PubMed:35294537 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/35294537","sourcedb":"PubMed","sourceid":"35294537","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/35294537","text":"Efficacy of Losartan in Hospitalized Patients With COVID-19-Induced Lung Injury: A Randomized Clinical Trial.\nIMPORTANCE: 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.\nOBJECTIVE: To test the efficacy of losartan to reduce lung injury in hospitalized patients with COVID-19.\nDESIGN, 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.\nINTERVENTIONS: Losartan 50 mg orally twice daily vs equivalent placebo for 10 days or until hospital discharge.\nMAIN 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.\nRESULTS: 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).\nCONCLUSIONS 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.\nTRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04312009.","tracks":[{"project":"maxiaofeng52_800_3","denotations":[{"id":"T10","span":{"begin":1324,"end":1332},"obj":"CI"},{"id":"T11","span":{"begin":398,"end":406},"obj":"CI"},{"id":"T12","span":{"begin":1624,"end":1632},"obj":"CI"},{"id":"T13","span":{"begin":1698,"end":1706},"obj":"CI"},{"id":"T14","span":{"begin":1835,"end":1843},"obj":"CI"},{"id":"T15","span":{"begin":2139,"end":2147},"obj":"CI"},{"id":"T16","span":{"begin":1666,"end":1673},"obj":"CI"},{"id":"T17","span":{"begin":518,"end":525},"obj":"CI"},{"id":"T18","span":{"begin":985,"end":992},"obj":"CI"},{"id":"T19","span":{"begin":1689,"end":1696},"obj":"CI"},{"id":"T20","span":{"begin":1826,"end":1833},"obj":"CI"},{"id":"T21","span":{"begin":1936,"end":1943},"obj":"CI"},{"id":"T8","span":{"begin":12,"end":20},"obj":"CI"},{"id":"T9","span":{"begin":937,"end":945},"obj":"CI"},{"id":"T22","span":{"begin":68,"end":79},"obj":"DP"},{"id":"T23","span":{"begin":224,"end":235},"obj":"DP"},{"id":"T24","span":{"begin":276,"end":287},"obj":"DP"},{"id":"T25","span":{"begin":417,"end":428},"obj":"DP"},{"id":"T26","span":{"begin":2197,"end":2208},"obj":"DP"}],"attributes":[{"subj":"T10","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T11","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T12","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T13","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T14","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T15","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T16","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T17","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T18","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T19","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T20","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T21","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T8","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T9","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T22","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T23","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T24","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T25","pred":"source","obj":"maxiaofeng52_800_3"},{"subj":"T26","pred":"source","obj":"maxiaofeng52_800_3"}]},{"project":"wangzhuo19_800_3","denotations":[{"id":"T1","span":{"begin":12,"end":20},"obj":"CI"},{"id":"T2","span":{"begin":937,"end":945},"obj":"CI"},{"id":"T3","span":{"begin":1324,"end":1332},"obj":"CI"},{"id":"T4","span":{"begin":398,"end":406},"obj":"CI"},{"id":"T5","span":{"begin":1624,"end":1632},"obj":"CI"},{"id":"T6","span":{"begin":1698,"end":1706},"obj":"CI"},{"id":"T7","span":{"begin":1835,"end":1843},"obj":"CI"},{"id":"T8","span":{"begin":2139,"end":2147},"obj":"CI"},{"id":"T9","span":{"begin":1689,"end":1696},"obj":"CI"},{"id":"T10","span":{"begin":518,"end":525},"obj":"CI"},{"id":"T11","span":{"begin":985,"end":992},"obj":"CI"},{"id":"T12","span":{"begin":1666,"end":1673},"obj":"CI"},{"id":"T13","span":{"begin":1826,"end":1833},"obj":"CI"},{"id":"T14","span":{"begin":1936,"end":1943},"obj":"CI"},{"id":"T15","span":{"begin":68,"end":79},"obj":"DP"},{"id":"T16","span":{"begin":276,"end":287},"obj":"DP"},{"id":"T17","span":{"begin":224,"end":235},"obj":"DP"},{"id":"T18","span":{"begin":417,"end":428},"obj":"DP"},{"id":"T19","span":{"begin":2197,"end":2208},"obj":"DP"}],"attributes":[{"subj":"T1","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T2","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T3","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T4","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T5","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T6","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T7","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T8","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T9","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T10","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T11","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T12","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T13","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T14","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T15","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T16","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T17","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T18","pred":"source","obj":"wangzhuo19_800_3"},{"subj":"T19","pred":"source","obj":"wangzhuo19_800_3"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"maxiaofeng52_800_3","color":"#eccd93","default":true},{"id":"wangzhuo19_800_3","color":"#b393ec"}]}]}}