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

Abstract

AbstractOBJECTIVESDisulfiram, 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.DESIGNA randomized, double-blind, placebo-controlled trial.SETTINGConducted at four clinical sites in Brazil between December 2020 and August 2021.PARTICIPANTS140 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.INTERVENTIONParticipants 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 RESULTSThe 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.ConclusionsAlthough 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 REGISTRATIONClinicalTrials.govIdentifier:NCT04594343Key PointsBackgroundDisulfiram has been proposed to mitigate disease progression in patients with COVID-19 by targeting the inflammasomes.QuestionDoes disulfiram, a generic drug used for alcohol use disorder, reduce the time to clinical improvement or reduce the risk of severe disease in hospitalized patients with moderate COVID-19 and with comorbidities when added to the standard of care?FindingsIn this double-blind, placebo-controlled randomized clinical trial of adults hospitalized with moderate COVID-19 in Brazil, the addition of an oral disulfiram treatment to the standard of care was safe. Still, it did not decrease the time to clinical improvement.MeaningThe study findings do not support the use of disulfiram in hospitalized patients with moderate COVID-19 in addition to the standard of care.