The US National Institutes of Health (NIH) announced that preliminary results from the Adaptive COVID-19 Treatment (ACTT) trial, testing remdesivir in hospitalised adults with COVID-19 who have generally moderate-to-severe disease, indicate that the experimental antiviral was most beneficial in those who required supplemental oxygen. Early data from the trial, which have now been published in the New England Journal of Medicine, showed that patients on remdesivir had a 31% faster time to recovery than those on placebo.
“Our findings highlight the need to identify COVID-19 cases and start antiviral treatment before the pulmonary disease progresses to require mechanical ventilation,” John H. Beigel, MD, National Institutes of Health, Bethesda, Maryland, and colleagues wrote, adding that “given high mortality despite the use of remdesivir,” it is likely that the antiviral drug would be more effective in combination with other treatments.
The study began in February and enrolled 1,063 who were randomly assigned to receive standard care plus either a 10-day course of intravenous remdesivir or placebo. The primary outcome measure is time to recovery by day 29, with recovery defined as being discharged from hospital or being medically stable enough to be discharged from hospital. As previously reported, the NIH said the median time to recovery for patients treated with remdesivir was 11 days (95% confidence interval [CI], 9 to 12), which was significantly shorter than the 15 days (95% CI, 13 to 19) seen for those in the placebo group (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001).
The NIH noted that aside from the finding about a particular benefit observed in patients who need oxygen, data about benefits in other patient subgroups were “less conclusive in this preliminary analysis.”
The ACTT results also suggested a survival benefit tied to remdesivir, which had a 14-day mortality rate of 7.1%, versus 11.9% for the placebo group (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04), although the difference was not statistically significant.
Clinicians also tracked patients’ clinical status daily using an eight-point ordinal scale ranging from fully recovered to death. In addition, they compared clinical status between the study arms on day 15 and found that the “odds of improvement in the ordinal scale were higher in the remdesivir arm than in the placebo arm.”
Among patients with a baseline ordinal score of 5 (required any supplemental oxygen; 421 patients), the rate ratio for recovery was 1.47 (95% CI, 1.17 to 1.84); among patients with a baseline score of 4 ( hospitalized, not requiring supplemental oxygen but requiring ongoing medical care; 127 patients) and those with a baseline score of 6 (hospitalized, requiring noninvasive ventilation or use of high-flow oxygen devices; 197 patients), the rate ratio estimates for recovery were 1.38 (95% CI, 0.94 to 2.03) and 1.20 (95% CI, 0.79 to 1.81), respectively. For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal scores of 7; 272 patients), the rate ratio for recovery was 0.95 (95% CI, 0.64 to 1.42). A test of interaction of treatment with baseline score on the ordinal scale was not significant.
Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%).
The NIH reported earlier this month that a clinical trial (known as ACTT 2), evaluating remdesivir in combination with the anti-inflammatory drug baricitinib compared with remdesivir alone, has begun.