Safety and Efficacy of Disulfiram in Hospitalized Patients with Moderate COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial

Abstract

OBJECTIVES: Disulfiram, a low-cost generic drug used for alcohol dependence, holds the potential to mitigate disease progression in patients with moderate COVID-19 by targeting inflammasomes. This study aimed to evaluate the clinical efficacy and safety of disulfiram when administered alongside standard of care for the treatment of hospitalized individuals with moderate COVID-19. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Conducted at four clinical sites in Brazil between December 2020 and August 2021. PARTICIPANTS: 140 participants aged 35 and older with laboratory-confirmed SARS-CoV-2 infection, hospitalized for ≤5 days with moderate symptoms of COVID-19 were enrolled, 137 were randomized. INTERVENTION: Participants were randomized in a 1:1 ratio to receive a daily dose of 500 mg of disulfiram (N=68) or placebo (N=69) for 14 days while receiving the current standard of care. Randomization was stratified by age and comorbidities (hypertension, diabetes, and BMI ≥35). MEASUREMENTS AND MAIN RESULTS The primary outcome, median time to clinical improvement [95% CI] did not significantly differ between groups (disulfiram: 3.5 [3.00, 4.00] days; placebo: 4 [3.00, 5.00] days; P=.73). Key secondary outcomes, such as mean days (SD) on supplemental oxygen [disulfiram: 4.4 (6.61) days; placebo: 3.7 (5.80) days, P=.34], median (95% CI) time to hospital discharge [disulfiram: 6.0 (5.00, 8.00) days, placebo: 5.0 (4.00, 7.00)], proportion of participants discharged by day 8 [disulfiram (68%), placebo (63%), odds ratio: 0.801], and proportion of participants who clinically worsened [disulfiram (21%), placebo (19%), P=.79], did not reveal significant differences. While the incidence of adverse events was higher in the disulfiram group, serious adverse events and 28-day mortality were comparable between the two groups. CONCLUSIONS Although disulfiram was found to be safe in hospitalized patients with moderate COVID-19, it did not shorten the time to clinical improvement. These findings do not support the use of disulfiram alongside standard of care in this patient population. TRIAL REGISTRATION ClinicalTrials.gov Identifier:NCT04594343