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In March 2020, the WHO initiated the SOLIDARITY trial to evaluate the effects on patients hospitalized with COVID-19 of four antiviral drugs previously used for other conditions: remdesivir, hydroxychloroquine, lopinavir, and beta interferon. In this open-label trial, 11,330 patients in 30 countries were randomized to receive standard of care (no trial drug) or one of the four antivirals depending on local availability.
At entry, 8.0% of participants were receiving mechanical ventilation. Among all patients, 28-day mortality was 11.8%. None of the four medications affected risk for death or initiation of ventilation. Comparing remdesivir with standard of care, rate ratios for in-hospital death were as follows:
Overall: 0.95 (95% confidence interval [CI], 0.81–1.11)
No mechanical ventilation at entry: 0.86 (99% CI, 0.67–1.11)
Mechanical ventilation at entry: 1.20 (99% CI, 0.80–1.80)
Pan H et al. Repurposed antiviral drugs for Covid-19 — Interim WHO solidarity trial results. N Engl J Med 2020 Dec 2; [e-pub]. (https://doi.org/10.1056/NEJMoa2023184)
Comment
The SOLIDARITY findings are sobering, as none of the repurposed antiviral medications reduced mortality. The remdesivir results in particular have triggered intense discussion because SOLIDARITY seems to send a different message than ACTT-1, a somewhat smaller randomized trial that — unlike SOLIDARITY — was placebo controlled (NEJM JW Infect Dis Dec 2020 and N Engl J Med 2020 Oct 8; [e-pub]). In both trials, remdesivir did not reduce mortality. In ACTT-1, remdesivir shortened time to recovery (10 days [remdesivir] vs. 15 days [placebo]). SOLIDARITY, with its open-label design, is less well-suited for assessing time to recovery, as both clinicians and patients knew which agent was being received. As U.S. hospitals fill up with patients with COVID-19, I believe remdesivir retains a role due to its effect on speeding recovery. What's clear from both SOLIDARITY and ACTT-1, however, is that we need better drugs to treat COVID-19.