Randomized Prospective Open Label Study Shows No Impact on Clinical Outcome of Adding Losartan to Hospitalized COVID-19 Patients with Mild Hypoxemia

INTRODUCTION: Despite considerable scientific debate, there have been no prospective clinical studies on the effects of angiotensin II receptor blockers (ARBs) on the course of COVID-19 infection. Losartan is the ARB that was chosen to be tested in this study. METHODS: Patients with COVID-19 and mild hypoxia (receipt of ≤ 3 L/min O(2) by nasal cannula) admitted to three hospitals were randomized in a 1:1 ratio within 72 h of SARS-CoV-2 nucleic acid testing confirmation to prospectively receive standard of care (SOC) alone or SOC plus losartan 12.5 mg orally every 12 h for 10 days or until hospital discharge, with the option to titrate upward dependent on blood pressure tolerability. Primary composite endpoint was receipt of mechanical ventilation or death before receiving ventilation. Subjects were followed until discharge to home or until an endpoint was met in the hospital. RESULTS: Sixteen subjects received an ARB plus SOC and 15 subjects received SOC alone. The median age was 53 years for both groups. Median time from hospital admission to study enrollment was 2 days (range 1–6) for the ARB group and 2 days (range 1–4) for the SOC group. Mean Charlson comorbidity index was 2 for both groups. One subject in each group achieved the composite endpoint. CONCLUSION: This small prospective randomized open-label study showed no clinically significant impacts of ARB therapy in mildly hypoxemic patients hospitalized with COVID-19 early in the pandemic. A larger prospective randomized placebo-controlled trial would be needed to confirm these findings or capture less pronounced effects and probably should focus on outpatients earlier in disease course. TRIAL REGISTRATION: clinicaltrials.gov; March 27, 2020; NCT04340557.