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
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
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
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
No
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
No
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
Learn more about this trial
Ramipril for the Treatment of COVID-19
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