Odds of better clinical status were higher for patients with moderate COVID-19 who received a 5-day course of remdesivir than for those receiving standard care, according to the most recent randomized clinical trial of the antiviral drug.
The latest randomized clinical trial of remdesivir for treating coronavirus disease 2019 (COVID-19) examined the drug’s effect in patients with moderate disease and came up with uncertain results suggesting modest clinical benefits.
The randomized, open-label, phase 3 trial, published in JAMA Network, provides more information—and raises more questions—about the drug that has been in high demand since the US Food and Drug Administration issued Emergency Use Authorization for it in May.
“Among patients with moderate COVID-19, those randomized to a 10-day course of remdesivir did not have a statistically significant difference in clinical status compared with standard care at 11 days after initiation of treatment,” the authors wrote. “Patients randomized to a 5-day course of remdesivir had a statistically significant difference in clinical status compared with standard care, but the difference was of uncertain clinical importance.”
The trial, led by Christop D. Spinner, MD, of Technical University of Munich, School of Medicine in Germany and sponsored by Gilead Sciences, involved 584 patients at 105 hospitals in the United States, Europe, and Asia. Participants were randomized in three groups, with 197 receiving a 10-day course of remdesivir, 199 receiving a 5-day course of remdesivir, and 200 receiving standard care.
Participants were age 12 or older, and had confirmed SARS-CoV-2 infection, radiographic evidence of pulmonary infiltrates, and an ability to maintain an oxygen saturation greater than 94%.
The primary endpoint was clinical status based on a 7-point ordinal scale ranging from death to discharged.
“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; 95% CI, 1.09-2.48; P = .02),” the study authors reported. “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). By day 28, 9 patients had died: 2 (1%) in the 5-day remdesivir group, 3 (2%) in the 10-day remdesivir group, and 4 (2%) in the standard care group. Nausea (10% vs 3%), hypokalemia (6% vs 2%), and headache (5% vs 3%) were more frequent among remdesivir-treated patients compared with standard care.”
The US Food and Drug Administration expanded its Emergency Use Authorization for remdesivir for patients with moderate COVID-19 on Aug. 28. It previously was authorized for those hospitalized with the disease.
In an editorial on in JAMA Network, Erin K. McCreary, PharmD, and Derek C. Angus, M.D., MPH, of the UPMC Health System and The University of Pittsburgh School of Medicine, wrote that “there are now 3 RCTs of remdesivir in hospitalized patients with differing results, raising the question of whether the discrepancies are artifacts of study design choices, including patient populations, or whether the drug is less efficacious than hoped.”
The first randomized clinical trial, involving 237 patients with severe COVID-19 in 10 hospitals in Hubei, China, found no statistically significant clinical benefits to remdesivir.
The ACTT-1 study, involving 1063 patients, found that remdesivir was superior to placebo in shortening the time to recovery by 4 days compared with placebo in adults hospitalized with COVID-19 and evidence of lower respiratory tract infection.
Another randomized trial involving 397 patients published in May was unable to determine a significant difference in clinical improvement between a 5-day and 10-day course of remdesivir.
McCreary and Angus noted that important questions remain, including optimal patient population, optimal duration, effect on discrete clinical outcomes and the relative effect of the drug if given in the presence of dexamethasone or other corticosteroids.
“It therefore seems prudent to urgently conduct further evaluations of remdesivir in large-scale RCTs designed to address the residual uncertainties and inform optimal use,” they wrote.