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Ramipril for the Treatment of COVID-19 (RAMIC)

Primary Purpose

COVID-19

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Ramipril 2.5 MG Oral Capsule

Placebo oral capsule

About this trial

This is an interventional treatment trial for COVID-19

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of California, San Diego

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ramipril 2.5mg orally daily

Placebo

Arm Description

Total 2.5 mg Ramipril per day once a day orally for 14 days Intervention: Ramipril

Placebo in the form of a capsule, taken orally for 14 days

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT04366050

First Posted

April 24, 2020

Last Updated

September 1, 2023

Sponsor

University of California, San Diego

Collaborators

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT04366050

Brief Title

Ramipril for the Treatment of COVID-19

Acronym

RAMIC

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

May 11, 2020 (Actual)

Primary Completion Date

May 12, 2021 (Actual)

Study Completion Date

May 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, San Diego

Collaborators

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

COVID-19

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

160 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ramipril 2.5mg orally daily

Arm Type

Experimental

Arm Description

Total 2.5 mg Ramipril per day once a day orally for 14 days Intervention: Ramipril

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo in the form of a capsule, taken orally for 14 days

Intervention Type

Drug

Intervention Name(s)

Ramipril 2.5 MG Oral Capsule

Other Intervention Name(s)

Ramipril

Intervention Description

Include description or ramipril from protocol

Intervention Type

Drug

Intervention Name(s)

Placebo oral capsule

Other Intervention Name(s)

Placebo

Intervention Description

Placebo

Primary Outcome Measure Information:

Title

Composite of Mortality or Need for ICU Admission or Ventilator Use

Description

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.

Time Frame

14 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Rohit Loomba

Organizational Affiliation

University of California, San Diego

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California, San Diego

City

La Jolla

State/Province

California

ZIP/Postal Code

92093

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

33631357

Citation

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.

Results Reference

derived

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Ramipril for the Treatment of COVID-19

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