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

JAMA Netw Open. 2022 Mar 1;5(3):e222735. doi: 10.1001/jamanetworkopen.2022.2735.

Abstract

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • COVID-19 / complications*
  • COVID-19 / diagnosis
  • COVID-19 / drug therapy*
  • Double-Blind Method
  • Female
  • Hospitalization
  • Humans
  • Losartan / therapeutic use*
  • Lung Injury / diagnosis
  • Lung Injury / prevention & control*
  • Lung Injury / virology*
  • Male
  • Middle Aged
  • Organ Dysfunction Scores
  • Respiratory Function Tests
  • United States

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Losartan

Associated data

  • ClinicalTrials.gov/NCT04312009