Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results.
Level 2 - randomized trial
Multicenter randomized controlled trial
PubMed 33264556 · doi:10.1056/NEJMoa2023184
What was done
In an open-label trial at 405 hospitals across 30 countries, 11,330 hospitalized adult patients with Covid-19 were randomly assigned to locally available trial regimens (2750 remdesivir, 954 hydroxychloroquine, 1411 lopinavir without interferon, 2063 interferon beta-1a) or open control without the trial drug (4088 patients). The intention-to-treat primary analysis examined in-hospital mortality in pairwise comparisons between each drug and its concurrent control, stratified by age and baseline mechanical ventilation status.
What was found
Across 1253 total reported deaths, Kaplan-Meier 28-day mortality was 11.8% (39.0% with baseline ventilation, 9.5% without). In-hospital death occurred in 301 of 2743 patients on remdesivir versus 303 of 2708 controls (rate ratio [RR], 0.95; 95% CI, 0.81 to 1.11; P = 0.50); 104 of 947 on hydroxychloroquine versus 84 of 906 controls (RR, 1.19; 95% CI, 0.89 to 1.59; P = 0.23); 148 of 1399 on lopinavir versus 146 of 1372 controls (RR, 1.00; 95% CI, 0.79 to 1.25; P = 0.97); and 243 of 2050 on interferon versus 216 of 2050 controls (RR, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No trial drug significantly reduced mortality overall, in any subgroup, or reduced ventilation initiation or hospitalization duration.
Why it matters
This international trial demonstrates that four widely considered repurposed antiviral regimens provide little to no clinical benefit regarding mortality, ventilation need, or hospital stay in hospitalized Covid-19 patients.
Limits
The study evaluated only hospitalized patients and cannot determine efficacy in outpatient or early illness settings. The trial was open-label without placebos, drug availability varied across participating hospitals, and treatment crossover occurred in 2 to 6% of participants.
Cited by
- supports Remdesivir demonstrated greater efficacy early in the course of COVID-19 compared to late-stage disease in patients on mechanical ventilators.