Repurposed Antiviral Drugs for Covid-19 : Interim WHO Solidarity Trial Results
Creators: name: WHO Solidarity Trial Consortium
name: Pan, Hongchao
name: Peto, Richard
name: Henao-Restrepo, Ana-Maria
name: Preziosi, Marie-Pierre
name: Sathiyamoorthy, Vasee
name: Karim, Quarraisha Abdool
name: Alejandria, Marissa M.
name: Hernández García, César
name: Kieny, Marie-Paul
name: Malekzadeh, Reza
name: Murthy, Srinivas
name: Reddy, K. Srinath
name: Periago, Mirta Roses
name: Hanna, Pierre Abi
name: Ader, Florence
name: Al-Bader, Abdullah M.
name: Alhasawi, Almonther
name: Allum, Emma
name: Alotaibi, Athari
name: Alvarez-Moreno, Carlos A.
name: Appadoo, Sheila
name: Asiri, Abdullah
name: Aukrust, Pål
name: Barratt-Due, Andreas
name: Bellani, Samir
name: Branca, Mattia
name: Cappel-Porter, Heike B. C.
name: Cerrato, Nery
name: Chow, Ting S.
name: Como, Najada
name: Eustace, Joe
name: García, Patricia J.
name: Godbole, Sheela
name: Gotuzzo, Eduardo
name: Griskevicius, Laimonas
name: Hamra, Rasha
name: Hassan, Mariam
name: Hassany, Mohamed
name: Hutton, David
name: Irmansyah, Irmansyah
name: Jancoriene, Ligita
name: Kirwan, Jana
name: Kumar, Suresh
name: Lennon, Peter
name: Lopardo, Gustavo
name: Lydon, Patrick
name: Magrini, Nicola
name: Maguire, Teresa
name: Manevska, Suzana
name: Manuel, Oriol
name: McGinty, Sibylle
name: Medina, Marco T.
name: Mesa Rubio, María L.
name: Miranda-Montoya, Maria C.
name: Nel, Jeremy
name: Nunes, Estevao P.
name: Perola, Markus
name: Portolés, Antonio
name: Rasmin, Menaldi R.
name: Raza, Aun
name: Rees, Helen
name: Reges, Paula P. S.
name: Rogers, Chris A.
name: Salami, Kolawole
name: Salvadori, Marina I.
name: Sinani, Narvina
name: Sterne, Jonathan A. C.
name: Stevanovikj, Milena
name: Tacconelli, Evelina
name: Tikkinen, Kari A. O.
name: Trelle, Sven
name: Zaid, Hala
name: Røttingen, John-Arne
name: Swaminathan, Soumya
Publisher: name: Massachusetts Medical Society
Year: 2021

description: 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, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)