Evidence map›Paper›PMID 34195577›Full record

ArticleEClinicalMedicine2021

A multi-center phase II randomized clinical trial of losartan on symptomatic outpatients with COVID-19.

Michael A Puskarich, Nathan W Cummins, Nicholas E Ingraham, David A Wacker, Ronald A Reilkoff, Brian E Driver, Michelle H Biros, Fernanda Bellolio, Jeffrey G Chipman, Andrew C Nelson and 9 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EClinicalMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04311177 (Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization), which is not on this map. Cited by 45 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 6 pooled it
4.0field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04311177 phase2completednot on this map

Randomized Controlled Trial of Losartan for Patients With COVID-19 Not Requiring Hospitalization

TypeinterventionalSponsorUniversity of MinnesotaRan2020 to 2021Enrolled117ConditionsCorona Virus Infection, Acute Respiratory Distress Syndrome, SARS-CoV InfectionArmsLosartan, Placebo
3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 6 syntheses or guidelines pooled it, 67 citations in OpenAlex.

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  12. COVID-19 and cardiovascular disease in patients with chronic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024
    Review
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  14. Current drug discovery technologies · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 1 country.

Michael A PuskarichDepartment of Emergency Medicine, University of Minnesota, Minneapolis, MN, USA.
Nathan W CumminsDivision of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Nicholas E IngrahamDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
David A WackerDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Ronald A ReilkoffDivision of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Brian E DriverDepartment of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN, USA.
Michelle H BirosDepartment of Emergency Medicine, University of Minnesota, Minneapolis, MN, USA.
Fernanda BellolioDivision of Infectious Diseases, Department of Medicine, Mayo Clinic, Rochester, MN, USA.
Jeffrey G ChipmanDepartment of Surgery, University of Minnesota, Minneapolis, MN, USA.
Andrew C NelsonDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Kenneth BeckmanUniversity of Minnesota Genomics Center, University of Minnesota, Minneapolis, MN, USA.
Ryan LangloisDepartment of Microbiology and Immunology, University of Minnesota, Minneapolis, MN, USA.
Tyler BoldDivision of Infectious Diseases, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Matthew T AliotaDepartment of Veterinary and Biomedical Sciences, University of Minnesota, Twin Cities, St. Paul, MN, USA.
Timothy W SchackerDivision of Infectious Diseases, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Helen T VoelkerDepartment of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Thomas A MurrayDepartment of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Joseph S KoopmeinersDepartment of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Christopher J TignanelliDepartment of Emergency Medicine, Mayo Clinic, Rochester, MN, USA.
University of Minnesota · USMayo Clinic in Arizona · USHennepin County Medical Center · US

Funding

University of Minnesota Clinical and Translational Science Institute (UMN CTSI)UL1TR002494 · NCATS · UNIVERSITY OF MINNESOTA · PI BLAZAR, BRUCE R, WEISDORF, DANIEL J · 2018 to 2022
$34.9M
NCATS NIH HHS UL1 TR002494
6 · The paper itself

Abstract

backgroundThe SARS-CoV-2 virus enters cells via Angiotensin-converting enzyme 2 (ACE2), disrupting the renin-angiotensin-aldosterone axis, potentially contributing to lung injury. Treatment with angiotensin receptor blockers (ARBs), such as losartan, may mitigate these effects, though induction of ACE2 could increase viral entry, replication, and worsen disease.

methodsThis study represents a placebo-controlled blinded randomized clinical trial (RCT) to test the efficacy of losartan on outpatients with COVID-19 across three hospital systems with numerous community sites in Minnesota, U.S. Participants included symptomatic outpatients with COVID-19 not already taking ACE-inhibitors or ARBs, enrolled within 7 days of symptom onset. Patients were randomized to 1:1 losartan (25 mg orally twice daily unless estimated glomerular filtration rate, eGFR, was reduced, when dosing was reduced to once daily) versus placebo for 10 days, and all patients and outcome assesors were blinded. The primary outcome was all-cause hospitalization within 15 days. Secondary outcomes included functional status, dyspnea, temperature, and viral load. (clinicatrials.gov, NCT04311177, closed to new participants).

findingsFrom April to November 2020, 117 participants were randomized 58 to losartan and 59 to placebo, and all were analyzed under intent to treat principles. The primary outcome did not differ significantly between the two arms based on Barnard's test [losartan arm: 3 events (5.2% 95% CI 1.1, 14.4%) versus placebo arm: 1 event (1.7%; 95% CI 0.0, 9.1%)]; proportion difference -3.5% (95% CI -13.2, 4.8%);

interpretationIn this multicenter blinded RCT for outpatients with mild symptomatic COVID-19 disease, losartan did not reduce hospitalizations, though assessment was limited by low event rate. Importantly, viral load was not statistically affected by treatment. This study does not support initiation of losartan for low-risk outpatients.

Indexed as

Angiotensin receptor blockerCOVID-19LosartanRAAS

Identifiers

PMID34195577
PMCPMC8225661
OpenAlexW3171645706

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.