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
MD Alice Götberg, MD Robin Bouleau, MD Jacob Hollenberg, MD Mattias Ringh, RN Runa Sundelin, MD Kathleen Smith, MD Carl-Johan Treutiger, MD Thomas Nyström, MD Maria Cronhjort, MD Anders Hedman
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.
CONTRIBUTORS All authors participated in the conceptualization and planning of the study. GE, MC, MR, and AH wrote the study protocol. All authors participated in the enrolment of patients. AG, GE, RN and AH collected the data. GE performed the statistical analyses. AG wrote the first draft of the manuscript together with GE and AH. All authors contributed to the review and editing of the manuscript.
DECLARATION OF INTERESTS All authors declare that they have no conflicts of interest. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4278529 P r e p r i n t n o t p e e r r e v i e w e d This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4278529 P r e p r i n t n o t p e e r r e v i e w e d This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4278529 P r e p r i n t n o t p e e r r e v i e w e d
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