PURPOSE:

• Beigel et al. sought to compare the efficacy of remdesivir vs placebo for the treatment of COVID-19
• The following is the preliminary report from this multi-centered randomized controlled trial (RCT)

METHODS:

• Multi-centered double-blind randomized placebo-controlled trial (Enrollment in effect between February 21, 2020, and April 19, 2020)
  • Adaptive Covid-19 Treatment Trial (ACTT-1)
  • Multiple sites including US (45 sites), Denmark (8), UK (5), Greece (4), Germany (3), Korea (2), Mexico (2), Spain (2), Japan (1), and Singapore (1)
• Patients were randomized (1:1) into 2 groups, stratified by study site and disease severity
  • Remdesivir: IV 200-mg loading dose on day 1 | 100-mg maintenance dose daily on days 2 to 10 or until hospital discharge or death
  • Placebo: Administered using the same schedule and volume
• Standard of care supportive care provided to all patients (based on local hospital protocols) | Addidtional experimental treatment or off-label use were not allowed from day 1 through day 29 (although prior use would not exclude a patient from this trial)
• Primary outcome: Time to recovery, which meant either
  • Discharge from hospital or
  • Patient remained in hospital for infection-control purposes only, but could have otherwise been discharged

RESULTS:

• On April 27, 2020, the data was reviewed by the safety monitoring board
• This interim analysis occurred after enrollment completed (patient enrolled more rapidly than initially anticipated)
  • The data and safety monitoring board recommended that the data be opened up to the trial team members from the National Institute of Allergy and Infectious Diseases (NIAID) due to positive preliminary findings related to improved time to recovery
• The results were then made public and treating physicians could request to unblind the treatment assignment if patient status worsening (see ‘Related ObG Topic’ below)
  • Patients in placebo group could be given remdesivir

Preliminary Results

• 1059 patients were randomized
  • Remdesivir: 538
  • Placebo: 521
  • Majority of patients were enrolled in North America 79.8%
• Median recovery time was faster for patients who received remdesivir
  • Remdesivir: 11 days (95% CI, 9 to 12)
  • Placebo: 15 days (95% CI, 13 to 19)
  • Rate ratio for recovery: 1.32; 95% CI, 1.12 to 1.55; P<0.001)
• Mortality rates (by 14 days) were lower in the remdesivir group, although not statistically significant
  • Remdesivir: 7.1%
  • Placebo: 11.9%
  • Hazard ratio for death: 0.70 (95% CI, 0.47 to 1.04)
• Serious adverse events
  • Remdesivir: 21.1%
  • Placebo: 27%

CONCLUSION:

• The study is ongoing and more results will be available following 28 days of follow-up
• However, these preliminary results indicate that remdesivir (10 day course) is superior to placebo for patients with COVID-19
• Furthermore, the authors state that

These preliminary findings support the use of remdesivir for patients who are hospitalized with Covid-19 and require supplemental oxygen therapy. However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient

Learn More – Primary Sources:

Remdesivir for the Treatment of Covid-19 — Preliminary Report

Related ObG Topics:

Remdesivir Emergency Authorization: FDA Update and Summary of Preliminary NIH Study Data

Remdesivir for COVID-19: RCT Results from 10 Hospitals in China

ARDS, Critical Care and COVID-19: ‘Surviving Sepsis Campaign’ Guidelines and Key Points