Remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a do not reduce mortality, ventilation initiation, or hospitalization duration for coronavirus disease 2019 (COVID-19) patients, according to interim results of a World Health Organization (WHO) international open-label trial published in the New England Journal of Medicine. Hydroxychloroquine, lopinavir, and interferon have been dropped from the trial for futility, and other drugs will be added as the trial continues.
From March 22 to October 4, 2020, 11,266 patients from hospitals in 30 countries were randomly assigned to receive either remdesivir (n=2750), hydroxychloroquine (n=954), lopinavir (n=1411), interferon (n=2063), or no trial drug (n=4088). Eligible patients were 18 years or older, hospitalized with a diagnosis of COVID-19, had not received any trial drug, were not expected to be transferred elsewhere within 72 hours, and had no contraindication to any trial drug. The trial’s primary objective was to assess effects on in-hospital mortality, regardless of whether death occurred before or after day 28. The secondary outcomes were the initiation of mechanical ventilation and hospitalization duration. Treatment and follow-up were discontinued at discharge.
Most patients (81%) were younger than 70 years of age, 62% were men, 25% had diabetes, and 8% were already ventilated. Deaths occurred at a median of day 8 (interquartile range [IQR], 4-14) and patients were discharged by day 8 (IQR, 5-12).
There was an overall null effect on mortality across the four trial dugs (P >.10). The rate ratio for death was 0.95 for remdesivir (95% CI, 0.81-1.11; P =.50), 1.19 for hydroxychloroquine (95% CI, 0.89-1.59; P =.23), 1.00 for lopinavir (95% CI, 0.79-1.25; P =.97), and 1.16 for interferon (95% CI, 0.96-1.39; P =.11). Trial drugs also had no effect on patient mortality by subgroups for age, ventilation status at entry, comorbidities, geographic region, or glucocorticoid use. For secondary outcomes, no trial drug reduced the rate of ventilation initiation or time to discharge.
Earlier trials of these drugs were optimistic about their efficacy for reducing COVID-19 mortality rates, but the trials were smaller or non-randomized. Based on this WHO trial, investigators concluded that “the main need is for better treatments,” such as immune modulators or monoclonal antibodies.
Pan H, Peto R, Henao-Restrepo AM, et. Al; WHO Solidarity Trial Consortium. Repurposed antiviral drugs for Covid-19 – interim WHO solidarity trial results. N Engl J Med. Published online December 2, 2020. doi:10.1056/NEJMoa2023184