Ramipril for the Treatment of COVID-19 (RAMIC)

• ClinicalTrials.gov Identifier: NCT04366050
• Recruitment Status: Recruiting
• First Posted: April 28, 2020
• Last Update Posted: January 20, 2021
• Sponsor: University of California, San Diego
• Collaborator: Pfizer
• Information provided by (Responsible Party): Rohit Loomba, University of California, San Diego

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Ramipril 2.5 MG Oral Capsule; Drug: Placebo oral capsule	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 560 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 11, 2020
• Estimated Primary Completion Date: May 2021
• Estimated Study Completion Date: May 2021

Arms and Interventions

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 Name: Ramipril
Placebo Comparator: Placebo; Placebo in the form of a capsule, taken orally for 14 days	Drug: Placebo oral capsule; Placebo; Other Name: Placebo

Outcome Measures

Primary Outcome Measures :

1. Composite of mortality or need for ICU admission or ventilator use [ Time Frame: 14 days ]
   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Len Lazaro; 858-822-3708; llazaro@health.ucsd.edu

Contact: Archana Bhatt; 858-822-2661; abhatt@health.ucsd.edu

Locations

United States, California

University of California, San Diego; Recruiting

La Jolla, California, United States, 92093

Contact: Len Lazaro 858-822-3708 llazaro@health.ucsd.edu

Contact: Archana Bhatt 858-822-2661 abhatt@health.ucsd.edu

Sponsors and Collaborators

University of California, San Diego

Pfizer

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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 Feb 22;103:106330. doi: 10.1016/j.cct.2021.106330. [Epub ahead of print]

• Responsible Party: Rohit Loomba, Professor of Medicine, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT04366050
• Other Study ID Numbers: RAMIC Trial
• First Posted: April 28, 2020
• Last Update Posted: January 20, 2021
• Last Verified: January 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Ramipril; Angiotensin-Converting Enzyme Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents