Remdesivir Linked to Five-Day Reduction in COVID-19 Hospital Stay

Finalized data from the ACTT-1 trial show antiviral agent remdesivir was superior to placebo in reduced time to recovery and lesser evidenced lower respiratory tract infections among adults hospitalized with coronavirus 2019 (COVID-19).​

The findings, published under embargo by The New England Journal of Medicine Thursday, come 5 months following preliminary results first helped the Gilead Sciences therapy receive Emergency Use Authorization (EUA) in early May.

The data also come a week after remdesivir was first administered on a five-day regimen in combination with investigative monoclonal antibodies and corticosteroids to President Donald Trump, whose highly publicized case of COVID-19 resulted in his hospitalization at Walter Reed National Military Medical Center over last weekend.

Investigators, led by John H. Beigel, MD, of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH), conducted a double-blind, randomized, placebo-controlled assessment of intravenous remdesivir in adults hospitalized with COVID-19 who had evidenced lower respiratory tract infections.

At the beginning of the trial, Beigel and colleagues were aware of little to no therapies that were efficacious for COVID-19. Remdesivir was initially identified as a promising agent due to its inhibition of SARS-CoV-2 in vitro.

“To evaluate the clinical efficacy and safety of putative investigational therapeutic agents among hospitalized adults with laboratory-confirmed COVID-19, we designed an adaptive platform trial to rapidly conduct a series of phase 3, randomized, double-blind, placebo-controlled trials,” investigators wrote.

The newest results represent an update to the preliminary report after complete follow-up.

Eligible patients enrolled from February 21 to April 19 of this year were randomized 1:1 to either 200 mg loading-dose remdesivir then 100 mg daily doses for up to 9, or placebo for up to 10 days. Beigel and colleagues sought a primary outcome of time to recovery, as per either hospital discharge or hospitalization for infection control only.

Their final assessment included 1062 patients (541 on remdesivir; 521 on placebo). Mean patient age was 58.9 years (±15.0), with nearly two-thirds (64.4%) being male and more than half (53.3%) being non-Hispanic White.

Median time from COVID-19 symptom onset to randomization was 9 days; most patients (55.2%) had ≥2 coexisting conditions. Type diabetes, hypertension, and obesity were prevalent in 30.6%, 50.7%, and 45.4% of all patients, respectively.

At baseline, 41.0% of patients required supplemental oxygen. Another 26.8% were receiving invasive mechanical ventilation or ECMO.

Patients to receive remdesivir had a median recovery time of 10 days (95% CI, 9-11), versus 15 days (95% CI, 13-18) among placebo patients, indicating a rate ratio for recovery of 1.29 for remdesivir (95% CI, 1.12-1.49; P <.001).

On an eight-category ordinal scale designed to grade hospitalization status of COVID-19 patients (with greater numbers being more severe), remdesivir patients were 50% more likely to have clinically improved by day 15 than those on placebo (odds ratio [OR], 1.50; adjusted 95% CI, 1.2-1.9).

Kaplan-Meier estimates for mortality were nearly halved (6.7%) for remdesivir patients than placebo patients (11.9%) by day 15. By day 29, patients on remdesivir had a 27% reduced risk of mortality than patients on placebo (hazard ratio [HR] 0.73; 95% CI, 0.52-1.03).

Serious adverse events were observed in one-fourth (24.6%) of patients on remedesivr, and nearly one-third (31.6%) of patients on placebo.

Investigators observed their overall findings were consistent with the preliminary results reported months ago: a ten-day regimen of remdesivir remains superior to placebo in treatment of adults hospitalized with COVID-19

“Our data also suggest that treatment with remdesivir may have prevented the progression to more severe respiratory disease, as shown by the lower proportion of serious adverse events due to respiratory failure among patients in the remdesivir group, as well as a lower incidence of new oxygen use among patients who were not receiving oxygen at enrollment and lower proportion of patients needing higher levels of respiratory support during the study,” they wrote.

They also found patient recovery persisted when the antiviral was combined with a glucocorticoid use—evidencing the findings of the recent RECOVERY trial which assessed remdesivir in combination with dexamethasone.

Despite a completion of preliminary findings which were enough to warrant an early EUA and folds of further assessment, the ACTT-1 results do show monotherapy remdesivir is still associated with a high mortality from COVID-19; as such, it is not likely sufficient for all patients as a singular treatment.

“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 concluded.​