11 results on '"Alexandra, Binnie"'
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2. Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial
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Karim, Ali, Tanweer, Azher, Mahin, Baqi, Alexandra, Binnie, Sergio, Borgia, François M, Carrier, Yiorgos Alexandroa, Cavayas, Nicolas, Chagnon, Matthew P, Cheng, John, Conly, Cecilia, Costiniuk, Peter, Daley, Nick, Daneman, Josh, Douglas, Catarina, Downey, Erick, Duan, Emmanuelle, Duceppe, Madeleine, Durand, Shane, English, George, Farjou, Evradiki, Fera, Patricia, Fontela, Rob, Fowler, Michael, Fralick, Anna, Geagea, Jennifer, Grant, Luke B, Harrison, Thomas, Havey, Holly, Hoang, Lauren E, Kelly, Yoav, Keynan, Kosar, Khwaja, Gail, Klein, Marina, Klein, Christophe, Kolan, Nadine, Kronfli, Francois, Lamontagne, Rob, Lau, Todd C, Lee, Nelson, Lee, Rachel, Lim, Sarah, Longo, Alexandra, Lostun, Erika, MacIntyre, Isabelle, Malhamé, Kathryn, Mangof, Marlee, McGuinty, Sonya, Mergler, Matthew P, Munan, Srinivas, Murthy, Conar, O'Neil, Daniel, Ovakim, Jesse, Papenburg, Ken, Parhar, Seema Nair, Parvathy, Chandni, Patel, Santiago, Perez-Patrigeon, Ruxandra, Pinto, Subitha, Rajakumaran, Asgar, Rishu, Malaika, Roba-Oshin, Moira, Rushton, Mariam, Saleem, Marina, Salvadori, Kim, Scherr, Kevin, Schwartz, Makeda, Semret, Michael, Silverman, Ameeta, Singh, Wendy, Sligl, Stephanie, Smith, Ranjani, Somayaji, Darrell H S, Tan, Siobhan, Tobin, Meaghan, Todd, Tuong-Vi, Tran, Alain, Tremblay, Jennifer, Tsang, Alexis, Turgeon, Erik, Vakil, Jason, Weatherald, Cedric, Yansouni, and Ryan, Zarychanski
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Male ,Canada ,Alanine ,SARS-CoV-2 ,COVID-19 ,General Medicine ,Comorbidity ,Length of Stay ,Middle Aged ,Antiviral Agents ,Respiration, Artificial ,Adenosine Monophosphate ,COVID-19 Drug Treatment ,Humans ,Female ,Hospital Mortality ,Pandemics ,Aged - Abstract
The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems.We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation.Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation.
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- 2021
3. Could treatment with immunomodulatory agents targeting IL-1, IL-6, or JAK signalling improve outcomes in patients with severe influenza pneumonia? A systematic and narrative review
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Leanne M C Hays, Melissa Black, Michael P Prunty, Srinivas Murthy, Frank L van de Veerdonk, Djillali Annane, Alexandra Binnie, Aidan Burrell, Lennie P G Derde, Anthony C Gordon, Cameron Green, Antoine Guillon, Karuna Keat, Patrick R Lawler, David C Lye, Florian B Mayr, Colin J McArthur, Danny F McAuley, Bryan J McVerry, Susan C Morpeth, Jason Phua, Mathias Pletz, Luis Felipe Reyes, Manoj Saxena, Ian Seppelt, Manu Shankar-Hari, Wendy I Sligl, Anne M Turner, Timothy M Uyeki, Gloria Vazquez-Grande, Steve A Webb, Kate Ainscough, Andrea P Haren, Thomas Hills, and Alistair Nichol
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General Medicine - Abstract
Background: Influenza is a global cause of morbidity and mortality and a significant risk for a future pandemic infection. Host hyperinflammation, similar to that seen in COVID-19, may occur in response to influenza virus pneumonia, with Janus kinase (JAK) signalling and proinflammatory cytokines Interleukin (IL)-1 and IL-6 involved. Immune modulation treatment of hospitalised and critically ill COVID-19 patients, including with IL-6 and JAK inhibitors, has been found to be beneficial. Significant interest exists in the use of immunomodulatory agents targeting these pathways in the treatment of severe influenza pneumonia. Methods: We conducted a review with both systematic and narrative methods to assess whether, in patients with severe influenza pneumonia, treatment with immunomodulatory agents targeting IL-1, IL-6 or JAK signalling, in comparison to no immune modulation, is beneficial and improves clinical outcomes. Results: Our systematic search screened 5409 records and found no randomised controlled trials of IL-1, IL-6 or JAK immunomodulatory agents in patients with severe influenza pneumonia. To support this systematic search, we provide a narrative review of the biological rationale, previous use of these agents, including in hospitalised patients with COVID-19, and an overview of their safety profiles. Conclusions: Although immune modulation has proven successful in treating hospitalised and critically ill patients with COVID-19 and a biological rationale exists for testing these agents in influenza, no agents targeting IL-1, IL-6 or JAK signalling have been assessed in randomised controlled trials of patients with severe influenza pneumonia. This highlights a significant evidence gap.
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- 2022
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4. The impact of small-group virtual patient simulator training on perceptions of individual learning process and curricular integration: a multicentre cohort study of nursing and medical students
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André Mestre, Marek Muster, Ahmed Rhassane El Adib, Hugrun Ösp Egilsdottir, Kirsten Røland Byermoen, Miguel Padilha, Thania Aguilar, Nino Tabagari, Lorraine Betts, Leila Sales, Pedro Garcia, Luo Ling, Hugo Café, Alexandra Binnie, and Ana Marreiros
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Students, Medical ,Education, Medical ,Curricular integration ,Virtual Reality ,COVID-19 ,General Medicine ,Education ,Cohort Studies ,Patient Simulation ,Learning feedback ,Clinical education ,Simulation training ,Virtual Patient Simulator ,Humans ,Students, Nursing ,Clinical Competence ,Education, Nursing ,Pandemics - Abstract
Background The COVID-19 pandemic has precipitated rapid changes in medical education to protect students and patients from the risk of infection. Virtual Patient Simulators (VPS) provide a simulated clinical environment in which students can interview and examine a patient, order tests and exams, prioritize interventions, and observe response to therapy, all with minimal risk to themselves and their patients. Like high-fidelity simulators (HFS), VPS are a tool to improve curricular integration. Unlike HFS, VPS require limited infrastructure investment and can be used in low-resource settings. Few studies have examined the impact of VPS training on clinical education. This international, multicenter cohort study was designed to assess the impact of small-group VPS training on individual learning process and curricular integration from the perspective of nursing and medical students. Methods We conducted a multi-centre, international cohort study of nursing and medical students. Baseline perceptions of individual learning process and curricular integration were assessed using a 27-item pre-session questionnaire. Students subsequently participated in small-group VPS training sessions lead by a clinical tutor and then completed a 32-item post-session questionnaire, including 25 paired items. Pre- and post-session responses were compared to determine the impact of the small-group VPS experience. Results Participants included 617 nursing and medical students from 11 institutions in 8 countries. At baseline, nursing students reported greater curricular integration and more clinical and simulation experience than did medical students. After exposure to small-group VPS training, participants reported significant improvements in 5/6 items relating to individual learning process and 7/7 items relating to curricular integration. The impact of the VPS experience was similar amongst nursing and medical students. Conclusions In this multi-centre study, perceptions of individual learning process and curricular integration improved after exposure to small-group VPS training. Nursing and medical students showed similar impact. Small-group VPS training is an accessible, low-risk educational strategy that can improve student perceptions of individual learning process and curricular integration.
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- 2021
5. Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial
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Peter Dodek, Lehana Thabane, Arnold S. Kristof, Michael G. Surette, Joanna C. Dionne, Francois Lamontagne, Ryan Zarychanski, James Kutsogiannis, Lauralyn McIntyre, David Williamson, Daniel Ovakim, Diane Heels-Ansdell, François Lauzier, Daphnée Lamarche, Dave Nagpal, Deborah J. Cook, Henry T. Stelfox, Neill K. J. Adhikari, Daniel J. Niven, Robert Cirone, Frédérick D’Aragon, Sangeeta Mehta, Rodrigo Cartin-Ceba, Erick Duan, François Marquis, Charles St-Arnaud, Alberto Goffi, Paul Hosek, Eyal Golan, Osama Loubani, Kosar Khwaja, William R. Henderson, Jan O. Friedrich, Maureen O. Meade, John Granton, Jennifer L Y Tsang, Robert W. Taylor, Paul J Lysecki, John Muscedere, Yaseen M. Arabi, Endotracheal Colonization Trial (Prospect) Investigators, Tim Karachi, Richard I. Hall, M. Elizabeth Wilcox, Nicole Zytaruk, John Marshall, François Lellouche, Alexandra Binnie, Jennie Johnstone, Patrick Archambault, Martin Girard, Margaret S. Herridge, Wendy I. Sligl, Bram Rochwerg, Gordon Wood, Ian M Ball, Shane W. English, Emmanuel Charbonney, Sébastien Trop, Steve Reynolds, Brenda Reeve, Bojan Paunovic, and Pierre Aslanian
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Diarrhea ,Male ,medicine.medical_specialty ,Population ,Placebo ,law.invention ,Randomized controlled trial ,Lactobacillus rhamnosus ,law ,Internal medicine ,medicine ,Humans ,Treatment Failure ,education ,Adverse effect ,Aged ,Original Investigation ,education.field_of_study ,biology ,business.industry ,Lacticaseibacillus rhamnosus ,Probiotics ,Hazard ratio ,Ventilator-associated pneumonia ,Pneumonia, Ventilator-Associated ,General Medicine ,Bacterial Infections ,Middle Aged ,medicine.disease ,biology.organism_classification ,Intensive care unit ,Respiration, Artificial ,Anti-Bacterial Agents ,Intensive Care Units ,Female ,business - Abstract
IMPORTANCE: Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported. OBJECTIVE: To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). DESIGN, SETTING, AND PARTICIPANTS: Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). INTERVENTIONS: Enteral L rhamnosus GG (1 × 10(10) colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. MAIN OUTCOMES AND MEASURES: The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. RESULTS: Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.] with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, –2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P
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- 2021
6. Fostering community hospital research
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Karen E.A. Burns, Oleksa G. Rewa, Deborah J. Cook, Margaret S. Herridge, Paige Gehrke, Stephanie P.T. Chan, Jennifer L Y Tsang, and Alexandra Binnie
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Canada ,education.field_of_study ,business.industry ,Research ,030503 health policy & services ,Population ,MEDLINE ,Hospitals, Community ,General Medicine ,Community hospital ,03 medical and health sciences ,0302 clinical medicine ,Nursing ,Health care ,Humans ,030212 general & internal medicine ,Sociology ,0305 other medical science ,education ,business ,Analysis - Abstract
KEY POINTS The traditional setting of health research is academic centres.[1][1],[2][2] However, Canadian health care could benefit from research conducted and started in centres where most of the population receives care with substantial potential to conduct research: community hospitals.[3][3]
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- 2019
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7. CRISPR-based strategies in infectious disease diagnosis and therapy
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Alexandra Binnie, Emanuel Fernandes, Hélder Almeida-Lousada, Ramon Andrade de Mello, and Pedro Castelo-Branco
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0301 basic medicine ,Microbiology (medical) ,CRISPR gene editing ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,030106 microbiology ,Computational biology ,Review ,Biology ,Defence system ,Diagnostic system ,Communicable Diseases ,03 medical and health sciences ,0302 clinical medicine ,Infectious disease diagnosis ,Genome editing ,CRISPR ,Animals ,Humans ,Pandemic viruses ,030212 general & internal medicine ,Molecular Targeted Therapy ,Gene Editing ,Viral infections ,Bacteria ,General Medicine ,3. Good health ,Molecular Diagnostic Techniques ,Viral genomes ,Viruses ,Infectious diseases ,Narrative review ,CRISPR-Cas Systems ,Resistant bacteria - Abstract
Purpose CRISPR gene-editing technology has the potential to transform the diagnosis and treatment of infectious diseases, but most clinicians are unaware of its broad applicability. Derived from an ancient microbial defence system, these so-called “molecular scissors” enable precise gene editing with a low error rate. However, CRISPR systems can also be targeted against pathogenic DNA or RNA sequences. This potential is being combined with innovative delivery systems to develop new therapeutic approaches to infectious diseases. Methods We searched Pubmed and Google Scholar for CRISPR-based strategies in the diagnosis and treatment of infectious diseases. Reference lists were reviewed and synthesized for narrative review. Results CRISPR-based strategies represent a novel approach to many challenging infectious diseases. CRISPR technologies can be harnessed to create rapid, low-cost diagnostic systems, as well as to identify drug-resistance genes. Therapeutic strategies, such as CRISPR systems that cleave integrated viral genomes or that target resistant bacteria, are in development. CRISPR-based therapies for emerging viruses, such as SARS-CoV-2, have also been proposed. Finally, CRISPR systems can be used to reprogram human B cells to produce neutralizing antibodies. The risks of CRISPR-based therapies include off-target and on-target modifications. Strategies to control these risks are being developed and a phase 1 clinical trials of CRISPR-based therapies for cancer and monogenic diseases are already underway. Conclusions CRISPR systems have broad applicability in the field of infectious diseases and may offer solutions to many of the most challenging human infections.
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- 2021
8. Participation of more community hospitals in randomized trials of treatments for COVID-19 is needed
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Maham Khalid, George Farjou, Erick Duan, Dimitra Fleming, Alexandra Binnie, and Jennifer L Y Tsang
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medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,MEDLINE ,General Medicine ,030204 cardiovascular system & hematology ,Hospitals community ,law.invention ,Clinical trial ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,medicine ,030212 general & internal medicine ,Letters ,Intensive care medicine ,business ,health care economics and organizations ,Coronavirus Infections - Abstract
In their CMAJ commentary, Cheng and colleagues highlight the importance of evaluating potential COVID-19 therapies systematically within randomized controlled trials (RCTs).[1][1] In addition to cost, another limiting factor for clinical trials is speed of enrolment. For researchers to derive robust
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- 2020
9. Implementation of serological and molecular tools to inform COVID-19 patient management: protocol for the GENCOV prospective cohort study
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Luke A. Devine, David B. Richardson, Shelley McLeod, Bjug Borgundvaag, Tony Mazzulli, Saranya Arnoldo, Marc Clausen, Erin Bearss, Erika Frangione, Sunakshi Chowdhary, Ahmed Taher, Allison McGeer, Jennifer Taher, Yvonne Bombard, Steven Marc Friedman, Selina Casalino, Alexandra Binnie, Jordan Lerner-Ellis, Lisa J. Strug, Zeeshan Khan, Anne-Claude Gingras, Chloe Mighton, Howard Chertkow, Jared T. Simpson, Hanna Faghfoury, Seth Stern, and Trevor J. Pugh
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medicine.medical_specialty ,Genome-wide association study ,Severity of Illness Index ,immunology ,molecular diagnostics ,03 medical and health sciences ,Antigen ,Internal medicine ,Severity of illness ,medicine ,Humans ,genetics ,Prospective Studies ,Prospective cohort study ,030304 developmental biology ,0303 health sciences ,biology ,SARS-CoV-2 ,business.industry ,030305 genetics & heredity ,COVID-19 ,Genetics and Genomics ,General Medicine ,Molecular diagnostics ,3. Good health ,Clinical trial ,Observational Studies as Topic ,biology.protein ,Medicine ,Antibody ,business ,Genome-Wide Association Study ,Cohort study - Abstract
IntroductionThere is considerable variability in symptoms and severity of COVID-19 among patients infected by the SARS-CoV-2 virus. Linking host and virus genome sequence information to antibody response and biological information may identify patient or viral characteristics associated with poor and favourable outcomes. This study aims to (1) identify characteristics of the antibody response that result in maintained immune response and better outcomes, (2) determine the impact of genetic differences on infection severity and immune response, (3) determine the impact of viral lineage on antibody response and patient outcomes and (4) evaluate patient-reported outcomes of receiving host genome, antibody and viral lineage results.Methods and analysisA prospective, observational cohort study is being conducted among adult patients with COVID-19 in the Greater Toronto Area. Blood samples are collected at baseline (during infection) and 1, 6 and 12 months after diagnosis. Serial antibody titres, isotype, antigen target and viral neutralisation will be assessed. Clinical data will be collected from chart reviews and patient surveys. Host genomes and T-cell and B-cell receptors will be sequenced. Viral genomes will be sequenced to identify viral lineage. Regression models will be used to test associations between antibody response, physiological response, genetic markers and patient outcomes. Pathogenic genomic variants related to disease severity, or negative outcomes will be identified and genome wide association will be conducted. Immune repertoire diversity during infection will be correlated with severity of COVID-19 symptoms and human leucocyte antigen-type associated with SARS-CoV-2 infection. Participants can learn their genome sequencing, antibody and viral sequencing results; patient-reported outcomes of receiving this information will be assessed through surveys and qualitative interviews.Ethics and disseminationThis study was approved by Clinical Trials Ontario Streamlined Ethics Review System (CTO Project ID: 3302) and the research ethics boards at participating hospitals. Study findings will be disseminated through peer-reviewed publications, conference presentations and end-users.
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- 2021
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10. Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results
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Carlos Guijarro, Farid Zand, Mohamed solyman Kabil, Sven Trelle, Birgitte Tholin, Belén Comeche, Johan Alexander Azañero Haro, Gonzalo Sierra Torres, Quarraisha Abdool Karim, Kari Tikkinen, Jean-michel Molina, Atousa Hakamifard, George M Varghese, Oscar Josue Ponce Ponte, Mazin Barry, Pilar Vizcarra, Niccolo Riccardi, Natalia Pérez-Macias, Aynaa AlSharidi, Nelson Lee, Alexandra Binnie, Firouzé BANI-SADR, Beatriz Díaz-Pollán, Aldo Pietro Maggioni, Ilkka Kalliala, Florian Desgranges, Anders Benjamin Kildal, Katerina Nezvalova-Henriksen, Corinne Merle, Andrés Martín Alcántara, Benjamin Gaborit, Daniel Lozano Martín, Antonio Ramos-Martinez, Miguel Villegas-Chiroque, Fredy Orlando Guevara Pulido, Ana Fernández-Cruz, Cormac McCarthy, Thesla Palanee-Phillips, Annalisa Marinosci, Abdullah Assiri, Florent Wallet, Juan Pablo Balbuena, Avik Ray, Francesc Puchades, Rajarao Mesipogu, Marjatta Sinisalo, Jonathan Sterne, Antonio Portolés, Heike Cappel-Porter, Jussi Mustonen, Jeremy Nel, BRUNO MOURVILLIER, María Consuelo Miranda Montoya, Chiara Fanciulli, L Marjukka Myllärniemi, Edinson Dante Meregildo Rodriguez, Alexy Inciarte, Mohamed Hassany, François Danion, Elena Muñez Rubio, Jean-Pierre QUENOT, Esperanza Merino de Lucas, Sheela Godbole, Luis Guillermo Barreto Rocchetti, Katerina Spasovska, William Connors, Kiana Shirani, Umang Agrawal, Srinivas Murthy, Bjorn Blomberg, Vasee Moorthy, Amith Balachandran, Antonio De Pablo Esteban, Mahnaz Amini, Dag Arne Lihaug Hoff, Zeinab Siami, Guillaume Martin-Blondel, Heng Gee Lee, Thrilok Chander Bingi, Vijay Krishnan, ANA BELEN RIVAS PATERNA, Eric D'Ortenzio, Samy Zaky, Carlos Arturo Alvarez-Moreno, Alonso Soto, VIKAS MARWAH, Marco Tulio Medina, Zaira R. Palacios-Baena, Jean-Sébastien Hulot, Miguel Angel Hueda Zavaleta, Felipe García, Francisco Fanjul, Hospices Civils de Lyon (HCL), INSERM UMR-S 606, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, PRES Sorbonne Paris-Cité, and Université Paris Denis Diderot, Université Paris Diderot - Paris 7 (UPD7), Michel-Avella, Amandine, Pan, H., Peto, R., Henao-Restrepo, A. -M., Preziosi, M. -P., Sathiyamoorthy, V., Karim, Q. A., Alejandria, M. M., Garcia, C. H., Kieny, M. -P., Malekzadeh, R., Murthy, S., Srinath Reddy, K., Periago, M. R., Hanna, P. A., Ader, F., Al-Bader, A. M., Alhasawi, A., Allum, E., Alotaibi, A., Alvarez-Moreno, C. A., Appadoo, S., Asiri, A., Aukrust, P., Barratt-Due, A., Bellani, S., Branca, M., Cappel-Porter, H. B. C., Cerrato, N., Chow, T. S., Como, N., Eustace, J., Garcia, P. J., Godbole, S., Gotuzzo, E., Griskevicius, L., Hamra, R., Hassan, M., Hassany, M., Hutton, D., Irmansyah, I., Jancoriene, L., Kirwan, J., Kumar, S., Lennon, P., Lopardo, G., Lydon, P., Magrini, N., Maguire, T., Manevska, S., Manuel, O., Mcginty, S., Medina, M. T., Mesa Rubio, M. L., Miranda-Montoya, M. C., Nel, J., Nunes, E. P., Perola, M., Portoles, A., Rasmin, M. R., Raza, A., Rees, H., Reges, P. P. S., Rogers, C. A., Salami, K., Salvadori, M. I., Sinani, N., Sterne, J. A. C., Stevanovikj, M., Tacconelli, E., Tikkinen, K. A. O., Trelle, S., Zaid, H., Rottingen, J. -A., Swaminathan S., &, Luzzati, R, Di Bella, S, Doctoral Programme in Population Health, Doctoral Programme in Biomedicine, HUS Abdominal Center, Department of Surgery, Urologian yksikkö, South Carelia Social and Health care District Eksote, HUS Heart and Lung Center, Department of Medicine, Clinicum, Department of Obstetrics and Gynecology, HUS Gynecology and Obstetrics, UCL - SSS/IREC/LTAP - Louvain Centre for Toxicology and Applied Pharmacology, and UCL - (SLuc) Service de médecine interne générale
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Male ,Kaplan Meier method ,Intention to Treat Analysi ,MESH: Treatment Failure ,MESH: Hydroxychloroquine ,remdesivir ,Rate ratio ,MESH: Intention to Treat Analysis ,MESH: Length of Stay ,law.invention ,Lopinavir/*therapeutic use ,0302 clinical medicine ,middle aged ,Medicine ,Hospital Mortality ,MESH: Respiration, Artificial ,Antiviral Agents/administration & dosage/adverse effects/*therapeutic use ,comparative study ,beta1a interferon ,MESH: Middle Aged ,Alanine ,Respiration ,adult ,clinical trial ,General Medicine ,3. Good health ,Intention to Treat Analysis ,[SDV] Life Sciences [q-bio] ,aged ,health care quality ,priority journal ,drug withdrawal ,Artificial ,Interferon ,Drug Therapy, Combination ,medicine.medical_specialty ,Initiation of ventilation ,Interferon beta-1a/*therapeutic use ,World Health Organization ,Antiviral Agents ,Article ,Duration of hospital stay ,antiviral drugs ,03 medical and health sciences ,Drug Therapy ,death ,Humans ,MESH: Hospital Mortality ,human ,MESH: Kaplan-Meier Estimate ,Aged ,MESH: Humans ,treatment duration ,extracorporeal oxygenation ,Hydroxychloroquine ,Length of Stay ,major clinical study ,mortality ,Respiration, Artificial ,Adenosine Monophosphate/*analogs & derivatives/therapeutic use ,multicenter study ,Alanine/*analogs & derivatives/therapeutic use ,MESH: Interferon beta-1a ,randomized controlled trial ,MESH: Female ,antivirus agent ,[SDV]Life Sciences [q-bio] ,MESH: Hospitalization ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,Lopinavir ,Adenosine Monophosphate ,COVID-19 ,Female ,Hospitalization ,Interferon beta-1a ,Middle Aged ,Treatment Failure ,Randomized controlled trial ,Interquartile range ,law ,MESH: COVID-19 ,MESH: Adenosine Monophosphate ,030212 general & internal medicine ,antiviral drugs, Covid-19 ,MESH: Aged ,Hydroxychloroquine/*therapeutic use ,MESH: Lopinavir ,Covid19 ,artificial ventilation ,drug therapy ,ritonavir ,hospital patient ,female ,Combination ,medicine.drug ,MESH: Antiviral Agents ,combination drug therapy ,COVID-19/*drug therapy/mortality ,Randomization ,MESH: Alanine ,drug repositioning ,drug clearance ,adenosine phosphate ,coronavirus disease 2019 ,length of stay ,Internal medicine ,controlled study ,Antiviral Agent ,Intention-to-treat analysis ,business.industry ,MESH: Male ,COVID-19 Drug Treatment ,purl.org/pe-repo/ocde/ford#3.02.00 [https] ,MESH: Drug Therapy, Combination ,3121 General medicine, internal medicine and other clinical medicine ,business - Abstract
The authors report interim results of the WHO Solidarity trial of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with Covid-19. Effects on overall mortality, initiation of ventilation, and duration of hospital stay are compared. Background World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). Methods We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. Results At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P=0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P=0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P=0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P=0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. Conclusions These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ; ClinicalTrials.gov number, .)
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- 2020
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11. Effect of hydrocortisone on mortality and organ support in patients with severe COVID-19
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Angus, Derek, Derde, Lennie, Al-Beidh, Farah, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, van Bentum-Puijk, Wilma, Berry, Lindsay, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Buzgau, Adrian, Cheng, Allen, de Jong, Menno, Detry, Michelle, Estcourt, Lise, Fitzgerald, Mark, Goossens, Herman, Green, Cameron, Haniffa, Rashan, Higgins, Alisa, Horvat, Christopher, Hullegie, Sebastiaan, Kruger, Peter, Lamontagne, Francois, Lawler, Patrick, Linstrum, Kelsey, Litton, Edward, Lorenzi, Elizabeth, Marshall, John, Mcauley, Daniel, Mcglothin, Anna, Mcguinness, Shay, Mcverry, Bryan, Montgomery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Rowan, Kathryn, Sanil, Ashish, Santos, Marlene, Saunders, Christina, Seymour, Christopher, Turner, Anne, van de Veerdonk, Frank, Venkatesh, Balasubramanian, Zarychanski, Ryan, Berry, Scott, Lewis, Roger, Mcarthur, Colin, Webb, Steven, Gordon, Anthony, NIHR, Hôpital Raymond Poincaré [AP-HP], Writing Committee for the REMAP-CAP Investigators, Farah Al-Beidh, Derek Angus, Djillali Annane, Yaseen Arabi, Wilma van Bentum-Puijk, Scott Berry, Abigail Beane, Zahra Bhimani, Marc Bonten, Charlotte Bradbury, Frank Brunkhorst, Meredith Buxton, Allen Cheng, Menno De Jong, Lennie Derde, Lise Estcourt, Herman Goossens, Anthony Gordon, Cameron Green, Rashan Haniffa, Francois Lamontagne, Patrick Lawler, Edward Litton, John Marshall, Colin McArthur, Daniel McAuley, Shay McGuinness, Bryan McVerry, Stephanie Montgomery, Paul Mouncey, Srinivas Murthy, Alistair Nichol, Rachael Parke, Kathryn Rowan, Christopher Seymour, Anne Turner, Frank van de Veerdonk, Steve Webb, Ryan Zarychanski, Lewis Campbell, Andrew Forbes, David Gattas, Stephane Heritier, Lisa Higgins, Peter Kruger, Sandra Peake, Jeffrey Presneill, Ian Seppelt, Tony Trapani, Paul Young, Sean Bagshaw, Nick Daneman, Niall Ferguson, Cheryl Misak, Marlene Santos, Sebastiaan Hullegie, Mathias Pletz, Gernot Rohde, Kathy Rowan, Brian Alexander, Kim Basile, Timothy Girard, Christopher Horvat, David Huang, Kelsey Linstrum, Jennifer Vates, Richard Beasley, Robert Fowler, Steve McGloughlin, Susan Morpeth, David Paterson, Bala Venkatesh, Tim Uyeki, Kenneth Baillie, Eamon Duffy, Rob Fowler, Thomas Hills, Katrina Orr, Asad Patanwala, Steve Tong, Mihai Netea, Shilesh Bihari, Marc Carrier, Dean Fergusson, Ewan Goligher, Ghady Haidar, Beverley Hunt, Anand Kumar, Mike Laffan, Patrick Lawless, Sylvain Lother, Peter McCallum, Saskia Middeldopr, Zoe McQuilten, Matthew Neal, John Pasi, Roger Schutgens, Simon Stanworth, Alexis Turgeon, Alexandra Weissman, Neill Adhikari, Matthew Anstey, Emily Brant, Angelique de Man, Francois Lamonagne, Marie-Helene Masse, Andrew Udy, Donald Arnold, Phillipe Begin, Richard Charlewood, Michael Chasse, Mark Coyne, Jamie Cooper, James Daly, Iain Gosbell, Heli Harvala-Simmonds, Tom Hills, Sheila MacLennan, David Menon, John McDyer, Nicole Pridee, David Roberts, Manu Shankar-Hari, Helen Thomas, Alan Tinmouth, Darrell Triulzi, Tim Walsh, Erica Wood, Carolyn Calfee, Cecilia O’Kane, Murali Shyamsundar, Pratik Sinha, Taylor Thompson, Ian Young, Shailesh Bihari, Carol Hodgson, John Laffey, Danny McAuley, Neil Orford, Ary Neto, Michelle Detry, Mark Fitzgerald, Roger Lewis, Anna McGlothlin, Ashish Sanil, Christina Saunders, Lindsay Berry, Elizabeth Lorenzi, Eliza Miller, Vanessa Singh, Claire Zammit, Wilma van Bentum Puijk, Wietske Bouwman, Yara Mangindaan, Lorraine Parker, Svenja Peters, Ilse Rietveld, Kik Raymakers, Radhika Ganpat, Nicole Brillinger, Rene Markgraf, Kate Ainscough, Kathy Brickell, Aisha Anjum, Janis-Best Lane, Alvin Richards-Belle, Michelle Saull, Daisy Wiley, Julian Bion, Jason Connor, Simon Gates, Victoria Manax, Tom van der Poll, John Reynolds, Marloes van Beurden, Evelien Effelaar, Joost Schotsman, Craig Boyd, Cain Harland, Audrey Shearer, Jess Wren, Giles Clermont, William Garrard, Kyle Kalchthaler, Andrew King, Daniel Ricketts, Salim Malakoutis, Oscar Marroquin, Edvin Music, Kevin Quinn, Heidi Cate, Karen Pearson, Joanne Collins, Jane Hanson, Penny Williams, Shane Jackson, Adeeba Asghar, Sarah Dyas, Mihaela Sutu, Sheenagh Murphy, Dawn Williamson, Nhlanhla Mguni, Alison Potter, David Porter, Jayne Goodwin, Clare Rook, Susie Harrison, Hannah Williams, Hilary Campbell, Kaatje Lomme, James Williamson, Jonathan Sheffield, Willian van’t Hoff, Phobe McCracken, Meredith Young, Jasmin Board, Emma Mart, Cameron Knott, Julie Smith, Catherine Boschert, Julia Affleck, Mahesh Ramanan, Ramsy D’Souza, Kelsey Pateman, Arif Shakih, Winston Cheung, Mark Kol, Helen Wong, Asim Shah, Atul Wagh, Joanne Simpson, Graeme Duke, Peter Chan, Brittney Cartner, Stephanie Hunter, Russell Laver, Tapaswi Shrestha, Adrian Regli, Annamaria Pellicano, James McCullough, Mandy Tallott, Nikhil Kumar, Rakshit Panwar, Gail Brinkerhoff, Cassandra Koppen, Federica Cazzola, Matthew Brain, Sarah Mineall, Roy Fischer, Vishwanath Biradar, Natalie Soar, Hayden White, Kristen Estensen, Lynette Morrison, Joanne Smith, Melanie Cooper, Monash Health, Yahya Shehabi, Wisam Al-Bassam, Amanda Hulley, Christina Whitehead, Julie Lowrey, Rebecca Gresha, James Walsham, Jason Meyer, Meg Harward, Ellen Venz, Patricia Williams, Catherine Kurenda, Kirsy Smith, Margaret Smith, Rebecca Garcia, Deborah Barge, Deborah Byrne, Kathleen Byrne, Alana Driscoll, Louise Fortune, Pierre Janin, Elizabeth Yarad, Naomi Hammond, Frances Bass, Angela Ashelford, Sharon Waterson, Steve Wedd, Robert McNamara, Heidi Buhr, Jennifer Coles, Sacha Schweikert, Bradley Wibrow, Rashmi Rauniyar, Erina Myers, Ed Fysh, Ashlish Dawda, Bhaumik Mevavala, Ed Litton, Janet Ferrier, Priya Nair, Hergen Buscher, Claire Reynolds, John Santamaria, Leanne Barbazza, Jennifer Homes, Roger Smith, Lauren Murray, Jane Brailsford, Loretta Forbes, Teena Maguire, Vasanth Mariappa, Judith Smith, Scott Simpson, Matthew Maiden, Allsion Bone, Michelle Horton, Tania Salerno, Martin Sterba, Wenli Geng, Pieter Depuydt, Jan De Waele, Liesbet De Bus, Jan Fierens, Stephanie Bracke, Brenda Reeve, William Dechert, Michaël Chassé, François Martin Carrier, Dounia Boumahni, Fatna Benettaib, Ali Ghamraoui, David Bellemare, Ève Cloutier, Charles Francoeur, François Lamontagne, Frédérick D’Aragon, Elaine Carbonneau, Julie Leblond, Gloria Vazquez-Grande, Nicole Marten, Maggie Wilson, Martin Albert, Karim Serri, Alexandros Cavayas, Mathilde Duplaix, Virginie Williams, Bram Rochwerg, Tim Karachi, Simon Oczkowski, John Centofanti, Tina Millen, Erick Duan, Jennifer Tsang, Lisa Patterson, Shane English, Irene Watpool, Rebecca Porteous, Sydney Miezitis, Lauralyn McIntyre, Laurent Brochard, Karen Burns, Gyan Sandhu, Imrana Khalid, Alexandra Binnie, Elizabeth Powell, Alexandra McMillan, Tracy Luk, Noah Aref, Zdravko Andric, Sabina Cviljevic, Renata Đimoti, Marija Zapalac, Gordan Mirković, Bruno Baršić, Marko Kutleša, Viktor Kotarski, Ana Vujaklija Brajković, Jakša Babel, Helena Sever, Lidija Dragija, Ira Kušan, Suvi Vaara, Leena Pettilä, Jonna Heinonen, Anne Kuitunen, Sari Karlsson, Annukka Vahtera, Heikki Kiiski, Sanna Ristimäki, Amine Azaiz, Cyril Charron, Mathieu Godement, Guillaume Geri, Antoine Vieillard-Baron, Franck Pourcine, Mehran Monchi, David Luis, Romain Mercier, Anne Sagnier, Nathalie Verrier, Cecile Caplin, Shidasp Siami, Christelle Aparicio, Sarah Vautier, Asma Jeblaoui, Muriel Fartoukh, Laura Courtin, Vincent Labbe, Cécile Leparco, Grégoire Muller, Mai-Anh Nay, Toufik Kamel, Dalila Benzekri, Sophie Jacquier, Emmanuelle Mercier, Delphine Chartier, Charlotte Salmon, PierreFrançois Dequin, Francis Schneider, Guillaume Morel, Sylvie L’Hotellier, Julio Badie, Fernando Daniel Berdaguer, Sylvain Malfroy, Chaouki Mezher, Charlotte Bourgoin, Bruno Megarbane, Sebastian Voicu, Nicolas Deye, Isabelle Malissin, Laetitia Sutterlin, Christophe Guitton, Cédric Darreau, Mickaël Landais, Nicolas Chudeau, Alain Robert, Pierre Moine, Nicholas Heming, Virginie Maxime, Isabelle Bossard, Tiphaine Barbarin Nicholier, Gwenhael Colin, Vanessa Zinzoni, Natacham Maquigneau, André Finn, Gabriele Kreß, Uwe Hoff, Carl Friedrich Hinrichs, Jens Nee, Mathias Pletz, Stefan Hagel, Juliane Ankert, Steffi Kolanos, Frank Bloos, Sirak Petros, Bastian Pasieka, Kevin Kunz, Peter Appelt, Bianka Schütze, Stefan Kluge, Axel Nierhaus, Dominik Jarczak, Kevin Roedl, Dirk Weismann, Anna Frey, Vivantes Klinikum Neukölln, Lorenz Reill, Michael Distler, Astrid Maselli, János Bélteczki, István Magyar, Ágnes Fazekas, Sándor Kovács, Viktória Szőke, Gábor Szigligeti, János Leszkoven, Daniel Collins, Patrick Breen, Stephen Frohlich, Ruth Whelan, Bairbre McNicholas, Michael Scully, Siobhan Casey, Maeve Kernan, Peter Doran, Michael O’Dywer, Michelle Smyth, Leanne Hayes, Oscar Hoiting, Marco Peters, Els Rengers, Mirjam Evers, Anton Prinssen, Jeroen Bosch Ziekenhuis, Koen Simons, Wim Rozendaal, F Polderman, P de Jager, M Moviat, A Paling, A Salet, Emma Rademaker, Anna Linda Peters, E de Jonge, J Wigbers, E Guilder, M Butler, Keri-Anne Cowdrey, Lynette Newby, Yan Chen, Catherine Simmonds, Rachael McConnochie, Jay Ritzema Carter, Seton Henderson, Kym Van Der Heyden, Jan Mehrtens, Tony Williams, Alex Kazemi, Rima Song, Vivian Lai, Dinu Girijadevi, Robert Everitt, Robert Russell, Danielle Hacking, Ulrike Buehner, Erin Williams, Troy Browne, Kate Grimwade, Jennifer Goodson, Owen Keet, Owen Callender, Robert Martynoga, Kara Trask, Amelia Butler, Livia Schischka, Chelsea Young, Eden Lesona, Shaanti Olatunji, Yvonne Robertson, Nuno José, Teodoro Amaro dos Santos Catorze, Tiago Nuno Alfaro de Lima Pereira, Lucilia Maria Neves Pessoa, Ricardo Manuel Castro Ferreira, Joana Margarida Pereira Sousa Bastos, Simin Aysel Florescu, Delia Stanciu, Miahela Florentina Zaharia, Alma Gabriela Kosa, Daniel Codreanu, Yaseen Marabi, Eman Al Qasim, Mohamned Moneer Hagazy, Lolowa Al Swaidan, Hatim Arishi, Rosana Muñoz-Bermúdez, Judith Marin-Corral, Anna Salazar Degracia, Francisco Parrilla Gómez, Maria Isabel Mateo López, Jorge Rodriguez Fernandez, Sheila Cárcel Fernández, Rosario Carmona Flores, Rafael León López, Carmen de la Fuente Martos, Angela Allan, Petra Polgarova, Neda Farahi, Stephen McWilliam, Daniel Hawcutt, Laura Rad, Laura O’Malley, Jennifer Whitbread, Olivia Kelsall, Laura Wild, Jessica Thrush, Hannah Wood, Karen Austin, Adrian Donnelly, Martin Kelly, Sinéad O’Kane, Declan McClintock, Majella Warnock, Paul Johnston, Linda Jude Gallagher, Clare Mc Goldrick, Moyra Mc Master, Anna Strzelecka, Rajeev Jha, Michael Kalogirou, Christine Ellis, Vinodh Krishnamurthy, Vashish Deelchand, Jon Silversides, Peter McGuigan, Kathryn Ward, Aisling O’Neill, Stephanie Finn, Barbara Phillips, Dee Mullan, Laura Oritz-Ruiz de Gordoa, Matthew Thomas, Katie Sweet, Lisa Grimmer, Rebekah Johnson, Jez Pinnell, Matt Robinson, Lisa Gledhill, Tracy Wood, Matt Morgan, Jade Cole, Helen Hill, Michelle Davies, David Antcliffe, Maie Templeton, Roceld Rojo, Phoebe Coghlan, Joanna Smee, Euan Mackay, Jon Cort, Amanda Whileman, Thomas Spencer, Nick Spittle, Vidya Kasipandian, Amit Patel, Suzanne Allibone, Roman Mary Genetu, Mohamed Ramali, Alison Ghosh, Peter Bamford, Emily London, Kathryn Cawley, Maria Faulkner, Helen Jeffrey, Tim Smith, Chris Brewer, Jane Gregory, James Limb, Amanda Cowton, Julie O’Brien, Nikitas Nikitas, Colin Wells, Liana Lankester, Mark Pulletz, Patricia Williams, Jenny Birch, Sophie Wiseman, Sarah Horton, Ana Alegria, Salah Turki, Tarek Elsefi, Nikki Crisp, Louise Allen, Iain McCullagh, Philip Robinson, Carole Hays, Maite Babio-Galan, Hannah Stevenson, Divya Khare, Meredith Pinder, Selvin Selvamoni, Amitha Gopinath, Richard Pugh, Daniel Menzies, Callum Mackay, Elizabeth Allan, Gwyneth Davies, Kathryn Puxty, Claire McCue, Susanne Cathcart, Naomi Hickey, Jane Ireland, Hakeem Yusuff, Graziella Isgro, Chris Brightling, Michelle Bourne, Michelle Craner, Malcolm Watters, Rachel Prout, Louisa Davies, Suzannah Pegler, Lynsey Kyeremeh, Gill Arbane, Karen Wilson, Linda Gomm, Federica Francia, Stephen Brett, Sonia Sousa Arias, Rebecca Elin Hall, Joanna Budd, Charlotte Small, Janine Birch, Emma Collins, Jeremy Henning, Stephen Bonner, Keith Hugill, Emanuel Cirstea, Dean Wilkinson, Michal Karlikowski, Helen Sutherland, Elva Wilhelmsen, Jane Woods, Julie North, Dhinesh Sundaran, Laszlo Hollos, Susan Coburn, Joanne Walsh, Margaret Turns, Phil Hopkins, John Smith, Harriet Noble, Maria Theresa Depante, Emma Clarey, Shondipon Laha, Mark Verlander, Alexandra Williams, Abby Huckle, Andrew Hall, Jill Cooke, Caroline Gardiner-Hill, Carolyn Maloney, Hafiz Qureshi, Neil Flint, Sarah Nicholson, Sara Southin, Andrew Nicholson, Barbara Borgatta, Ian Turner-Bone, Amie Reddy, Laura Wilding, Loku Chamara Warnapura, Ronan Agno Sathianathan, David Golden, Ciaran Hart, Jo Jones, Jonathan Bannard-Smith, Joanne Henry, Katie Birchall, Fiona Pomeroy, Rachael Quayle, Arystarch Makowski, Beata Misztal, Iram Ahmed, Thyra KyereDiabour, Kevin Naiker, Richard Stewart, Esther Mwaura, Louise Mew, Lynn Wren, Felicity Willams, Richard Innes, Patricia Doble, Joanne Hutter, Charmaine Shovelton, Benjamin Plumb, Tamas Szakmany, Vincent Hamlyn, Nancy Hawkins, Sarah Lewis, Amanda Dell, Shameer Gopal, Saibal Ganguly, Andrew Smallwood, Nichola Harris, Stella Metherell, Juan Martin Lazaro, Tabitha Newman, Simon Fletcher, Jurgens Nortje, Deirdre Fottrell-Gould, Georgina Randell, Mohsin Zaman, Einas Elmahi, Andrea Jones, Kathryn Hall, Gary Mills, Kim Ryalls, Helen Bowler, Jas Sall, Richard Bourne, Zoe Borrill, Tracey Duncan, Thomas Lamb, Joanne Shaw, Claire Fox, Jeronimo Moreno Cuesta, Kugan Xavier, Dharam Purohit, Munzir Elhassan, Dhanalakshmi Bakthavatsalam, Matthew Rowland, Paula Hutton, Archana Bashyal, Neil Davidson, Clare Hird, Manish Chhablani, Gunjan Phalod, Amy Kirkby, Simon Archer, Kimberley Netherton, Henrik Reschreiter, Julie Camsooksai, Sarah Patch, Sarah Jenkins, David Pogson, Steve Rose, Zoe Daly, Lutece Brimfield, Helen Claridge, Dhruv Parekh, Colin Bergin, Michelle Bates, Joanne Dasgin, Christopher McGhee, Malcolm Sim, Sophie Kennedy Hay, Steven Henderson, Mandeep-Kaur Phull, Abbas Zaidi, Tatiana Pogreban, Lace Paulyn Rosaroso, Daniel Harvey, Benjamin Lowe, Megan Meredith, Lucy Ryan, Anil Hormis, Rachel Walker, Dawn Collier, Sarah Kimpton, Susan Oakley, Kevin Rooney, Natalie Rodden, Emma Hughes, Nicola Thomson, Deborah McGlynn, Andrew Walden, Nicola Jacques, Holly Coles, Emma Tilney, Emma Vowell, Martin Schuster-Bruce, Sally Pitts, Rebecca Miln, Laura Purandare, Luke Vamplew, Michael Spivey, Sarah Bean, Karen Burt, Lorraine Moore, Christopher Day, Charly Gibson, Elizabeth Gordon, Letizia Zitter, Samantha Keenan, Evelyn Baker, Shiney Cherian, Sean Cutler, Anna Roynon-Reed, Kate Harrington, Ajay Raithatha, Kris Bauchmuller, Norfaizan Ahmad, Irina Grecu, Dawn Trodd, Jane Martin, Caroline Wrey Brown, Ana-Marie Arias, Thomas Craven, David Hope, Jo Singleton, Sarah Clark, Nicola Rae, Ingeborg Welters, David Oliver Hamilton, Karen Williams, Victoria Waugh, David Shaw, Zudin Puthucheary, Timothy Martin, Filipa Santos, Ruzena Uddin, Alastair Somerville, Kate Colette Tatham, Shaman Jhanji, Ethel Black, Arnold Dela Rosa, Ryan Howle, Redmond Tully, Andrew Drummond, Joy Dearden, Jennifer Philbin, Sheila Munt, Alain Vuylsteke, Charles Chan, Saji Victor, Ramprasad Matsa, Minerva Gellamucho, Ben Creagh-Brown, Joe Tooley, Laura Montague, Fiona De Beaux, Laetitia Bullman, Ian Kersiake, Carrie Demetriou, Sarah Mitchard, Lidia Ramos, Katie White, Phil Donnison, Maggie Johns, Ruth Casey, Lehentha Mattocks, Sarah Salisbury, Paul Dark, Andrew Claxton, Danielle McLachlan, Kathryn Slevin, Stephanie Lee, Jonathan Hulme, Sibet Joseph, Fiona Kinney, Ho Jan Senya, Aneta Oborska, Abdul Kayani, Bernard Hadebe, Rajalakshmi Orath Prabakaran, Lesley Nichols, Matt Thomas, Ruth Worner, Beverley Faulkner, Emma Gendall, Kati Hayes, Colin Hamilton-Davies, Carmen Chan, Celina Mfuko, Hakam Abbass, Vineela Mandadapu, Susannah Leaver, Daniel Forton, Kamal Patel, Elankumaran Paramasivam, Matthew Powell, Richard Gould, Elizabeth Wilby, Clare Howcroft, Dorota Banach, Ziortza Fernández de Pinedo Artaraz, Leilani Cabreros, Ian White, Maria Croft, Nicky Holland, Rita Pereira, Ahmed Zaki, David Johnson, Matthew Jackson, Hywel Garrard, Vera Juhaz, Alistair Roy, Anthony Rostron, Lindsey Woods, Sarah Cornell, Suresh Pillai, Rachel Harford, Tabitha Rees, Helen Ivatt, Ajay Sundara Raman, Miriam Davey, Kelvin Lee, Russell Barber, Manish Chablani, Farooq Brohi, Vijay Jagannathan, Michele Clark, Sarah Purvis, Bill Wetherill, Ahilanandan Dushianthan, Rebecca Cusack, Kim de Courcy-Golder, Simon Smith, Susan Jackson, Ben Attwood, Penny Parsons, Valerie Page, Xiao Bei Zhao, Deepali Oza, Jonathan Rhodes, Tom Anderson, Sheila Morris, Charlotte Xia Le Tai, Amy Thomas, Alexandra Keen, Stephen Digby, Nicholas Cowley, Laura Wild, David Southern, Harsha Reddy, Andy Campbell, Claire Watkins, Sara Smuts, Omar Touma, Nicky Barnes, Peter Alexander, Tim Felton, Susan Ferguson, Katharine Sellers, Joanne Bradley-Potts, David Yates, Isobel Birkinshaw, Kay Kell, Nicola Marshall, Lisa Carr-Knott, Charlotte Summers, and Mégarbane, Bruno
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[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,[SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases ,General Medicine ,[SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,Writing Committee for the REMAP-CAP Investigators ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.TOX] Life Sciences [q-bio]/Toxicology ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.TOX]Life Sciences [q-bio]/Toxicology ,General & Internal Medicine ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract ,11 Medical and Health Sciences - Abstract
Importance Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures The primary end point was organ support–free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned –1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support–free days were 0 (IQR, –1 to 15), 0 (IQR, –1 to 13), and 0 (–1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support–free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.
- Published
- 2020
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