1. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial
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Marconi, V, Ramanan, A, de Bono, S, Kartman, C, Krishnan, V, Liao, R, Piruzeli, M, Goldman, J, Alatorre-Alexander, J, de Cassia Pellegrini, R, Estrada, V, Som, M, Cardoso, A, Chakladar, S, Crowe, B, Reis, P, Zhang, X, Adams, D, Ely, E, Ahn, M, Akasbi, M, Altclas, J, Ariel, F, Ariza, H, Atkar, C, Bertetti, A, Bhattacharya, M, Briones, M, Budhraja, A, Burza, A, Camacho Ortiz, A, Caricchio, R, Casas, M, Cevoli Recio, V, Choi, W, Cohen, E, Comulada-Rivera, A, Cook, P, Cornejo Juarez, D, Daniel, C, Degrecci Relvas, L, Dominguez Cherit, J, Ellerin, T, Enikeev, D, Erico Tanni Minamoto, S, Fiss, E, Furuichi, M, Giovanni Luz, K, Gonzalez, O, Gordeev, I, Gruenewald, T, Hamamoto Sato, V, Heo, E, Heo, J, Hermida, M, Hirai, Y, Hutchinson, D, Iastrebner, C, Ioachimescu, O, Jain, M, Juliani Souza Lima, M, Khan, A, Kremer, A, Lawrie, T, Macelwee, M, Madhani-Lovely, F, Malhotra, V, Martinez Resendez, M, Mckinnell, J, Milligan, P, Minelli, C, Moran Rodriguez, M, Parody, M, Paulin, P, Pellegrini, R, Pemu, P, Procopio Carvalho, A, Puoti, M, Purow, J, Ramesh, M, Rea Neto, A, Robinson, P, Rodrigues, C, Rojas Velasco, G, Saraiva, J, Scheinberg, M, Schreiber, S, Scublinsky, D, Sevciovic Grumach, A, Shawa, I, Simon Campos, J, Sofat, N, Spinner, C, Sprinz, E, Stienecker, R, Suarez, J, Tachikawa, N, Tahir, H, Tiffany, B, Vishnevsky, A, Westheimer Cavalcante, A, Zirpe, K, Marconi V. C., Ramanan A. V., de Bono S., Kartman C. E., Krishnan V., Liao R., Piruzeli M. L. B., Goldman J. D., Alatorre-Alexander J., de Cassia Pellegrini R., Estrada V., Som M., Cardoso A., Chakladar S., Crowe B., Reis P., Zhang X., Adams D. H., Ely E. W., Ahn M. -Y., Akasbi M., Altclas J. D., Ariel F., Ariza H. A., Atkar C., Bertetti A., Bhattacharya M., Briones M. L., Budhraja A., Burza A., Camacho Ortiz A., Caricchio R., Casas M., Cevoli Recio V., Choi W. S., Cohen E., Comulada-Rivera A., Cook P., Cornejo Juarez D. P., Daniel C., Degrecci Relvas L. F., Dominguez Cherit J. G., Ellerin T., Enikeev D., Erico Tanni Minamoto S., Fiss E., Furuichi M., Giovanni Luz K., Gonzalez O., Gordeev I., Gruenewald T., Hamamoto Sato V. A., Heo E. Y., Heo J. Y., Hermida M., Hirai Y., Hutchinson D., Iastrebner C., Ioachimescu O., Jain M., Juliani Souza Lima M. P., Khan A., Kremer A. E., Lawrie T., MacElwee M., Madhani-Lovely F., Malhotra V., Martinez Resendez M. F., McKinnell J., Milligan P., Minelli C., Moran Rodriguez M. A., Parody M. L., Paulin P., Pellegrini R. D. C., Pemu P., Procopio Carvalho A. C., Puoti M., Purow J., Ramesh M., Rea Neto A., Robinson P., Rodrigues C., Rojas Velasco G., Saraiva J. F. K., Scheinberg M., Schreiber S., Scublinsky D., Sevciovic Grumach A., Shawa I., Simon Campos J., Sofat N., Spinner C. D., Sprinz E., Stienecker R., Suarez J., Tachikawa N., Tahir H., Tiffany B., Vishnevsky A., Westheimer Cavalcante A., Zirpe K., Marconi, V, Ramanan, A, de Bono, S, Kartman, C, Krishnan, V, Liao, R, Piruzeli, M, Goldman, J, Alatorre-Alexander, J, de Cassia Pellegrini, R, Estrada, V, Som, M, Cardoso, A, Chakladar, S, Crowe, B, Reis, P, Zhang, X, Adams, D, Ely, E, Ahn, M, Akasbi, M, Altclas, J, Ariel, F, Ariza, H, Atkar, C, Bertetti, A, Bhattacharya, M, Briones, M, Budhraja, A, Burza, A, Camacho Ortiz, A, Caricchio, R, Casas, M, Cevoli Recio, V, Choi, W, Cohen, E, Comulada-Rivera, A, Cook, P, Cornejo Juarez, D, Daniel, C, Degrecci Relvas, L, Dominguez Cherit, J, Ellerin, T, Enikeev, D, Erico Tanni Minamoto, S, Fiss, E, Furuichi, M, Giovanni Luz, K, Gonzalez, O, Gordeev, I, Gruenewald, T, Hamamoto Sato, V, Heo, E, Heo, J, Hermida, M, Hirai, Y, Hutchinson, D, Iastrebner, C, Ioachimescu, O, Jain, M, Juliani Souza Lima, M, Khan, A, Kremer, A, Lawrie, T, Macelwee, M, Madhani-Lovely, F, Malhotra, V, Martinez Resendez, M, Mckinnell, J, Milligan, P, Minelli, C, Moran Rodriguez, M, Parody, M, Paulin, P, Pellegrini, R, Pemu, P, Procopio Carvalho, A, Puoti, M, Purow, J, Ramesh, M, Rea Neto, A, Robinson, P, Rodrigues, C, Rojas Velasco, G, Saraiva, J, Scheinberg, M, Schreiber, S, Scublinsky, D, Sevciovic Grumach, A, Shawa, I, Simon Campos, J, Sofat, N, Spinner, C, Sprinz, E, Stienecker, R, Suarez, J, Tachikawa, N, Tahir, H, Tiffany, B, Vishnevsky, A, Westheimer Cavalcante, A, Zirpe, K, Marconi V. C., Ramanan A. V., de Bono S., Kartman C. E., Krishnan V., Liao R., Piruzeli M. L. B., Goldman J. D., Alatorre-Alexander J., de Cassia Pellegrini R., Estrada V., Som M., Cardoso A., Chakladar S., Crowe B., Reis P., Zhang X., Adams D. H., Ely E. W., Ahn M. -Y., Akasbi M., Altclas J. D., Ariel F., Ariza H. A., Atkar C., Bertetti A., Bhattacharya M., Briones M. L., Budhraja A., Burza A., Camacho Ortiz A., Caricchio R., Casas M., Cevoli Recio V., Choi W. S., Cohen E., Comulada-Rivera A., Cook P., Cornejo Juarez D. P., Daniel C., Degrecci Relvas L. F., Dominguez Cherit J. G., Ellerin T., Enikeev D., Erico Tanni Minamoto S., Fiss E., Furuichi M., Giovanni Luz K., Gonzalez O., Gordeev I., Gruenewald T., Hamamoto Sato V. A., Heo E. Y., Heo J. Y., Hermida M., Hirai Y., Hutchinson D., Iastrebner C., Ioachimescu O., Jain M., Juliani Souza Lima M. P., Khan A., Kremer A. E., Lawrie T., MacElwee M., Madhani-Lovely F., Malhotra V., Martinez Resendez M. F., McKinnell J., Milligan P., Minelli C., Moran Rodriguez M. A., Parody M. L., Paulin P., Pellegrini R. D. C., Pemu P., Procopio Carvalho A. C., Puoti M., Purow J., Ramesh M., Rea Neto A., Robinson P., Rodrigues C., Rojas Velasco G., Saraiva J. F. K., Scheinberg M., Schreiber S., Scublinsky D., Sevciovic Grumach A., Shawa I., Simon Campos J., Sofat N., Spinner C. D., Sprinz E., Stienecker R., Suarez J., Tachikawa N., Tahir H., Tiffany B., Vishnevsky A., Westheimer Cavalcante A., and Zirpe K.
- Abstract
Background: Baricitinib is an oral selective Janus kinase 1/2 inhibitor with known anti-inflammatory properties. This study evaluates the efficacy and safety of baricitinib in combination with standard of care for the treatment of hospitalised adults with COVID-19. Methods: In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT04421027. Findings: Between June 11, 2020, and Jan 15, 2021, 1525 participants were randomly assigned to the baricitinib group (n=764) or the placebo group (n=761). 1204 (79·3%) of 1518 participants with available data were receiving systemic corticosteroids at baseline, of whom 1099 (91·3%) were on dexamethasone; 287 (18·9%) participants were receiving remdesivir. Overall, 27·8% of participants receiving baricitinib and 30·5% receiving placebo progressed to meet the primary endpoint (odds ratio 0·85 [95% CI 0·67 to 1·08], p=0·18), with an absolute risk difference of −2·7 percentage points (
- Published
- 2021