Ramipril for the Treatment of COVID-19

Phase 2

Completed

Interventions: Drug: Placebo oral capsule
Drug: Ramipril 2.5 MG Oral Capsule

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo oral capsule	Placebo in the form of a capsule, taken orally for 14 days
Ramipril 2.5mg orally daily	Ramipril 2.5 MG Oral Capsule	Total 2.5 mg Ramipril per day once a day orally for 14 days Intervention: Ramipril

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures