Trial of Early Antiviral Therapies During Non-Hospitalized Outpatient Window (TREAT NOW) for COVID-19 to Reduce the Burden of Illness for U.S. Service Members

Effective and widely available therapies are still needed for outpatients with COVID-19 to reduce progression to severe disease, improve symptom resolution, and expedite return to duty. We aimed to evaluate the efficacy and safety of the antiviral agent lopinavir/ritonavir for early treatment of non-hospitalized individuals diagnosed with COVID-19. The Trial of Early Antiviral Therapies during Non-hospitalized Outpatient Window (TREAT NOW) was an adaptive platform trial to evaluate potential antiviral therapies for the treatment of COVID-19. This randomized, placebo-controlled, double-blind decentralized clinical trial was coordinated by five sites within the United States. Participants were non-hospitalized adults with confirmed SARS-CoV-2 infection and six or fewer days of acute respiratory infection symptoms who were randomized to either twice daily oral lopinavir/ritonavir (400 mg/100 mg) or placebo for 14 days. Daily surveys on study days one through 16 and again on study day 28 evaluating symptoms, daily activities, and hospitalization/rehospitalization status during trial enrollment. The primary outcome was longitudinal change in an ordinal scale based on combination of symptoms, activity, and hospitalization status through Day 15 and was analyzed by use of a Bayesian longitudinal proportional odds logistic regression model for estimating the probability of a superior recovery for lopinavir/ritonavir over placebo (odds ratio [OR]>1). The primary outcome was analyzed in the intention-to-treat population and safety analyzed in the safety population of participants who received at least one dose of the allocated treatment.