Final trial results continue to show benefit from remdesivir for COVID-19
Final results from a randomized clinical trial continued to show that remdesivir shortens recovery time in hospitalized patients with COVID-19, although researchers said antiviral treatment alone is probably not sufficient for all patients.
The final report from the Adaptive COVID-19 Treatment Trial (ACCT-1) was published today in The New England Journal of Medicine. Preliminary results from the trial were published in May, and even before that, the FDA had authorized emergency use of remdesivir (Gilead Sciences) based on announced study findings.
In another paper published today in the journal, researchers reported that hydroxychloroquine does not lower incidence of death from COVID-19 among hospitalized patients.
Findings from the studies reinforce recommendations from the American College of Physicians and Infectious Diseases Society of America regarding the use of remdesivir for COVID-19, and the dangers of hydroxychloroquine.
“As Dr. Fauci mentioned, remdesivir should be considered standard of care in countries where it is available,” Kay M. Tomashek, MD, MPH, a captain with the U.S. Public Health Service and medical officer at NIH, told Healio.
ACCT-1 was a double-blind, randomized, placebo-controlled trial. Tomashek and colleagues compared 1,062 hospitalized patients with COVID-19, including 541 who received remdesivir — 200 mg on day 1 and 100 mg daily for up to 9 additional days — and 521 who received a placebo.
The researchers analyzed each patient’s time to recovery, defined as discharge from the hospital or hospitalization for only infection-control purposes. Results showed that patients given remdesivir had a median recovery time of 10 days (95% CI, 9-11), whereas patients in the placebo group had an average recovery time of 15 days (95% CI, 13-18).
Tomashek noted that, even though remdesivir decreased the time to recovery, mortality remained high — 6.7% vs. 11.9% at day 15 and 11.4% vs. 15.2% at day 29 for remdesivir and placebo, respectively.
“It is clear that treatment with an antiviral drug alone is not likely to be sufficient for all patients with COVID-19,” Tomashek said.
The researchers noted that studies are underway to evaluate remdesivir in combination with modifiers of the immune response, including the ACCT-2 (baricitinib) and ACCT-3 (interferon beta-1a) trials.
“A variety of therapeutic approaches, including novel antivirals, modifiers of the immune response or other intrinsic pathways, and combination approaches, are needed to continue to improve outcomes in patients with COVID-19,” they wrote.
Tomashek said one of the study’s major challenges was a lack of information regarding the disease’s natural history early on.
“We designed this trial in January. In January, people in the U.S. were not really as aware of the disease,” Tomashek said. “We did not know the natural history of COVID-19, and in fact we're still learning a lot about the natural history of the disease.”
In the second trial, the RECOVERY Collaborative Group performed a randomized, controlled, open-label platform trial to determine the 28-day mortality benefits of hydroxychloroquine.
In the trial, 1,561 patients received hydroxychloroquine and 3,155 were given usual care. They stopped enrolling patients in the hydroxychloroquine group before the end of the analysis due to a lack of efficacy.
Results showed that death within 28 days occurred in 27% (n = 421) of patients who received hydroxychloroquine and 25% (n = 790) of patients in the usual care arm. Additionally, among patients who did not receive mechanical ventilation, the hydroxychloroquine arm experienced an increased frequency of invasive mechanical ventilation and death compared with the usual care group (30.7% vs. 26.9%; RR = 1.14; 95% CI, 1.03-1.27).
- Beigel JH, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa2007764.
- Horby P, et al. N Engl J Med. 2020;doi:10.1056/NEJMoa2022926.