Ramipril for the Treatment of COVID-19: RAMIC, a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Daniel Q. Huang, NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
Veeral Ajmera, NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
Christian Tomaszewski, Department of Emergency Medicine, University of California, San Diego and the El Centro Regional Medical Center, San Diego, CA, USA.
Andrew LaFree, Department of Emergency Medicine, University of California, San Diego and the El Centro Regional Medical Center, San Diego, CA, USA.
Ricki Bettencourt, NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
Wesley K. Thompson, Division of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA.
Davey M. Smith, Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Atul Malhotra, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Ravindra L. Mehta, Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Vaishal Tolia, Department of Emergency Medicine, University of California San Diego, La Jolla, CA, USA.
Jeffrey Yin, Department of Pharmacy, University of California San Diego, La Jolla, CA, USA.
Paul A. Insel, Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
Stone Leachman, NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
Jinho Jung, NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
Summer Collier, Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, CA, USA.
Lisa Richards, NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
Kristin Woods, Clinical & Translational Research Institute, University of California, San Diego, La Jolla, CA, USA.
Maral Amangurbanova, NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA.
Archana Bhatt, Clinical & Translational Research Institute, University of California, San Diego, La Jolla, CA, USA.
Xinlian Zhang, Division of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health, University of California San Diego, San Diego, CA, USA.
Oana M. Penciu, Beverly Hospital, Montebello, CA, USA.
Stuart Zarich, Section of Cardiovascular Medicine, Yale New Haven Health Bridgeport Hospital, Bridgeport, CT, USA.
Tamrat Retta, Department of Internal Medicine, Howard University, Washington, DC, USA.
Michelle S. Harkins, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
J Pedro Teixeira, Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
Brian Chinnock, Department of Emergency Medicine, University of California San Francisco-Fresno Medical Education Program, Fresno, CA, USA.
Netanya S. Utay, Division of Infectious Diseases and Geographic Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jordan E. Lake, Division of Infectious Diseases, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center, Houston, TX, USA.
Rohit Loomba, NAFLD Research Center, Division of Gastroenterology, University of California at San Diego, La Jolla, CA, USA. roloomba@ucsd.edu.

Document Type

Article

Publication Title

Advances in therapy

Abstract

INTRODUCTION: Retrospective studies report that angiotensin-converting enzyme inhibitors (ACEIs) may reduce the severity of COVID-19, but prospective data on de novo treatment with ACEIs are limited. The RAMIC trial was a randomized, multicenter, placebo-controlled, double-blind, allocation-concealed clinical trial to examine the efficacy of de novo ramipril versus placebo for the treatment of COVID-19. METHODS: Eligible participants were aged 18 years and older with a confirmed diagnosis of SARS-CoV-2 infection, recruited from urgent care clinics, emergency departments, and hospital inpatient wards at eight sites in the USA. Participants were randomly assigned to daily ramipril 2.5 mg or placebo orally in a 2:1 ratio, using permuted block randomization. Analyses were conducted on an intention-to-treat basis. The primary outcome was a composite of mortality, intensive care unit (ICU) admission, or invasive mechanical ventilation by day 14. RESULTS: Between 27 May 2020 and 19 April 2021, a total of 114 participants (51% female) were randomized to ramipril (n = 79) or placebo (n = 35). The overall mean (± SD) age and BMI were 45 (± 15) years and 33 (± 8) kg/m. Two participants in the ramipril group required ICU admission and one died, compared with none in the placebo group. There were no significant differences between ramipril and placebo in the primary endpoint (ICU admission, mechanical ventilation, or death) (3% versus 0%, p = 1.00) or adverse events (27% versus 29%, p = 0.82). The study was terminated early because of a low event rate and subsequent Emergency Use Authorization of therapies for COVID-19. CONCLUSION: De novo ramipril was not different compared with placebo in improving or worsening clinical outcomes from COVID-19 but appeared safe in non-critically ill patients with COVID-19. TRIAL REGISTRATION: Clinicaltrials.gov NCT04366050.

First Page

4805

Last Page

4816

DOI

10.1007/s12325-023-02618-7

Publication Date

11-1-2023

Identifier

37615850 (pubmed); NIHMS1928648 (mid); PMC10709987 (pmc); 10.1007/s12325-023-02618-7 (doi); 10.1007/s12325-023-02618-7 (pii)

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