RAMIC: Design of a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of ramipril in patients with COVID-19

https://doi.org/10.1016/j.cct.2021.106330Get rights and content

Abstract

Background and aims

Retrospective studies have shown that angiotensin-converting-enzyme (ACE) inhibitors are associated with a reduced risk of complications and mortality in persons with novel coronavirus disease 2019 (COVID-19). Thus, we aimed to examine the efficacy of ramipril, an ACE-inhibitor, in preventing ICU admission, mechanical ventilation and/or mortality while also minimizing the risk of transmission and use of personal protective equipment (PPE).

Methods

RAMIC is a multicenter, randomized, double-blind, allocation-concealed, placebo-controlled trial comparing the efficacy of treatment with ramipril 2.5 mg orally daily compared to placebo for 14 days. The study population includes adult patients with COVID-19 who were admitted to a hospital or assessed in an emergency department or ambulatory clinic. Key exclusion criteria include ICU admission or need for mechanical ventilation at screening, use of an ACE inhibitor or angiotensin-receptor-II blocker within 7 days, glomerular filtration rate < 40 mL/min or a systolic blood pressure (BP) < 100 mmHg or diastolic BP < 65 mmHg. Patients are randomized 2:1 to receive ramipril (2.5 mg) or placebo daily. Informed consent and study visits occur virtually to minimize the risk of SARS-CoV-2 transmission and preserve PPE. The primary composite endpoint of ICU admission, invasive mechanical ventilation and death are adjudicated virtually.

Conclusions

RAMIC is designed to assess the efficacy of treatment with ramipril for 14 days to decrease ICU admission, mechanical ventilator use and mortality in patients with COVID-19 and leverages virtual study visits and endpoint adjudication to mitigate risk of infection and to preserve PPE (ClinicalTrials.gov, NCT04366050).

Keywords

SARS-CoV2
Covid-19
Mechanical ventilation
Virtual visit

Abbreviations

COVID-19
coronavirus disease 2019
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
ACEI
angiotensin-converting enzyme inhibitor
ARB
angiotensin II receptor blockers
RAAS
renin-angiotensin-aldosterone system
AKI
acute kidney injury
ITT
Intention-to-Treat
DSMB
data safety monitoring board
GFR
estimated glomerular filtration rate
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
CBC
complete blood count
CMP
comprehensive metabolic panel
FDA
Food and Drug Administration;
IND
investigational new drug.

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