• WHO Solidarity Trial Consortium, Hongchao Pan, Richard Peto, Ana-Maria Henao-Restrepo, Marie-Pierre Preziosi, Vasee Sathiyamoorthy, Abdool KarimQuarraishaQThe affiliations of the members of the writing and steering committees are as follows: the Nuffield Department of Population Health and Medical Research Council Population Health Research Unit, University of Oxford, Oxford (H.P., R., Marissa M Alejandria, César Hernández García, Marie-Paule Kieny, Reza Malekzadeh, Srinivas Murthy, K Srinath Reddy, Roses PeriagoMirtaMThe affiliations of the members of the writing and steering committees are as follows: the Nuffield Department of Population Health and Medical Research Council Population Health Research Unit, University of Oxford, Oxford (H.P., R.P.),, Pierre Abi Hanna, Florence Ader, Abdullah M Al-Bader, Almonther Alhasawi, Emma Allum, Athari Alotaibi, Carlos A Alvarez-Moreno, Sheila Appadoo, Abdullah Asiri, Pål Aukrust, Andreas Barratt-Due, Samir Bellani, Mattia Branca, Heike B C Cappel-Porter, Nery Cerrato, Ting S Chow, Najada Como, Joe Eustace, Patricia J García, Sheela Godbole, Eduardo Gotuzzo, Laimonas Griskevicius, Rasha Hamra, Mariam Hassan, Mohamed Hassany, David Hutton, Irmansyah Irmansyah, Ligita Jancoriene, Jana Kirwan, Suresh Kumar, Peter Lennon, Gustavo Lopardo, Patrick Lydon, Nicola Magrini, Teresa Maguire, Suzana Manevska, Oriol Manuel, Sibylle McGinty, Marco T Medina, María L Mesa Rubio, Maria C Miranda-Montoya, Jeremy Nel, Estevao P Nunes, Markus Perola, Antonio Portolés, Menaldi R Rasmin, Aun Raza, Helen Rees, Paula P S Reges, Chris A Rogers, Kolawole Salami, Marina I Salvadori, Narvina Sinani, SterneJonathan A CJACThe affiliations of the members of the writing and steering committees are as follows: the Nuffield Department of Population Health and Medical Research Council Population Health Research Unit, University of Oxford, Oxford (H.P., R.P., Milena Stevanovikj, Evelina Tacconelli, TikkinenKari A OKAOThe affiliations of the members of the writing and steering committees are as follows: the Nuffield Department of Population Health and Medical Research Council Population Health Research Unit, University of Oxford, Oxford (H.P., R.P.),, Sven Trelle, Hala Zaid, John-Arne Røttingen, and Soumya Swaminathan.
• The affiliations of the members of the writing and steering committees are as follows: the Nuffield Department of Population Health and Medical Research Council Population Health Research Unit, University of Oxford, Oxford (H.P., R.P.), and the University of Bristol, Bristol (E.A., S.B., H.B.C.C.-P., D.H., J.K., C.A.R., J.A.C.S.) - both in the United Kingdom; the World Health Organization, Geneva (A.-M.H.-R., M.-P.P., V.S., P. Lydon, M.C.M.-M., K.S., S.S.), the University of Bern, Bern (S.A., M.B., S. McGinty, S.T.), and Lausanne University Hospital, Lausanne (O.M.) - all in Switzerland; the Centre for the AIDS Programme of Research in South Africa, Durban (Q.A.K.), and the University of the Witwatersrand (J.N.) and the Wits Reproductive Health and HIV Institute (H.R.), Johannesburg - all in South Africa; the Institute of National Epidemiology, National Institutes of Health, University of the Philippines, Manila (M.M.A.); the Agency of Medicine and Medical Devices (C.H.G.) and Hospital Clínico San Carlos, Universidad Complutense de Madrid, Spanish Clinical Research Network, Instituto de Investigación Sanitaria San Carlos (A.P.), Madrid; INSERM, Paris (M.-P.K.), and Hospices Civils de Lyon, Lyon (F.A.) - both in France; the Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran (R.M.); the University of British Columbia, Vancouver (S. Murthy), and the Public Health Agency of Canada, Ottawa (M.I.S.) - both in Canada; the Public Health Foundation of India, New Delhi (K.S.R.), and the Indian Council of Medical Research, National AIDS Research Institute, Pune (S.G.) - both in India; the National Academy of Sciences of Buenos Aires (M.R.P.) and Fundación del Centro de Estudios Infectológicos (G.L.), Buenos Aires; Rafic Hariri University Hospital (P.A.H.) and the Ministry of Public Health (R.H.), Beirut, Lebanon; the Ministry of Health (A.M.A.-B.) and Infectious Diseases Hospital (A. Alhasawi), Kuwait City, Kuwait; Universidad Nacional de Colombia and Clinica Colsanitas (C.A.A.-M.) and the Ministry of Health (M.L.M.R.), Bogota, Colombia; the Ministry for Preventive Health, Riyadh, Saudi Arabia (A. Asiri, A. Alotaibi); Oslo University Hospital (P.A., A.B.-D.) and Research Council of Norway (J.-A.R.), Oslo; Secretaria de Salud de Honduras (N. Cerrato) and the National Autonomous University of Honduras (M.T.M.), Tegucigalpa; Penang Hospital, Penang (T.S.C.), and Hospital Sungai Buloh and Jalan Hospital, Selangor (S.K.) - both in Malaysia; University Hospital Center Mother Theresa (N. Como) and the National Agency for Medicines and Medical Devices (N.S.), Tirana, Albania; the HRB Clinical Research Facility, University College Cork, Cork (J.E.), and the Department of Health and Children, Dublin (P. Lennon, T.M.) - both in Ireland; Universidad Peruana Cayetano Heredia, Lima, Peru (P.J.G., E.G.); Vilnius University Hospital Santaros Klinikos (L.G.) and Vilnius University, Institute of Clinical Medicine (L.J.), Vilnius, Lithuania; Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan (M. Hassan, A.R.); the National Hepatology and Tropical Medicine Research Institute (M. Hassany) and the Ministry of Health and Population (H.Z.), Cairo; the National Institute of Health Research and Development (I.I.) and Rumah Sakit Umum Pusat Persahabatan (M.R.R.), Jakarta, Indonesia; the Italian Medicines Agency, Rome (N.M.), and the University of Verona, Verona (E.T.) - both in Italy; the Ministry of Health (S. Manevska) and the University Clinic of Infectious Diseases and Febrile Conditions (M.S.), Skopje, North Macedonia; the Oswaldo Cruz Foundation, Rio de Janeiro (E.P.N., P.P.S.R.); and the Finnish Institute for Health and Welfare and the University of Finland (M.P.) and Helsinki University Hospital (K.A.O.T.), Helsinki, and South Karelian Central Hospital, Lappeenranta (K.A.O.T.) - all in Finland.
• N. Engl. J. Med. 2021 Feb 11; 384 (6): 497511497-511.

BackgroundWorld 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).MethodsWe 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.ResultsAt 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.ConclusionsThese 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, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).Copyright © 2020 Massachusetts Medical Society.

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