5-day versus 10-day course of remdesivir in patients with severe COVID-19

1. Compared to patients who received remdesivir for 10 days, those in the 5-day group experienced no significant difference in either clinical outcomes or time to clinical improvement.

2. Although adverse events were slightly more frequent in the 10-day group, this effect may have been related to differences in baseline clinical status rather than treatment duration.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Remdesivir is an adenosine analog prodrug whose metabolite directly inhibits RNA-dependent RNA polymerase and causes delayed chain termination. The medication has shown activity against SARS-CoV-2 in vitro as well as in primate models, and data from recent compassionate use studies and randomized controlled trials show that it may accelerate recovery from COVID-19. A 10-day course of treatment has been the standard in previous studies, but with millions of cases worldwide and the production of remdesivir proceeding at a crawl, shortening the treatment duration could reduce the length of hospital stays and increase the number of patients who can be treated with a limited drug supply. This study found that there was no significant difference in the likelihood of clinical improvement between the 5-day and 10-day groups. In fact, the 5-day group had numerically fewer deaths and a greater number of patients who had been discharged by day 14. The two groups had similar adverse event rates, but the 10-day group had over 10% more serious adverse events. This study had a high attrition rate because many patients were discharged prior to completing the full course of therapy, and the lack of a placebo arm precluded any analysis of the efficacy of remdesivir. Nonetheless, these results suggest that 10 days may not be the shortest effective duration of remdesivir therapy for COVID-19.

Click here to read the study in NEJM

Relevant Reading: Compassionate Use of Remdesivir for Patients with Severe COVID-19

In-Depth [randomized controlled trial]: In this open-label phase 3 trial, 397 patients with PCR-confirmed SARS-CoV-2 infection not requiring ventilation were randomly assigned in a 1:1 ratio to receive either a 5-day or 10-day course of intravenous remdesivir. Demographic characteristics were similar between groups, but patients in the 10-day group had significantly worse baseline clinical status compared to those in the 5-day group (P=0.02). All patients received a loading dose of 200 mg on day 1 and 100 mg per day thereafter. Efficacy was assessed using a 7-point ordinal scale with a score of 7 corresponding to discharge from the hospital and a score of 1 indicating death. At day 14, 65% of patients in the 5-day group had a clinical improvement of at least 2 points versus only 54% of those in the 10-day group. After adjusting for baseline clinical status, the distributions of final clinical status were similar between groups (P=0.14). Additionally, no significant differences were detected in recovery, time to clinical improvement, or time to recovery. 70-75% of both groups experienced at least 1 adverse event of any severity, but 35% of patients in the 10-day group had serious adverse events, as compared with 21% in the 5-day group (P<0.05). Acute kidney injury was observed in 15 patients in the 10-day group versus only 4 in the 5-day group. Some other common adverse events were nausea, constipation, and insomnia; the most common serious adverse event was respiratory failure.

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