Ramipril for the Treatment of COVID-19 (RAMIC)

A Randomized, Double-blind, Placebo-Controlled Trial to Evaluate the Efficacy of Ramipril to Prevent ICU Admission, Need for Mechanical Ventilation or Death in Persons With COVID-19

In this study we propose to treat 560 patients with ramipril or placebo for 14 days. After an initial evaluation for COVID-19 status, medical history, and symptom assessment, patients will receive either 2.5 mg/day of ramipril or placebo. Patients' symptoms and study endpoints will be monitored at regular intervals. After 14 days, patients will undergo a laboratory assessment and an end-of-treatment follow-up visit at day 28. The primary endpoints of successful therapy will be improved survival, reductions in ICU admissions, and/or reductions in use of mechanical ventilator support.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Placebo oral capsule; Drug: Ramipril 2.5 MG Oral Capsule

Detailed Description

Ramipril has not been studied in SARS-CoV-2 infected patients. In this study we propose to treat 560 patients with ramipril or placebo for 14 days. After an initial evaluation for COVID-19 status, medical history, and symptom assessment, patients will receive either 2.5 mg/day of ramipril or placebo. Patients' symptoms and study endpoints will be monitored at regular intervals. Additional follow-up will be performed at day 28. As an exploratory objective, biomarkers of the RAAS axis will also be monitored. The primary endpoints of successful therapy will be improved survival, reductions in ICU admissions, and/or reductions in use of mechanical ventilator support. Secondary endpoints will be the proportion of patients needing continued hospitalization, time to mortality, time to ICU admission, time to discharge from hospital, proportion of patients developing hypotension and needing pressor support, and proportion of patients developing septic shock.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Willing and able to provide written informed consent prior to performing study procedures
• Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR) test ≤ 5 days before randomization OR Clinical presentation consistent with COVID-19 infection (fever or cough or shortness of breath) with positive IgM serology
• Currently hospitalized or in an emergency department
• Peripheral capillary oxygen saturation (SpO2) ≥ 93% on room air at screening

Exclusion Criteria:

• Participation in any other clinical trial of an experimental treatment for COVID-19 (use of hydroxycholoroquine or compassionate use of choloroquine or azithromycin is allowed)
• Concurrent treatment with other agents with actual or possible direct acting antiviral activity against SARS-CoV-2 is prohibited < 24 hours prior to study drug/placebo dosing
• Requiring mechanical ventilation at screening
• Requiring ICU care at admission
• NSAID use within 12 hours of randomization or requiring continued NSAID use during this trial
• Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 X upper limit of normal (ULN)
• Estimated GFR < 40 mL/min
• History of serum creatinine ≥ 2 mg/dl in the previous 28 days
• Systolic BP < 100 mm hg or diastolic BP < 65 mm hg
• Hypersensitivity to ACEI
• History of angioedema
• Outpatient use of ACE inhibitor or Angiotensin II receptor blocker in the last 7 days
• History of renal artery stenosis
• Serum potassium ≥ 5.1 mEq/L
• Pregnancy or breastfeeding
• Use of aliskiren, amifostine, lithium, sacubitril within 7 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ramipril 2.5mg orally daily; Total 2.5 mg Ramipril per day once a day orally for 14 days Intervention: Ramipril	Drug: Ramipril 2.5 MG Oral Capsule; Include description or ramipril from protocol; Other Names: Ramipril
Placebo Comparator: Placebo; Placebo in the form of a capsule, taken orally for 14 days	Drug: Placebo oral capsule; Placebo; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of Mortality or Need for ICU Admission or Ventilator Use	The major primary outcome to be evaluated is improving a composite outcome of mortality or need for ICU admission or ventilator use within a 14-day window.	14 days

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Pfizer
• Investigators: Principal Investigator: Rohit Loomba, University of California, San Diego

Publications and helpful links

General Publications

• Ajmera V, Thompson WK, Smith DM, Malhotra A, Mehta RL, Tolia V, Yin J, Sriram K, Insel PA, Collier S, Richards L, Loomba R. RAMIC: Design of a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of ramipril in patients with COVID-19. Contemp Clin Trials. 2021 Apr;103:106330. doi: 10.1016/j.cct.2021.106330. Epub 2021 Feb 22.

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2020
• Primary Completion (Actual): May 12, 2021
• Study Completion (Actual): May 12, 2021

Study Registration Dates

• First Submitted: April 24, 2020
• First Submitted That Met QC Criteria: April 24, 2020
• First Posted (Actual): April 28, 2020

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Protease Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Ramipril
• Other Study ID Numbers: RAMIC Trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No