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Effect of Adding Losartan to Standard of Care Treatment on the Risk of Death and Icu Admission Among Hospitalized COVID-19 Patients: A Randomized Trial

22 Pages Posted: 18 Nov 2022

See all articles by Alice Götberg

Alice Götberg

Södersjukhuset (Sös) - Department of Medicine

Gustaf Edgren

Karolinska Institutet - Clinical Epidemiology Division

Robin Bouleau

Södersjukhuset (Sös) - Department of Cardiology

Jacob Hollenberg

Södersjukhuset (Sös) - Department of Cardiology

Mattias Ringh

Södersjukhuset (Sös) - Department of Cardiology

Runa Sundelin

Södersjukhuset (Sös) - Department of Cardiology

Kathleen Smith

Södersjukhuset (Sös) - Department of Infectious Diseases

Carl Johan Treutiger

Södersjukhuset (Sös) - Department of Infectious Diseases

Thomas Nyström

Karolinska Institutet - Department of Clinical Science and Education

Maria Cronhjort

Karolinska Institutet - Department of Clinical Science and Education

Anders Hedman

Södersjukhuset (Sös) - Department of Cardiology

More...

Abstract

Background: Angiotensin-converting enzyme 2 (ACE2) is the host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recognizing that angiotensin receptor blockers upregulate the expression of ACE2, it has been proposed that these drugs may have a beneficial effect in Covid-19.

Methods: We did an open-label randomized controlled trial to test whether addition of losartan to standard of care lowers the risk of death or intensive care unit (ICU) admission in patients with confirmed SARS-CoV-2 infection. The trial was run in a secondary hospital in Stockholm, Sweden between October 5th 2020 and June 21st 2021. Included patients were randomized using a 1:1 allocation ratio, to receive standard care or losartan in addition to standard care, using an electronic tool. The study was not blinded. The primary outcome was a composite of ICU admission or death within 28 days of admission.

Findings: The study was terminated for futility after a planned interim analysis. A total of 302 patients were included of whom 151 were assigned to each group. The primary outcome occurred in 12 (7·9%) in the intervention group and 17 (11·4%) in the standard-of-care group (risk difference, 3·5 percentage points; 95% confidence interval, −3·5-11). Among secondary outcomes, there were no differences between the groups in the occurrence of death (p=1·00), ICU admission (p=0·24), or the National Early Warning Scale 2 (NEWS2) score levels (p=0·15), but patients randomized to losartan treatment had a 6·7 percentage points lower risk of mechanical ventilation (95% confidence interval, 1·6-12·7) and 12·5 mg/L lower c-reactive protein concentration (95% confidence interval, 2·8-22 mg/L; p=0·01).

Interpretation: Addition of losartan to standard care treatment did not result in a lower occurrence of the primary outcome of death or ICU admission.

Trial Registration Details: ISCRTN register number: ISRCTN48734830 (2020-07-10). EudraCT number: 2020-002040-22.

Funding Information: No specific funding was acquired for the conduct of this study. Dr Edgren is supported by grants from Swedish Research Council (2017-01954), Region Stockholm (2020-0125) and clinical research appointment from Region Stockholm.

Declaration of Interests: All authors declare that they have no conflicts of interest.

Ethics Approval Statement: This was a single-center, investigator-initiated, open-label randomized controlled trial, performed at Södersjukhuset Hospital in Stockholm, Sweden. The research protocol (link to research protocol: ISRCTN48734830_Protocol_v5_22Jun2020 Alice[2103].pdf) was approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency (EudraCT number: 2020-002040-22) prior to enrolment of the first patient. The study was conducted following good clinical practice guidelines under the oversight of a data safety monitoring board. The study was designed in the spring of 2020, at a time when less data was available on the prognosis of hospitalized patients with Covid-19.

Keywords: COVID-19, losartan, angiotensin receptor blocker, ARB, hospitalized, in-hospital, SARS-CoV-2, RECOVER study, pandemic, RCT, randomized clinical trial

Suggested Citation

Götberg, Alice and Edgren, Gustaf and Bouleau, Robin and Hollenberg, Jacob and Ringh, Mattias and Sundelin, Runa and Smith, Kathleen and Treutiger, Carl Johan and Nyström, Thomas and Cronhjort, Maria and Hedman, Anders, Effect of Adding Losartan to Standard of Care Treatment on the Risk of Death and Icu Admission Among Hospitalized COVID-19 Patients: A Randomized Trial. Available at SSRN: https://ssrn.com/abstract=4278529 or http://dx.doi.org/10.2139/ssrn.4278529

Alice Götberg (Contact Author)

Södersjukhuset (Sös) - Department of Medicine ( email )

Gustaf Edgren

Karolinska Institutet - Clinical Epidemiology Division ( email )

Robin Bouleau

Södersjukhuset (Sös) - Department of Cardiology ( email )

Jacob Hollenberg

Södersjukhuset (Sös) - Department of Cardiology ( email )

Mattias Ringh

Södersjukhuset (Sös) - Department of Cardiology ( email )

Runa Sundelin

Södersjukhuset (Sös) - Department of Cardiology ( email )

Kathleen Smith

Södersjukhuset (Sös) - Department of Infectious Diseases ( email )

Carl Johan Treutiger

Södersjukhuset (Sös) - Department of Infectious Diseases ( email )

Thomas Nyström

Karolinska Institutet - Department of Clinical Science and Education ( email )

Maria Cronhjort

Karolinska Institutet - Department of Clinical Science and Education ( email )

Anders Hedman

Södersjukhuset (Sös) - Department of Cardiology ( email )

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