Randomized Controlled Trial
Study population and setting
584 patients at 105 hospitals in the United States, Europe, and Asia, hospitalized with moderate COVID-19 (defined as pulmonary infiltrates and room-air oxygen saturation >94%). Patients were randomized open-label 5 day course of Remdesivir, a 10 day course, or standard of care. The median age was 57 years (IQR 46-66) and 227 participants (39%) were women. 56% had cardiovascular disease, 42% had hypertension, and 40% had diabetes. Patients were enrolled if they had a positive SARS-CoV-2 PCR test within 4 days of randomization. The median duration of symptoms before day 1 in the standard care group was 9 days (IQR, 6-11 days) compared with 8 days (IQR, 5-11 days) for both groups receiving remdesivir. The primary endpoint was Day 11 clinical status based on a 7-point ordinal scale; category 1 was death, category 7 was discharged.
Summary of Main Findings
533 (91%) of the participants completed the study through day 28. 76% of the patients 5 day remdesivir group completed the assigned treatment duration, as opposed to 38% of the 10 day group. The median length of treatment was 5 days for patients in the 5-day remdesivir group and 6 days for patients in the 10-day remdesivir group (mostly due to discharge prior to completing 10 days of therapy). On day 11, patients in the 5-day remdesivir group had statistically significantly higher odds of a better clinical status distribution than those receiving standard care (odds ratio, 1.65; P = .02). The clinical status distribution on day 11 between the 10-day Remdesivir and standard care groups was not significantly different (p= .18 by Wilcoxon rank sum test). There were a total of 7 deaths across the 3 groups and no difference in all-cause mortality by group at any of the assessed time points.
Randomized controlled trial with a geographically diverse population.
The study utilized open-label design, which could have led to selection bias. No virologic data was collected, and a significant number of patients did not complete their assigned treatment duration, primarily due to hospital discharge; this occurred more frequently in the 10 day group, and could have affected the results. A related limitation is that the 10 day group actually received a median of 6 days of remdesivir; thus this is not an effective comparison of 5 versus 10 days of treatment. The median duration of symptoms prior to randomization was over a week in all groups. This could have affected the study results, as earlier administration of Remdesivir may be more efficacious than later administration. Lastly, other therapies used for SARS-CoV-2 as part of local standard of care were initially allowed. A major limitation was that the participants had moderate disease with low risk of mortality or clinical progression. It is unclear whether differences in outcomes would be observed by duration of remdesivir treatment with a sicker population.
This is the first randomized controlled trial of the use of Remdesivir in patients with moderate COVID-19.
This review was posted on: 24 September 2020