Respiratory disease due to COVID-19 has taken the lives of more than 400,000 people worldwide to date and sent economies into freefall. A press release in late April suggested that remdesivir may improve clinical outcomes among patients with COVID-19. Now we have preliminary study results providing much-anticipated information about this potential therapy, a viral RNA polymerase inhibitor previously used to treat Ebola with in vitro activity against coronaviruses.
The Adaptive COVID-19 Treatment Trial-1 (ACTT-1) was a multicenter trial which randomized hospitalized adults with COVID-19 to either remdesivir 200 mg once followed by 100 mg daily for up to 10 days or placebo. Preliminary data were released prior to publication while follow-up was ongoing because the number of recovered patients exceeded the estimated number needed to demonstrate benefit. A total of 1,063 participants had been randomized when the dataset was locked for analysis. After excluding participants still receiving treatment or with missing treatment data, 1,059 participants were included in analysis (538 remdesivir vs. 521 placebo). Participants had a mean age of 59 years, more than half had at least two medical comorbidities, 20 percent identified as Black or African American, and more than 20 percent identified as Hispanic. Nearly 90 percent of participants required oxygen therapy and 25.6 percent required intubation or extracorporeal membrane oxygenation (ECMO). The primary outcome was changed from clinical status at day 15 on an eight-point ordinal scale to time to recovery in the 28 days after enrollment. This change was recommended very early in the trial, as investigators recognized that the illness lasted longer than 15 days in many patients. Recovery was defined as no longer requiring hospital care, although patients requiring isolation or home oxygen were considered recovered.
Patients randomized to the remdesevir group had a shorter median time to recovery compared to placebo (11 days vs. 15 days, rate ratio 1.32, 95% CI 1.12-1.55). Odds of improvement at day 15 were also significantly greater in the remdesivir group compared to placebo (odds ratio 1.5, 95% CI 1.18-1.91). Rates of major adverse effects and therapy discontinuation were similar between groups, as was treatment effect when adjusted for baseline ordinal score. In subgroup analysis, there was no difference in the rate of recovery among those requiring high flow oxygen, positive pressure ventilation, intubation, or ECMO at enrollment. The difference in mortality at 14 days was not statistically significant (hazard ratio for death 0.7, 95% CI 0.47-1.04), but the confidence intervals do not exclude the possibility that a difference exists and could be demonstrated if the study was repeated with a larger sample size.
Shortening disease duration by four days provides meaningful benefit for patients and healthcare systems. The authors indicate that the final dataset has similar findings to these preliminary findings. Mortality rates were similar between the two groups, however, suggesting that we must continue to search for alternative therapies and interventions. Remdesivir may not be a miracle drug, but this trial provides some of the strongest evidence to date for repurposing a therapy for immediate use.
For more information, see the topic COVID-19 (Novel Coronavirus) in DynaMed®.
EBM Focus articles provide concise summaries of clinical trials most likely to inform clinical practice curated by the DynaMed editorial team.
