Repurposed antiviral drugs for COVID-19: interim WHO solidarity trial results

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.

Keywords

Re-purposed antiviral drugs
COVID-19
World Health Organization
WHO

Publisher

Massachusetts Medical Society

Citation

HONGCHAO, Pan et al. Repurposed antiviral drugs for COVID-19: interim WHO solidarity trial results. New England Journal of Medicine, p. 1-15, 2 Dec. 2020.

DOI

10.1056/NEJMoa2023184

ISSN

0028-4793

Notes

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

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/44967

Type

Copyright

Open access

Collections

Share

Statistics

Metadata

Author

Affilliation

Abstract