., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Horvat, C.M., Huang, D.T., Ichihara, N., Lamontagne, F., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Parry-Billings, K., Peters, S.E.C., Reyes, L.F., Rowan, K.M., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Stronach, L.M., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Gordon, A.C., Pickkers, P., Webb, S.A., and Lawler, P.R.
Abstract: Item does not contain fulltext, IMPORTANCE: The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. OBJECTIVE: To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. INTERVENTIONS: Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). MAIN OUTCOMES AND MEASURES: The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. RESULTS: Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06
Published: 2023

3. Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

Author: Lawler, P.R., Derde, L.P.G., Veerdonk, F.L. van de, McVerry, B.J., Huang, D.T., Berry, L.R., Lorenzi, E., Kimmenade, R.R.J. van, Gommans, F., Vaduganathan, M., Leaf, D.E., Baron, R.M., Kim, E.Y., Frankfurter, C., Epelman, S., Kwan, Y., Grieve, R., O'Neill, S., Sadique, Z., Puskarich, M., Marshall, J.C., Higgins, A.M., Mouncey, P.R., Rowan, K.M., Al-Beidh, F., Annane, D., Arabi, Y.M., Au, C., Beane, A., Bentum-Puijk, W. van, Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Cecconi, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Ezekowitz, J., Fitzgerald, M., Gattas, D., Godoy, L.C., Goossens, H., Haniffa, R., Harrison, D.A., Hills, T., Horvat, C.M., Ichihara, N., Lamontagne, F., Linstrum, K.M., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McQuilten, Z., Murthy, S., Nichol, A.D., Owen, D.R.J., Parke, R.L., Parker, J.C., Pollock, K.M., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Singh, V., Turgeon, A.F., Turner, A.M., Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., Berry, S., Gordon, A.C., McArthur, C.J., Webb, S.A., Lawler, P.R., Derde, L.P.G., Veerdonk, F.L. van de, McVerry, B.J., Huang, D.T., Berry, L.R., Lorenzi, E., Kimmenade, R.R.J. van, Gommans, F., Vaduganathan, M., Leaf, D.E., Baron, R.M., Kim, E.Y., Frankfurter, C., Epelman, S., Kwan, Y., Grieve, R., O'Neill, S., Sadique, Z., Puskarich, M., Marshall, J.C., Higgins, A.M., Mouncey, P.R., Rowan, K.M., Al-Beidh, F., Annane, D., Arabi, Y.M., Au, C., Beane, A., Bentum-Puijk, W. van, Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Burrell, A., Buzgau, A., Buxton, M., Cecconi, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Ezekowitz, J., Fitzgerald, M., Gattas, D., Godoy, L.C., Goossens, H., Haniffa, R., Harrison, D.A., Hills, T., Horvat, C.M., Ichihara, N., Lamontagne, F., Linstrum, K.M., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McQuilten, Z., Murthy, S., Nichol, A.D., Owen, D.R.J., Parke, R.L., Parker, J.C., Pollock, K.M., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Singh, V., Turgeon, A.F., Turner, A.M., Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., Berry, S., Gordon, A.C., McArthur, C.J., and Webb, S.A.
Abstract: Item does not contain fulltext, IMPORTANCE: Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. OBJECTIVE: To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non-critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS: Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES: The primary outcome was organ support-free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS: On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support-free days among critically ill patients was 10 (-1 to 16) in the ACE inhibitor group (n = 231), 8 (-1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support-free days compared with control were 94.9% and 95.4%, respectively. Hospital surv
Published: 2023

4. Decision-making regarding antibiotic therapy duration: An observational study of multidisciplinary meetings in the intensive care unit

Author: Janssen, R.M.E., Oerlemans, A.J.M., Hoeven, J.G. van der, Oostdijk, Evelien A. N., Derde, L.P.G., Oever, J. ten, Wertheim, H.F.L., Hulscher, M.E.J.L., Schouten, J.A., Janssen, R.M.E., Oerlemans, A.J.M., Hoeven, J.G. van der, Oostdijk, Evelien A. N., Derde, L.P.G., Oever, J. ten, Wertheim, H.F.L., Hulscher, M.E.J.L., and Schouten, J.A.
Abstract: Item does not contain fulltext
Published: 2023

5. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

Author: Bradbury C.A., Lawler P.R., Stanworth S.J., McVerry B.J., McQuilten Z., Higgins A.M., Mouncey P.R., Al-Beidh F., Rowan K.M., Berry L.R., Lorenzi E., Zarychanski R., Arabi Y.M., Annane D., Beane A., Van Bentum-Puijk W., Bhimani Z., Bihari S., Bonten M.J.M., Brunkhorst F.M., Buzgau A., Buxton M., Carrier M., Cheng A.C., Cove M., Detry M.A., Estcourt L.J., Fitzgerald M., Girard T.D., Goligher E.C., Goossens H., Haniffa R., Hills T., Huang D.T., Horvat C.M., Hunt B.J., Ichihara N., Lamontagne F., Leavis H.L., Linstrum K.M., Litton E., Marshall J.C., McAuley D.F., McGlothlin A., McGuinness S.P., Middeldorp S., Montgomery S.K., Morpeth S.C., Murthy S., Neal M.D., Nichol A.D., Parke R.L., Parker J.C., Reyes L., Saito H., Santos M.S., Saunders C.T., Serpa-Neto A., Seymour C.W., Shankar-Hari M., Singh V., Tolppa T., Turgeon A.F., Turner A.M., Van De Veerdonk F.L., Green C., Lewis R.J., Angus D.C., McArthur C.J., Berry S., Derde L.P.G., Webb S.A., Gordon A.C., Bradbury C.A., Lawler P.R., Stanworth S.J., McVerry B.J., McQuilten Z., Higgins A.M., Mouncey P.R., Al-Beidh F., Rowan K.M., Berry L.R., Lorenzi E., Zarychanski R., Arabi Y.M., Annane D., Beane A., Van Bentum-Puijk W., Bhimani Z., Bihari S., Bonten M.J.M., Brunkhorst F.M., Buzgau A., Buxton M., Carrier M., Cheng A.C., Cove M., Detry M.A., Estcourt L.J., Fitzgerald M., Girard T.D., Goligher E.C., Goossens H., Haniffa R., Hills T., Huang D.T., Horvat C.M., Hunt B.J., Ichihara N., Lamontagne F., Leavis H.L., Linstrum K.M., Litton E., Marshall J.C., McAuley D.F., McGlothlin A., McGuinness S.P., Middeldorp S., Montgomery S.K., Morpeth S.C., Murthy S., Neal M.D., Nichol A.D., Parke R.L., Parker J.C., Reyes L., Saito H., Santos M.S., Saunders C.T., Serpa-Neto A., Seymour C.W., Shankar-Hari M., Singh V., Tolppa T., Turgeon A.F., Turner A.M., Van De Veerdonk F.L., Green C., Lewis R.J., Angus D.C., McArthur C.J., Berry S., Derde L.P.G., Webb S.A., and Gordon A.C.
Abstract: Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective(s): To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participant(s): In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Intervention(s): Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from-1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Result(s): The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespe
Published: 2022

6. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

Author: Bradbury C.A., Lawler P.R., Stanworth S.J., McVerry B.J., McQuilten Z., Higgins A.M., Mouncey P.R., Al-Beidh F., Rowan K.M., Berry L.R., Lorenzi E., Zarychanski R., Arabi Y.M., Annane D., Beane A., van Bentum-Puijk W., Bhimani Z., Bihari S., Bonten M.J.M., Brunkhorst F.M., Buzgau A., Buxton M., Carrier M., Cheng A.C., Cove M., Detry M.A., Estcourt L.J., Fitzgerald M., Girard T.D., Goligher E.C., Goossens H., Haniffa R., Hills T., Huang D.T., Horvat C.M., Hunt B.J., Ichihara N., Lamontagne F., Leavis H.L., Linstrum K.M., Litton E., Marshall J.C., McAuley D.F., McGlothlin A., McGuinness S.P., Middeldorp S., Montgomery S.K., Morpeth S.C., Murthy S., Neal M.D., Nichol A.D., Parke R.L., Parker J.C., Reyes L., Saito H., Santos M.S., Saunders C.T., Serpa-Neto A., Seymour C.W., Shankar-Hari M., Singh V., Tolppa T., Turgeon A.F., Turner A.M., van de Veerdonk F.L., Green C., Lewis R.J., Angus D.C., McArthur C.J., Berry S., Derde L.P.G., Webb S.A., Gordon A.C., Bradbury C.A., Lawler P.R., Stanworth S.J., McVerry B.J., McQuilten Z., Higgins A.M., Mouncey P.R., Al-Beidh F., Rowan K.M., Berry L.R., Lorenzi E., Zarychanski R., Arabi Y.M., Annane D., Beane A., van Bentum-Puijk W., Bhimani Z., Bihari S., Bonten M.J.M., Brunkhorst F.M., Buzgau A., Buxton M., Carrier M., Cheng A.C., Cove M., Detry M.A., Estcourt L.J., Fitzgerald M., Girard T.D., Goligher E.C., Goossens H., Haniffa R., Hills T., Huang D.T., Horvat C.M., Hunt B.J., Ichihara N., Lamontagne F., Leavis H.L., Linstrum K.M., Litton E., Marshall J.C., McAuley D.F., McGlothlin A., McGuinness S.P., Middeldorp S., Montgomery S.K., Morpeth S.C., Murthy S., Neal M.D., Nichol A.D., Parke R.L., Parker J.C., Reyes L., Saito H., Santos M.S., Saunders C.T., Serpa-Neto A., Seymour C.W., Shankar-Hari M., Singh V., Tolppa T., Turgeon A.F., Turner A.M., van de Veerdonk F.L., Green C., Lewis R.J., Angus D.C., McArthur C.J., Berry S., Derde L.P.G., Webb S.A., and Gordon A.C.
Abstract: Importance: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. Objective(s): To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. Design, Setting, and Participant(s): In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). Intervention(s): Patients were randomized to receive either open-label aspirin (n=565), a P2Y12 inhibitor (n=455), or no antiplatelet therapy (control; n=529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. Result(s): The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecifie
Published: 2022

7. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Author: Bradbury, C.A., Lawler, P.R., Stanworth, S.J., McVerry, B.J., McQuilten, Z., Higgins, A.M., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Berry, L.R., Lorenzi, E., Zarychanski, R., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bihari, S., Bonten, M.J.M., Brunkhorst, F.M., Buzgau, A., Buxton, M., Carrier, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Huang, D.T., Horvat, C.M., Hunt, B.J., Ichihara, N., Lamontagne, F., Leavis, H.L., Linstrum, K.M., Litton, E., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., Middeldorp, S., Montgomery, S.K., Morpeth, S.C., Murthy, S., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Singh, V., Tolppa, T., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Pickkers, P., Schouten, J.A., Webb, S.A., Gordon, A.C., Bradbury, C.A., Lawler, P.R., Stanworth, S.J., McVerry, B.J., McQuilten, Z., Higgins, A.M., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Berry, L.R., Lorenzi, E., Zarychanski, R., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bihari, S., Bonten, M.J.M., Brunkhorst, F.M., Buzgau, A., Buxton, M., Carrier, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Huang, D.T., Horvat, C.M., Hunt, B.J., Ichihara, N., Lamontagne, F., Leavis, H.L., Linstrum, K.M., Litton, E., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., Middeldorp, S., Montgomery, S.K., Morpeth, S.C., Murthy, S., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Singh, V., Tolppa, T., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Pickkers, P., Schouten, J.A., Webb, S.A., and Gordon, A.C.
Abstract: Item does not contain fulltext, IMPORTANCE: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified c
Published: 2022

8. The Renin-Angiotensin System in Acute Lung Injury

Author: Lawler, P.R., Derde, L.P.G., McVerry, B.J., Russell, James A., Veerdonk, F.L. van de, Lawler, P.R., Derde, L.P.G., McVerry, B.J., Russell, James A., and Veerdonk, F.L. van de
Abstract: Item does not contain fulltext
Published: 2022

9. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

Author: Bradbury, C.A., Lawler, P.R., Stanworth, S.J., McVerry, B.J., McQuilten, Z., Higgins, A.M., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Berry, L.R., Lorenzi, E., Zarychanski, R., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bihari, S., Bonten, M.J.M., Brunkhorst, F.M., Buzgau, A., Buxton, M., Carrier, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Huang, D.T., Horvat, C.M., Hunt, B.J., Ichihara, N., Lamontagne, F., Leavis, H.L., Linstrum, K.M., Litton, E., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., Middeldorp, S., Montgomery, S.K., Morpeth, S.C., Murthy, S., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Singh, V., Tolppa, T., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Pickkers, P., Schouten, J.A., Webb, S.A., Gordon, A.C., Bradbury, C.A., Lawler, P.R., Stanworth, S.J., McVerry, B.J., McQuilten, Z., Higgins, A.M., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Berry, L.R., Lorenzi, E., Zarychanski, R., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Bhimani, Z., Bihari, S., Bonten, M.J.M., Brunkhorst, F.M., Buzgau, A., Buxton, M., Carrier, M., Cheng, A.C., Cove, M., Detry, M.A., Estcourt, L.J., Fitzgerald, M., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Hills, T., Huang, D.T., Horvat, C.M., Hunt, B.J., Ichihara, N., Lamontagne, F., Leavis, H.L., Linstrum, K.M., Litton, E., Marshall, J.C., McAuley, D.F., McGlothlin, A., McGuinness, S.P., Middeldorp, S., Montgomery, S.K., Morpeth, S.C., Murthy, S., Neal, M.D., Nichol, A.D., Parke, R.L., Parker, J.C., Reyes, L.F., Saito, H., Santos, M.S., Saunders, C.T., Serpa-Neto, A., Seymour, C.W., Shankar-Hari, M., Singh, V., Tolppa, T., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Derde, L.P.G., Pickkers, P., Schouten, J.A., Webb, S.A., and Gordon, A.C.
Abstract: Item does not contain fulltext, IMPORTANCE: The efficacy of antiplatelet therapy in critically ill patients with COVID-19 is uncertain. OBJECTIVE: To determine whether antiplatelet therapy improves outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: In an ongoing adaptive platform trial (REMAP-CAP) testing multiple interventions within multiple therapeutic domains, 1557 critically ill adult patients with COVID-19 were enrolled between October 30, 2020, and June 23, 2021, from 105 sites in 8 countries and followed up for 90 days (final follow-up date: July 26, 2021). INTERVENTIONS: Patients were randomized to receive either open-label aspirin (n = 565), a P2Y12 inhibitor (n = 455), or no antiplatelet therapy (control; n = 529). Interventions were continued in the hospital for a maximum of 14 days and were in addition to anticoagulation thromboprophylaxis. MAIN OUTCOMES AND MEASURES: The primary end point was organ support-free days (days alive and free of intensive care unit-based respiratory or cardiovascular organ support) within 21 days, ranging from -1 for any death in hospital (censored at 90 days) to 22 for survivors with no organ support. There were 13 secondary outcomes, including survival to discharge and major bleeding to 14 days. The primary analysis was a bayesian cumulative logistic model. An odds ratio (OR) greater than 1 represented improved survival, more organ support-free days, or both. Efficacy was defined as greater than 99% posterior probability of an OR greater than 1. Futility was defined as greater than 95% posterior probability of an OR less than 1.2 vs control. Intervention equivalence was defined as greater than 90% probability that the OR (compared with each other) was between 1/1.2 and 1.2 for 2 noncontrol interventions. RESULTS: The aspirin and P2Y12 inhibitor groups met the predefined criteria for equivalence at an adaptive analysis and were statistically pooled for further analysis. Enrollment was discontinued after the prespecified c
Published: 2022

10. The Renin-Angiotensin System in Acute Lung Injury

Author: Lawler, P.R., Derde, L.P.G., McVerry, B.J., Russell, James A., Veerdonk, F.L. van de, Lawler, P.R., Derde, L.P.G., McVerry, B.J., Russell, James A., and Veerdonk, F.L. van de
Abstract: Item does not contain fulltext
Published: 2022

11. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

Author: Gordon, A.C., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Nichol, A.D., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buzgau, A., Cheng, A.C., Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Lamontagne, F., Lawler, P.R., Leavis, H.L., Linstrum, K.M., Litton, E., Lorenzi, E., Marshall, J.C., Mayr, F.B., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Murthy, S., Orr, K., Parke, R.L., Parker, J.C., Patanwala, A.E., Pettilä, V., Rademaker, E., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Sligl, W.I., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Schouten, J.A., Pickkers, P., Webb, S.A., Derde, L.P.G., Gordon, A.C., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Nichol, A.D., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buzgau, A., Cheng, A.C., Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Lamontagne, F., Lawler, P.R., Leavis, H.L., Linstrum, K.M., Litton, E., Lorenzi, E., Marshall, J.C., Mayr, F.B., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Murthy, S., Orr, K., Parke, R.L., Parker, J.C., Patanwala, A.E., Pettilä, V., Rademaker, E., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Sligl, W.I., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Schouten, J.A., Pickkers, P., Webb, S.A., and Derde, L.P.G.
Abstract: Item does not contain fulltext, BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CO
Published: 2021

12. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Author: Goligher, E.C., Bradbury, C.A., McVerry, B.J., Lawler, P.R., Berger, J.S., Gong, M.N., Carrier, M., Reynolds, H.R., Kumar, A., Turgeon, A.F., Kornblith, L.Z., Kahn, S.R., Marshall, J.C., Kim, K.S., Houston, B.L., Derde, L.P.G., Cushman, M., Tritschler, T., Angus, D.C., Godoy, L.C., McQuilten, Z., Kirwan, B.A., Farkouh, M.E., Brooks, M.M., Lewis, R.J., Berry, L.R., Lorenzi, E., Gordon, A.C., Ahuja, T., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Contreras, A., Costantini, T.W., Brouwer, S., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Eng, H.F., Escobedo, J., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Froess, J.D., Fu, Z., Galanaud, J.P., Galen, B.T., Gandotra, S., Girard, T.D., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Haniffa, R., Hegde, S.M., Hendrickson, C.M., Higgins, A.M., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Huang, D.T., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A., King, A.J., Knudson, M.M., Kornblith, A.E., Kutcher, M.E., Laffan, M.A., Lamontagne, F., Gal, G. Le, Veerdonk, F.L. van de, Middeldorp, S., Schouten, J.A., Pickkers, P., Webb, S.A., Zarychanski, R., Goligher, E.C., Bradbury, C.A., McVerry, B.J., Lawler, P.R., Berger, J.S., Gong, M.N., Carrier, M., Reynolds, H.R., Kumar, A., Turgeon, A.F., Kornblith, L.Z., Kahn, S.R., Marshall, J.C., Kim, K.S., Houston, B.L., Derde, L.P.G., Cushman, M., Tritschler, T., Angus, D.C., Godoy, L.C., McQuilten, Z., Kirwan, B.A., Farkouh, M.E., Brooks, M.M., Lewis, R.J., Berry, L.R., Lorenzi, E., Gordon, A.C., Ahuja, T., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Contreras, A., Costantini, T.W., Brouwer, S., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Eng, H.F., Escobedo, J., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Froess, J.D., Fu, Z., Galanaud, J.P., Galen, B.T., Gandotra, S., Girard, T.D., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Haniffa, R., Hegde, S.M., Hendrickson, C.M., Higgins, A.M., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Huang, D.T., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A., King, A.J., Knudson, M.M., Kornblith, A.E., Kutcher, M.E., Laffan, M.A., Lamontagne, F., Gal, G. Le, Veerdonk, F.L. van de, Middeldorp, S., Schouten, J.A., Pickkers, P., Webb, S.A., and Zarychanski, R.
Abstract: Item does not contain fulltext, BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulati
Published: 2021

13. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Author: Lawler, P.R., Goligher, E.C., Berger, J.S., Neal, M.D., McVerry, B.J., Nicolau, J.C., Gong, M.N., Carrier, M., Rosenson, R.S., Reynolds, H.R., Turgeon, A.F., Escobedo, J., Huang, D.T., Bradbury, C.A., Houston, B.L., Kornblith, L.Z., Kumar, A., Kahn, S.R., Cushman, M., McQuilten, Z., Slutsky, A.S., Kim, K.S., Gordon, A.C., Kirwan, B.A., Brooks, M.M., Higgins, A.M., Lewis, R.J., Lorenzi, E., Berry, S.M., Berry, L.R., Aday, A.W., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Costantini, T.W., Brouwer, S., Derde, L.P.G., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Galanaud, J.P., Galen, B.T., Gandotra, S., García-Madrona, S., Girard, T.D., Godoy, L.C., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Hamburg, N.M., Haniffa, R., Hanna, G., Hanna, N., Hegde, S.M., Hendrickson, C.M., Hite, R.D., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Iyer, V.N., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A.L., King, A.J., Knudson, M.M., Kornblith, A.E., Krishnan, V., Veerdonk, F.L. van de, Schouten, J.A., Pickkers, P., Hochman, J.S., Zarychanski, R., Lawler, P.R., Goligher, E.C., Berger, J.S., Neal, M.D., McVerry, B.J., Nicolau, J.C., Gong, M.N., Carrier, M., Rosenson, R.S., Reynolds, H.R., Turgeon, A.F., Escobedo, J., Huang, D.T., Bradbury, C.A., Houston, B.L., Kornblith, L.Z., Kumar, A., Kahn, S.R., Cushman, M., McQuilten, Z., Slutsky, A.S., Kim, K.S., Gordon, A.C., Kirwan, B.A., Brooks, M.M., Higgins, A.M., Lewis, R.J., Lorenzi, E., Berry, S.M., Berry, L.R., Aday, A.W., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Costantini, T.W., Brouwer, S., Derde, L.P.G., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Galanaud, J.P., Galen, B.T., Gandotra, S., García-Madrona, S., Girard, T.D., Godoy, L.C., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Hamburg, N.M., Haniffa, R., Hanna, G., Hanna, N., Hegde, S.M., Hendrickson, C.M., Hite, R.D., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Iyer, V.N., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A.L., King, A.J., Knudson, M.M., Kornblith, A.E., Krishnan, V., Veerdonk, F.L. van de, Schouten, J.A., Pickkers, P., Hochman, J.S., and Zarychanski, R.
Abstract: Item does not contain fulltext, BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagul
Published: 2021

14. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

Author: Arabi, Y.M., Gordon, A.C., Derde, L.P.G., Nichol, A.D., Murthy, S., Beidh, F.A., Annane, D., Swaidan, L.A., Beane, A., Beasley, R., Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buxton, M., Buzgau, A., Cheng, A., Jong, Menno de, Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Fowler, R., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Huang, D.T., King, A.J., Lamontagne, F., Lawler, P.R., Lewis, R., Linstrum, K., Litton, E., Lorenzi, E., Malakouti, S., McAuley, D.F., McGlothlin, A., McGuinness, S., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Mouncey, P.R., Orr, K., Parke, R., Parker, J.C., Patanwala, A.E., Rowan, K.M., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Tong, S.Y.C., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Berry, S., Marshall, J.C., McArthur, C., Schouten, J.A., Angus, D.C., Webb, S.A., Arabi, Y.M., Gordon, A.C., Derde, L.P.G., Nichol, A.D., Murthy, S., Beidh, F.A., Annane, D., Swaidan, L.A., Beane, A., Beasley, R., Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buxton, M., Buzgau, A., Cheng, A., Jong, Menno de, Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Fowler, R., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Huang, D.T., King, A.J., Lamontagne, F., Lawler, P.R., Lewis, R., Linstrum, K., Litton, E., Lorenzi, E., Malakouti, S., McAuley, D.F., McGlothlin, A., McGuinness, S., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Mouncey, P.R., Orr, K., Parke, R., Parker, J.C., Patanwala, A.E., Rowan, K.M., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Tong, S.Y.C., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Berry, S., Marshall, J.C., McArthur, C., Schouten, J.A., Angus, D.C., and Webb, S.A.
Abstract: Item does not contain fulltext, PURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.
Published: 2021

15. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

Author: Gordon, A.C., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Nichol, A.D., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buzgau, A., Cheng, A.C., Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Lamontagne, F., Lawler, P.R., Leavis, H.L., Linstrum, K.M., Litton, E., Lorenzi, E., Marshall, J.C., Mayr, F.B., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Murthy, S., Orr, K., Parke, R.L., Parker, J.C., Patanwala, A.E., Pettilä, V., Rademaker, E., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Sligl, W.I., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Schouten, J.A., Pickkers, P., Webb, S.A., Derde, L.P.G., Gordon, A.C., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Nichol, A.D., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buzgau, A., Cheng, A.C., Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Lamontagne, F., Lawler, P.R., Leavis, H.L., Linstrum, K.M., Litton, E., Lorenzi, E., Marshall, J.C., Mayr, F.B., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Murthy, S., Orr, K., Parke, R.L., Parker, J.C., Patanwala, A.E., Pettilä, V., Rademaker, E., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Sligl, W.I., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Schouten, J.A., Pickkers, P., Webb, S.A., and Derde, L.P.G.
Abstract: Item does not contain fulltext, BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CO
Published: 2021

16. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

Author: Gordon, A.C., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Nichol, A.D., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buzgau, A., Cheng, A.C., Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Lamontagne, F., Lawler, P.R., Leavis, H.L., Linstrum, K.M., Litton, E., Lorenzi, E., Marshall, J.C., Mayr, F.B., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Murthy, S., Orr, K., Parke, R.L., Parker, J.C., Patanwala, A.E., Pettilä, V., Rademaker, E., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Sligl, W.I., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Schouten, J.A., Pickkers, P., Webb, S.A., Derde, L.P.G., Gordon, A.C., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Nichol, A.D., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buzgau, A., Cheng, A.C., Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Lamontagne, F., Lawler, P.R., Leavis, H.L., Linstrum, K.M., Litton, E., Lorenzi, E., Marshall, J.C., Mayr, F.B., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Murthy, S., Orr, K., Parke, R.L., Parker, J.C., Patanwala, A.E., Pettilä, V., Rademaker, E., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Sligl, W.I., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Schouten, J.A., Pickkers, P., Webb, S.A., and Derde, L.P.G.
Abstract: Contains fulltext : 235021.pdf (Publisher’s version ) (Open Access), BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CO
Published: 2021

17. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

Author: Arabi, Y.M., Gordon, A.C., Derde, L.P.G., Nichol, A.D., Murthy, S., Beidh, F.A., Annane, D., Swaidan, L.A., Beane, A., Beasley, R., Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buxton, M., Buzgau, A., Cheng, A., Jong, Menno de, Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Fowler, R., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Huang, D.T., King, A.J., Lamontagne, F., Lawler, P.R., Lewis, R., Linstrum, K., Litton, E., Lorenzi, E., Malakouti, S., McAuley, D.F., McGlothlin, A., McGuinness, S., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Mouncey, P.R., Orr, K., Parke, R., Parker, J.C., Patanwala, A.E., Rowan, K.M., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Tong, S.Y.C., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Berry, S., Marshall, J.C., McArthur, C., Schouten, J.A., Angus, D.C., Webb, S.A., Arabi, Y.M., Gordon, A.C., Derde, L.P.G., Nichol, A.D., Murthy, S., Beidh, F.A., Annane, D., Swaidan, L.A., Beane, A., Beasley, R., Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buxton, M., Buzgau, A., Cheng, A., Jong, Menno de, Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Fowler, R., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Huang, D.T., King, A.J., Lamontagne, F., Lawler, P.R., Lewis, R., Linstrum, K., Litton, E., Lorenzi, E., Malakouti, S., McAuley, D.F., McGlothlin, A., McGuinness, S., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Mouncey, P.R., Orr, K., Parke, R., Parker, J.C., Patanwala, A.E., Rowan, K.M., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Tong, S.Y.C., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Berry, S., Marshall, J.C., McArthur, C., Schouten, J.A., Angus, D.C., and Webb, S.A.
Abstract: Contains fulltext : 238035.pdf (Publisher’s version ) (Closed access), PURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.
Published: 2021

18. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Author: Lawler, P.R., Goligher, E.C., Berger, J.S., Neal, M.D., McVerry, B.J., Nicolau, J.C., Gong, M.N., Carrier, M., Rosenson, R.S., Reynolds, H.R., Turgeon, A.F., Escobedo, J., Huang, D.T., Bradbury, C.A., Houston, B.L., Kornblith, L.Z., Kumar, A., Kahn, S.R., Cushman, M., McQuilten, Z., Slutsky, A.S., Kim, K.S., Gordon, A.C., Kirwan, B.A., Brooks, M.M., Higgins, A.M., Lewis, R.J., Lorenzi, E., Berry, S.M., Berry, L.R., Aday, A.W., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Costantini, T.W., Brouwer, S., Derde, L.P.G., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Galanaud, J.P., Galen, B.T., Gandotra, S., García-Madrona, S., Girard, T.D., Godoy, L.C., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Hamburg, N.M., Haniffa, R., Hanna, G., Hanna, N., Hegde, S.M., Hendrickson, C.M., Hite, R.D., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Iyer, V.N., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A.L., King, A.J., Knudson, M.M., Kornblith, A.E., Krishnan, V., Veerdonk, F.L. van de, Schouten, J.A., Pickkers, P., Hochman, J.S., Zarychanski, R., Lawler, P.R., Goligher, E.C., Berger, J.S., Neal, M.D., McVerry, B.J., Nicolau, J.C., Gong, M.N., Carrier, M., Rosenson, R.S., Reynolds, H.R., Turgeon, A.F., Escobedo, J., Huang, D.T., Bradbury, C.A., Houston, B.L., Kornblith, L.Z., Kumar, A., Kahn, S.R., Cushman, M., McQuilten, Z., Slutsky, A.S., Kim, K.S., Gordon, A.C., Kirwan, B.A., Brooks, M.M., Higgins, A.M., Lewis, R.J., Lorenzi, E., Berry, S.M., Berry, L.R., Aday, A.W., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Costantini, T.W., Brouwer, S., Derde, L.P.G., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Galanaud, J.P., Galen, B.T., Gandotra, S., García-Madrona, S., Girard, T.D., Godoy, L.C., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Hamburg, N.M., Haniffa, R., Hanna, G., Hanna, N., Hegde, S.M., Hendrickson, C.M., Hite, R.D., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Iyer, V.N., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A.L., King, A.J., Knudson, M.M., Kornblith, A.E., Krishnan, V., Veerdonk, F.L. van de, Schouten, J.A., Pickkers, P., Hochman, J.S., and Zarychanski, R.
Abstract: Contains fulltext : 238101.pdf (Publisher’s version ) (Open Access), BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagul
Published: 2021

19. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Author: Goligher, E.C., Bradbury, C.A., McVerry, B.J., Lawler, P.R., Berger, J.S., Gong, M.N., Carrier, M., Reynolds, H.R., Kumar, A., Turgeon, A.F., Kornblith, L.Z., Kahn, S.R., Marshall, J.C., Kim, K.S., Houston, B.L., Derde, L.P.G., Cushman, M., Tritschler, T., Angus, D.C., Godoy, L.C., McQuilten, Z., Kirwan, B.A., Farkouh, M.E., Brooks, M.M., Lewis, R.J., Berry, L.R., Lorenzi, E., Gordon, A.C., Ahuja, T., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Contreras, A., Costantini, T.W., Brouwer, S., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Eng, H.F., Escobedo, J., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Froess, J.D., Fu, Z., Galanaud, J.P., Galen, B.T., Gandotra, S., Girard, T.D., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Haniffa, R., Hegde, S.M., Hendrickson, C.M., Higgins, A.M., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Huang, D.T., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A., King, A.J., Knudson, M.M., Kornblith, A.E., Kutcher, M.E., Laffan, M.A., Lamontagne, F., Gal, G. Le, Veerdonk, F.L. van de, Middeldorp, S., Schouten, J.A., Pickkers, P., Webb, S.A., Zarychanski, R., Goligher, E.C., Bradbury, C.A., McVerry, B.J., Lawler, P.R., Berger, J.S., Gong, M.N., Carrier, M., Reynolds, H.R., Kumar, A., Turgeon, A.F., Kornblith, L.Z., Kahn, S.R., Marshall, J.C., Kim, K.S., Houston, B.L., Derde, L.P.G., Cushman, M., Tritschler, T., Angus, D.C., Godoy, L.C., McQuilten, Z., Kirwan, B.A., Farkouh, M.E., Brooks, M.M., Lewis, R.J., Berry, L.R., Lorenzi, E., Gordon, A.C., Ahuja, T., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Contreras, A., Costantini, T.W., Brouwer, S., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Eng, H.F., Escobedo, J., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Froess, J.D., Fu, Z., Galanaud, J.P., Galen, B.T., Gandotra, S., Girard, T.D., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Haniffa, R., Hegde, S.M., Hendrickson, C.M., Higgins, A.M., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Huang, D.T., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A., King, A.J., Knudson, M.M., Kornblith, A.E., Kutcher, M.E., Laffan, M.A., Lamontagne, F., Gal, G. Le, Veerdonk, F.L. van de, Middeldorp, S., Schouten, J.A., Pickkers, P., Webb, S.A., and Zarychanski, R.
Abstract: Contains fulltext : 238100.pdf (Publisher’s version ) (Open Access), BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulati
Published: 2021

20. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

Author: Arabi, Y.M., Gordon, A.C., Derde, L.P.G., Nichol, A.D., Murthy, S., Beidh, F.A., Annane, D., Swaidan, L.A., Beane, A., Beasley, R., Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buxton, M., Buzgau, A., Cheng, A., Jong, Menno de, Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Fowler, R., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Huang, D.T., King, A.J., Lamontagne, F., Lawler, P.R., Lewis, R., Linstrum, K., Litton, E., Lorenzi, E., Malakouti, S., McAuley, D.F., McGlothlin, A., McGuinness, S., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Mouncey, P.R., Orr, K., Parke, R., Parker, J.C., Patanwala, A.E., Rowan, K.M., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Tong, S.Y.C., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Berry, S., Marshall, J.C., McArthur, C., Schouten, J.A., Angus, D.C., Webb, S.A., Arabi, Y.M., Gordon, A.C., Derde, L.P.G., Nichol, A.D., Murthy, S., Beidh, F.A., Annane, D., Swaidan, L.A., Beane, A., Beasley, R., Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buxton, M., Buzgau, A., Cheng, A., Jong, Menno de, Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Fowler, R., Girard, T.D., Goligher, E.C., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Huang, D.T., King, A.J., Lamontagne, F., Lawler, P.R., Lewis, R., Linstrum, K., Litton, E., Lorenzi, E., Malakouti, S., McAuley, D.F., McGlothlin, A., McGuinness, S., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Mouncey, P.R., Orr, K., Parke, R., Parker, J.C., Patanwala, A.E., Rowan, K.M., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Tong, S.Y.C., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Berry, S., Marshall, J.C., McArthur, C., Schouten, J.A., Angus, D.C., and Webb, S.A.
Abstract: Contains fulltext : 238035.pdf (Publisher’s version ) (Closed access), PURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.
Published: 2021

21. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

Author: Lawler, P.R., Goligher, E.C., Berger, J.S., Neal, M.D., McVerry, B.J., Nicolau, J.C., Gong, M.N., Carrier, M., Rosenson, R.S., Reynolds, H.R., Turgeon, A.F., Escobedo, J., Huang, D.T., Bradbury, C.A., Houston, B.L., Kornblith, L.Z., Kumar, A., Kahn, S.R., Cushman, M., McQuilten, Z., Slutsky, A.S., Kim, K.S., Gordon, A.C., Kirwan, B.A., Brooks, M.M., Higgins, A.M., Lewis, R.J., Lorenzi, E., Berry, S.M., Berry, L.R., Aday, A.W., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Costantini, T.W., Brouwer, S., Derde, L.P.G., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Galanaud, J.P., Galen, B.T., Gandotra, S., García-Madrona, S., Girard, T.D., Godoy, L.C., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Hamburg, N.M., Haniffa, R., Hanna, G., Hanna, N., Hegde, S.M., Hendrickson, C.M., Hite, R.D., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Iyer, V.N., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A.L., King, A.J., Knudson, M.M., Kornblith, A.E., Krishnan, V., Veerdonk, F.L. van de, Schouten, J.A., Pickkers, P., Hochman, J.S., Zarychanski, R., Lawler, P.R., Goligher, E.C., Berger, J.S., Neal, M.D., McVerry, B.J., Nicolau, J.C., Gong, M.N., Carrier, M., Rosenson, R.S., Reynolds, H.R., Turgeon, A.F., Escobedo, J., Huang, D.T., Bradbury, C.A., Houston, B.L., Kornblith, L.Z., Kumar, A., Kahn, S.R., Cushman, M., McQuilten, Z., Slutsky, A.S., Kim, K.S., Gordon, A.C., Kirwan, B.A., Brooks, M.M., Higgins, A.M., Lewis, R.J., Lorenzi, E., Berry, S.M., Berry, L.R., Aday, A.W., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Costantini, T.W., Brouwer, S., Derde, L.P.G., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Galanaud, J.P., Galen, B.T., Gandotra, S., García-Madrona, S., Girard, T.D., Godoy, L.C., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Hamburg, N.M., Haniffa, R., Hanna, G., Hanna, N., Hegde, S.M., Hendrickson, C.M., Hite, R.D., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Iyer, V.N., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A.L., King, A.J., Knudson, M.M., Kornblith, A.E., Krishnan, V., Veerdonk, F.L. van de, Schouten, J.A., Pickkers, P., Hochman, J.S., and Zarychanski, R.
Abstract: Contains fulltext : 238101.pdf (Publisher’s version ) (Open Access), BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19. METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level. RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagul
Published: 2021

22. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

Author: Goligher, E.C., Bradbury, C.A., McVerry, B.J., Lawler, P.R., Berger, J.S., Gong, M.N., Carrier, M., Reynolds, H.R., Kumar, A., Turgeon, A.F., Kornblith, L.Z., Kahn, S.R., Marshall, J.C., Kim, K.S., Houston, B.L., Derde, L.P.G., Cushman, M., Tritschler, T., Angus, D.C., Godoy, L.C., McQuilten, Z., Kirwan, B.A., Farkouh, M.E., Brooks, M.M., Lewis, R.J., Berry, L.R., Lorenzi, E., Gordon, A.C., Ahuja, T., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Contreras, A., Costantini, T.W., Brouwer, S., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Eng, H.F., Escobedo, J., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Froess, J.D., Fu, Z., Galanaud, J.P., Galen, B.T., Gandotra, S., Girard, T.D., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Haniffa, R., Hegde, S.M., Hendrickson, C.M., Higgins, A.M., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Huang, D.T., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A., King, A.J., Knudson, M.M., Kornblith, A.E., Kutcher, M.E., Laffan, M.A., Lamontagne, F., Gal, G. Le, Veerdonk, F.L. van de, Middeldorp, S., Schouten, J.A., Pickkers, P., Webb, S.A., Zarychanski, R., Goligher, E.C., Bradbury, C.A., McVerry, B.J., Lawler, P.R., Berger, J.S., Gong, M.N., Carrier, M., Reynolds, H.R., Kumar, A., Turgeon, A.F., Kornblith, L.Z., Kahn, S.R., Marshall, J.C., Kim, K.S., Houston, B.L., Derde, L.P.G., Cushman, M., Tritschler, T., Angus, D.C., Godoy, L.C., McQuilten, Z., Kirwan, B.A., Farkouh, M.E., Brooks, M.M., Lewis, R.J., Berry, L.R., Lorenzi, E., Gordon, A.C., Ahuja, T., Al-Beidh, F., Annane, D., Arabi, Y.M., Aryal, D., Kreuziger, L. Baumann, Beane, A., Bhimani, Z., Bihari, S., Billett, H.H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L.A., Chekuri, S., Chen, J.T., Cheng, A.C., Chkhikvadze, T., Coiffard, B., Contreras, A., Costantini, T.W., Brouwer, S., Detry, M.A., Duggal, A., Džavík, V., Effron, M.B., Eng, H.F., Escobedo, J., Estcourt, L.J., Everett, B.M., Fergusson, D.A., Fitzgerald, M., Fowler, R.A., Froess, J.D., Fu, Z., Galanaud, J.P., Galen, B.T., Gandotra, S., Girard, T.D., Goodman, A.L., Goossens, H., Green, C., Greenstein, Y.Y., Gross, P.L., Haniffa, R., Hegde, S.M., Hendrickson, C.M., Higgins, A.M., Hindenburg, A.A., Hope, A.A., Horowitz, J.M., Horvat, C.M., Huang, D.T., Hudock, K., Hunt, B.J., Husain, M., Hyzy, R.C., Jacobson, J.R., Jayakumar, D., Keller, N.M., Khan, A., Kim, Y., Kindzelski, A., King, A.J., Knudson, M.M., Kornblith, A.E., Kutcher, M.E., Laffan, M.A., Lamontagne, F., Gal, G. Le, Veerdonk, F.L. van de, Middeldorp, S., Schouten, J.A., Pickkers, P., Webb, S.A., and Zarychanski, R.
Abstract: Contains fulltext : 238100.pdf (Publisher’s version ) (Open Access), BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19. METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulati
Published: 2021

23. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

Author: Gordon, A.C., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Nichol, A.D., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buzgau, A., Cheng, A.C., Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Lamontagne, F., Lawler, P.R., Leavis, H.L., Linstrum, K.M., Litton, E., Lorenzi, E., Marshall, J.C., Mayr, F.B., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Murthy, S., Orr, K., Parke, R.L., Parker, J.C., Patanwala, A.E., Pettilä, V., Rademaker, E., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Sligl, W.I., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Schouten, J.A., Pickkers, P., Webb, S.A., Derde, L.P.G., Gordon, A.C., Mouncey, P.R., Al-Beidh, F., Rowan, K.M., Nichol, A.D., Arabi, Y.M., Annane, D., Beane, A., Bentum-Puijk, W. van, Berry, L.R., Bhimani, Z., Bonten, M.J.M., Bradbury, C.A., Brunkhorst, F.M., Buzgau, A., Cheng, A.C., Detry, M.A., Duffy, E.J., Estcourt, L.J., Fitzgerald, M., Goossens, H., Haniffa, R., Higgins, A.M., Hills, T.E., Horvat, C.M., Lamontagne, F., Lawler, P.R., Leavis, H.L., Linstrum, K.M., Litton, E., Lorenzi, E., Marshall, J.C., Mayr, F.B., McAuley, D.F., McGlothlin, A., McGuinness, S.P., McVerry, B.J., Montgomery, S.K., Morpeth, S.C., Murthy, S., Orr, K., Parke, R.L., Parker, J.C., Patanwala, A.E., Pettilä, V., Rademaker, E., Santos, M.S., Saunders, C.T., Seymour, C.W., Shankar-Hari, M., Sligl, W.I., Turgeon, A.F., Turner, A.M., Veerdonk, F.L. van de, Zarychanski, R., Green, C., Lewis, R.J., Angus, D.C., McArthur, C.J., Berry, S., Schouten, J.A., Pickkers, P., Webb, S.A., and Derde, L.P.G.
Abstract: Contains fulltext : 235021.pdf (Publisher’s version ) (Open Access), BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CO
Published: 2021

24. Controlling antibiotic resistance in the ICU

Author: Bonten, Marc, Derde, L.P.G., Bonten, Marc, and Derde, L.P.G.
Published: 2013

25. Controlling antibiotic resistance in the ICU

Author: Bonten, Marc, Derde, L.P.G., Bonten, Marc, and Derde, L.P.G.
Published: 2013

26. Controlling antibiotic resistance in the ICU

Author: Bonten, Marc, Derde, L.P.G., Bonten, Marc, and Derde, L.P.G.
Published: 2013

27. Controlling antibiotic resistance in the ICU

Author: Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Epidemiology & Health Economics, Intensive Care Centrum, Bonten, Marc, Derde, L.P.G., Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Epidemiology & Health Economics, Intensive Care Centrum, Bonten, Marc, and Derde, L.P.G.
Published: 2013

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27 results on '"Derde, L.P.G."'

1. Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

2. Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial.

3. Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker Initiation on Organ Support-Free Days in Patients Hospitalized With COVID-19: A Randomized Clinical Trial.

4. Decision-making regarding antibiotic therapy duration: An observational study of multidisciplinary meetings in the intensive care unit

5. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

6. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

7. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

8. The Renin-Angiotensin System in Acute Lung Injury

9. Effect of Antiplatelet Therapy on Survival and Organ Support-Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial

10. The Renin-Angiotensin System in Acute Lung Injury

11. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

12. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

13. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

14. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

15. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

16. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

17. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

18. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

19. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

20. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial

21. Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19

22. Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19

23. Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19

24. Controlling antibiotic resistance in the ICU

25. Controlling antibiotic resistance in the ICU

26. Controlling antibiotic resistance in the ICU

27. Controlling antibiotic resistance in the ICU

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