TDF/FTC for HIGH-RISK PATIENTS with COVID-19: The PANCOVID RANDOMIZED CLINICAL TRIAL

ABSTRACT

Background: Some in vitro, animal, and epidemiological data suggest that tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) might be an efficacious treatment for COVID-19 Methods: In a multicenter open-label, pragmatic, randomized trial in 25 hospitals in Spain we included participants with symptomatic SARS-CoV-2 detected by PCR or antigenic test, with a creatinine clearance > 60 mL/min, > 60 years or younger if they had at least 2 comorbidities (hypertension, obesity, diabetes, cirrhosis, chronic neurologic disease, active cancer, heart failure, coronary heart disease or COPD). Participants were randomized to receive or not TDF/FTC. Randomization was stratified by age group, symptoms duration (< or ≥ 5 days) and health care setting (hospitalized, long-term care facility, ambulatory). Primary outcome was 28 days mortality. Secondary outcomes were disease progression (increased O2 requirements, need for mechanical ventilation or increase in medical therapy steroid dose, need for tocilizumab). At any moment during the trial participants with room air O2 saturation < 95% and ≥ 1 increased inflammatory biomarker could be randomized to dexamethasone (D) or dexamethasone plus baricitinib (DB) Results: 355 participants included (TDF/FTC n=177, no TDF/FTC n=178), median age 67 years (IQR 62-73), male (64.5%), median days of symptoms 8 (IQR 5-10), 29% with < 5 days of symptoms, 96.9% hospitalized, 35.5% with 1 and 36.6 % with ≥ 2 comorbidities (62.8% hypertension, 9.3% diabetes, 1.7% obesity), median room air SaO2 95% (IQR 94-96), 63% receiving O2 and 11.8% Remdesivir. 74% of participants were simultaneously randomized to D or DB. There were not statistically significant differences in endpoints in participants not treated vs.treated with TDF/FTC mortality 2.2%/4.0%, disease progression 23.6%/22.0%, deferred randomization to D or DB 6.7%/6.2%, mechanical ventilation (invasive or noninvasive) 22.5%/20.3%, days since randomization until discharge (median [IQR]) 7 [5,14]/6 [4,12], discharge before 28 days 91.9%/89.7%. By Cox regression Hazard Ratio (95% CI) of 28-day mortality was 1.96 (0.55-7.01) for participants treated with TDF/FTC. Serious adverse events occurred in 6.18%/5.65% of participants not treated/treated with TDF/FTC. Adverse events leading to TDF/FTC discontinuation occurred in 2.26%. Conclusion: In this clinical trial of high-risk patients with COVID-19 TDF/FTC did not improve disease outcomes. Overall mortality was unexpectedly low.