COVID-19
Conditions
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.
Interventions
DRUGRamipril 2.5 MG Oral Capsule
Include description or ramipril from protocol
DRUGPlacebo oral capsule
Placebo
Sponsors
Pfizer
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite of Mortality or Need for ICU Admission or Ventilator Use | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ramipril 2.5mg Orally Daily Total 2.5 mg Ramipril per day once a day orally for 14 days
Intervention: Ramipril
Ramipril 2.5 MG Oral Capsule: Include description or ramipril from protocol | 79 |
| Placebo Placebo in the form of a capsule, taken orally for 14 days
Placebo oral capsule: Placebo | 35 |
| Total | 114 |
Baseline characteristics
| Characteristic | Placebo | Total | Ramipril 2.5mg Orally Daily |
|---|---|---|---|
| Age, Continuous | 46 years STANDARD_DEVIATION 14 | 45 years STANDARD_DEVIATION 15 | 45 years STANDARD_DEVIATION 16 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 5 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 10 Participants | 7 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 30 Participants | 22 Participants |
| Race (NIH/OMB) White | 23 Participants | 67 Participants | 44 Participants |
| Sex: Female, Male Female | 20 Participants | 58 Participants | 38 Participants |
| Sex: Female, Male Male | 15 Participants | 56 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 79 | 0 / 35 |
| other Total, other adverse events | 37 / 79 | 19 / 35 |
| serious Total, serious adverse events | 2 / 79 | 0 / 35 |
Outcome results
Primary
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.
Time frame: 14 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ramipril 2.5mg Orally Daily | Composite of Mortality or Need for ICU Admission or Ventilator Use | 2 Participants |
| Placebo | Composite of Mortality or Need for ICU Admission or Ventilator Use | 0 Participants |