Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial

• Published in: JAMA network open Vol. 5; no. 3; p. e222735
• Main Authors: Puskarich, Michael A, Ingraham, Nicholas E, Merck, Lisa H, Driver, Brian E, Wacker, David A, Black, Lauren Page, Jones, Alan E, Fletcher, Courtney V, South, Andrew M, Murray, Thomas A, Lewandowski, Christopher, Farhat, Joseph, Benoit, Justin L, Biros, Michelle H, Cherabuddi, Kartik, Chipman, Jeffrey G, Schacker, Timothy W, Guirgis, Faheem W, Voelker, Helen T, Koopmeiners, Joseph S, Tignanelli, Christopher J
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 16.03.2022
• Subjects: Adult; Aged; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Clinical trials; Coronaviruses; COVID-19; COVID-19 - complications; COVID-19 - diagnosis; COVID-19 Drug Treatment; Double-Blind Method; Female; Hospitalization; Humans; Infectious Diseases; Losartan - therapeutic use; Lung Injury - diagnosis; Lung Injury - prevention & control; Lung Injury - virology; Male; Middle Aged; Online Only; Organ Dysfunction Scores; Original Investigation; Respiratory Function Tests; Severe acute respiratory syndrome coronavirus 2; United States; United States
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2022.2735

SARS-CoV-2 viral entry may disrupt angiotensin II (AII) homeostasis, contributing to COVID-19 induced lung injury. AII type 1 receptor blockade mitigates lung injury in preclinical models, although data in humans with COVID-19 remain mixed. To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. This blinded, placebo-controlled randomized clinical trial was conducted in 13 hospitals in the United States from April 2020 to February 2021. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already using a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible for participation. Data were analyzed from April 19 to August 24, 2021. Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. The primary outcome was the imputed arterial partial pressure of oxygen to fraction of inspired oxygen (Pao2:Fio2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity; days without supplemental o2, ventilation, or vasopressors; and mortality. Losartan pharmacokinetics and RAAS components (AII, angiotensin-[1-7] and angiotensin-converting enzymes 1 and 2)] were measured in a subgroup of participants. A total of 205 participants (mean [SD] age, 55.2 [15.7] years; 123 [60.0%] men) were randomized, with 101 participants assigned to losartan and 104 participants assigned to placebo. Compared with placebo, losartan did not significantly affect Pao2:Fio2 ratio at 7 days (difference, -24.8 [95%, -55.6 to 6.1]; P = .12). Compared with placebo, losartan did not improve any secondary clinical outcomes and led to fewer vasopressor-free days than placebo (median [IQR], 9.4 [9.1-9.8] vasopressor-free days vs 8.7 [8.2-9.3] vasopressor-free days). This randomized clinical trial found that initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury did not improve Pao2:Fio2 ratio at 7 days. These data may have implications for ongoing clinical trials. ClinicalTrials.gov Identifier: NCT04312009.