COVID-19Phase 2RAMICNCT04366050
Ramipril for the Treatment of COVID-19
A Phase 2 study testing Ramipril 2.5 MG Oral Capsule in people with COVID-19, run by University of California, San Diego at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Ramipril 2.5 MG Oral Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteUnited States
- Study dates
- 11 May 2020to 12 May 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Diego
La Jolla, California, 92093
About this study
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
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.
Read the 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.
- Conditions
- COVID-19
- Being tested
- Ramipril 2.5 MG Oral Capsule, Placebo oral capsule
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ramipril 2.5 MG Oral CapsuleDrug
Also called Ramipril
Include description or ramipril from protocol
Placebo oral capsuleDrug
Also called Placebo
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Ramipril 2.5mg orally daily | Experimental | Total 2.5 mg Ramipril per day once a day orally for 14 days
Intervention: Ramipril Receives: Drug: Ramipril 2.5 MG Oral Capsule |
| Placebo | Placebo comparator | Placebo in the form of a capsule, taken orally for 14 days Receives: Drug: Placebo oral capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2020
- Study start11 May 2020
- Primary completion12 May 2021
- Study completion12 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Rohit Loomba, University of California, San Diego
- Investigators
- Rohit Loomba, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04366050
- Sponsor's protocol ID
- RAMIC Trial
- Acronym
- RAMIC
- Status last verified
- Sep 2023
- First submitted
- 24 Apr 2020
- Last updated
- 28 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Huang DQ, Ajmera V, Tomaszewski C, LaFree A, Bettencourt R, Thompson WK, Smith DM, Malhotra A, Mehta RL, Tolia V, Yin J, Insel PA, Leachman S, Jung J, Collier S, Richards L, Woods K, Amangurbanova M, Bhatt A, Zhang X, Penciu OM, Zarich S, Retta T, Harkins MS, Teixeira JP, Chinnock B, Utay NS, Lake JE, Loomba R. Ramipril for the Treatment of COVID-19: RAMIC, a Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Adv Ther. 2023 Nov;40(11):4805-4816. doi: 10.1007/s12325-023-02618-7. Epub 2023 Aug 24.
PubMed 37615850Ajmera 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.
PubMed 33631357
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04366050
- Acronym / sponsor ID
- RAMIC / RAMIC Trial
- Conditions
- COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- 11 May 2020 (actual)
- Primary completion
- 12 May 2021 (actual)
- Study completion
- 12 May 2021 (actual)
- First posted
- 28 Apr 2020 (actual)
- Results
- Posted 28 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ramipril 2.5mg orally daily | Experimental | Drug: Ramipril 2.5 MG Oral CapsuleTotal 2.5 mg Ramipril per day once a day orally for 14 days Intervention: Ramipril |
| Placebo | Placebo comparator | Drug: Placebo oral capsulePlacebo in the form of a capsule, taken orally for 14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ramipril 2.5 MG Oral CapsuleAlso: RamiprilInclude description or ramipril from protocol | Drug | Ramipril 2.5mg orally daily |
| Placebo oral capsuleAlso: PlaceboPlacebo | Drug | Placebo |
Primary outcome
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37615850Huang DQ, Ajmera V, Tomaszewski C, LaFree A, Bettencourt R, Thompson WK, Smith DM, Malhotra A, Mehta RL, Tolia V, Yin J, Insel PA, Leachman S, Jung J, Collier S, Richards L, Woods K, Amangurbanova M, Bhatt A, Zhang X, Penciu OM, Zarich S, Retta T, Harkins MS, Teixeira JP, Chinnock B, Utay NS, Lake JE, Loomba R. Ramipril for the Treatment of COVID-19: RAMIC, a Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Adv Ther. 2023 Nov;40(11):4805-4816. doi: 10.1007/s12325-023-02618-7. Epub 2023 Aug 24.
- Derived from this study: PubMed 33631357Ajmera 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.
Related trials for COVID-19
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Active, not recruiting
Intervention to Address Disparate Mental Health Consequences of COVID-19 Pandemic on Latinx and African Newcomers
Mental Health Issue, Mental Health Disorder
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rohit Loomba principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ramipril 2.5 MG Oral Capsule in people with COVID-19, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composite of Mortality or Need for ICU Admission or Ventilator Use (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04366050, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.