TY - JOUR
T1 - Ramipril for the Treatment of COVID-19
T2 - RAMIC, a Randomized, Double-Blind, Placebo-Controlled Clinical Trial
AU - Huang, Daniel Q.
AU - Ajmera, Veeral
AU - Tomaszewski, Christian
AU - LaFree, Andrew
AU - Bettencourt, Ricki
AU - Thompson, Wesley K.
AU - Smith, Davey M.
AU - Malhotra, Atul
AU - Mehta, Ravindra L.
AU - Tolia, Vaishal
AU - Yin, Jeffrey
AU - Insel, Paul A.
AU - Leachman, Stone
AU - Jung, Jinho
AU - Collier, Summer
AU - Richards, Lisa
AU - Woods, Kristin
AU - Amangurbanova, Maral
AU - Bhatt, Archana
AU - Zhang, Xinlian
AU - Penciu, Oana M.
AU - Zarich, Stuart
AU - Retta, Tamrat
AU - Harkins, Michelle S.
AU - Teixeira, J. Pedro
AU - Chinnock, Brian
AU - Utay, Netanya S.
AU - Lake, Jordan E.
AU - Loomba, Rohit
N1 - Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Healthcare Ltd., part of Springer Nature.
PY - 2023/11
Y1 - 2023/11
N2 - 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/m2. 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.
AB - 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/m2. 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.
KW - COVID-19
KW - Coronavirus
KW - Ramipril
KW - Therapy
UR - http://www.scopus.com/inward/record.url?scp=85168684909&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85168684909&partnerID=8YFLogxK
U2 - 10.1007/s12325-023-02618-7
DO - 10.1007/s12325-023-02618-7
M3 - Article
C2 - 37615850
AN - SCOPUS:85168684909
SN - 0741-238X
VL - 40
SP - 4805
EP - 4816
JO - Advances in Therapy
JF - Advances in Therapy
IS - 11
ER -