COVID-19 research briefs: flawed trial means it remains unclear how 10-day and 5-day remdesivir treatment compare

Reference

Goldman JD, Lye DCB, Hui DS, et al. Remdesivir for 5 or 10 Days in Patients with Severe Covid-19 [published online ahead of print, 2020 May 27]. N Engl J Med. 2020;10.1056/NEJMoa2015301. doi:10.1056/NEJMoa201530.

Synopsis

Research Brief #34: The results of the ACTT-1 trial suggest that remdesivir for 10 days rather than than 5 days is more effectivefor reducing the time to recovery and possibly mortality in patients with COVID-19. In this study sponsored by Gilead, 397 hospitalized patients were randomized to 5 vs 10 days of remdesivir (200 mg loading dose on day 1 followed by 100 mg daily). The study had two major flaws that limit our ability to interpret its conclusion that results were similar for the two groups. First, this was an open label trial, so patients and physicians knew who was getting the medication and for how long. Second, there were clinically important differences between groups at baseline, with more patients requiring high flow oxygen, mechanical ventilation, or ECMO in the 10-day group at baseline (69 vs 53). In the ACTT-1 trial, those patients appeared to benefit less from remdesivir. There is also no description of how randomization was performed or whether allocation to groups was concealed, so it seems likely that sicker patients were non-randomly allocated to the 10 day group. The primary outcome was improvement of at least 2 grades on a 7 point scale ranging from death (grade 1) to - not hospitalized - (grade 7); all patients started at grades 2 to 5. Improvement occurred more often in those in the 5 day group (65% vs 54%), but this difference was no longer statistically significant after adjustment for baseline differences. The final assessment of the authors is that there is no difference in outcomes between 5 and 10 days, so 5 days should be considered, especially if supplies are limited.