Final trial results continue to show benefit from remdesivir for COVID-19
Click Here to Manage Email Alerts
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).
References:
- 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.
Perspective
Back to Top
Peter Chin-Hong, MD
Overall, my impressions haven't changed based on [the final results of the remdesivir] study. I think the mortality data are the biggest difference in the final report vs. the preliminary paper. There is a slightly larger trend toward mortality benefit, but still not one that is statistically significant.
The report is more robust than the initial report without a real change in findings. We went from 11 days to recovery in the remdesivir group to 10 days, and then the 15 days in the placebo group stayed unchanged. With more robust cleaning up of the data and looking at it, it seems that it is ever so slightly more different in the placebo group, with a benefit favoring remdesivir. That has not changed anything in terms of its statistical significance.
The big picture is that it does not change anything day to day on the frontlines of treating patients with COVID-19. I will still continue to use remdesivir in the way we have been using it, which is trying to find the "goldilocks moment" — probably the biggest bang for the buck is in people receiving oxygen but not too much oxygen, and that has not changed based on the findings of this study.
What this report did for me was highlight the things that we don't have. We still don't have viral load in this paper, and I think a lot of people would like to see that. Clinicians would like a more robust analysis, if possible, about time to treatment from symptom onset. I think that's another question people have had. Mortality data in subgroups and in vulnerable populations would be another area that would be helpful. The million-dollar question for ongoing trials is the role of combination therapy.
Collapse
Read more about
Click Here to Manage Email Alerts