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- Title
Efficacy of Losartan in Hospitalized Patients With COVID-19–Induced Lung Injury: A Randomized Clinical Trial.
- 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.
- Abstract
Key Points: Question: What is the effect of losartan on lung injury in hospitalized patients with COVID-19? Findings: In this randomized clinical trial in 205 patients with evidence of COVID-19–induced acute lung injury, angiotensin receptor blockade with maximal dose losartan did not reduce lung injury at 7 days, as measured by partial pressure of oxygen to fraction of inspired oxygen ratio. Secondary outcomes, including ventilator-free days and mortality, were unaffected, but patients treated with losartan had fewer vasopressor-free days. Meaning: This randomized clinical trial found that losartan for angiotensin receptor blockade did not reduce lung injury in patients with COVID-19 and raised concerns about risks of harm. This randomized clinical trial tests the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. Importance: 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. Objective: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19. Design, Setting, and Participants: 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. Interventions: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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. Trial Registration: ClinicalTrials.gov Identifier: NCT04312009
- Subjects
UNITED States; LUNG injuries; DRUG efficacy; RESEARCH; COVID-19; RANDOMIZED controlled trials; HOSPITAL care; RESEARCH funding; STATISTICAL sampling; LOSARTAN; LONGITUDINAL method; EVALUATION
- Publication
JAMA Network Open, 2022, Vol 5, Issue 3, pe222735
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2022.2735