Pilot Clinical Trial of the Safety and Efficacy of Telmisartan for the Mitigation of Pulmonary and Cardiac Complications in COVID-19 Patients

Study Overview
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Brief Summary
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This study will enroll 40 symptomatic outpatients tested positive for Coronavirus 2019 (COVID-19). Patients to be randomized 1:1 to Telmisartan (40 mg) vs placebo to be administered orally once daily x 21 days. Daily, the study patients will be asked to keep a record of the severity of their fever, dyspnea and fatigue and take their blood pressure (BP) and temperature. Study visits to occur on day 1 (entry), day 4, day 10 and day 21. Oro-pharyngeal swabs, and approximately 25 cc of blood will be collected at each study visit for safety labs and for the evaluation of the renin-angiotensin system (RAS) system and for various blood biomarkers of inflammation, coagulation and fibrosis.

Official Title
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Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial of the Safety and Efficacy of Telmisartan for the Mitigation of Pulmonary and Cardiac Complications in COVID-19 Patients

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Telmisartan 40mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent prior to initiation of any study procedures. Understands and agrees to comply with planned study procedures including self testing of blood pressure daily Male or non-pregnant female adult ≥18 years of age at time of enrolment. Has laboratory-confirmed severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection as determined by FDA-approved commercial or public health assay in any specimen collected ideally < 72 hours prior to randomization. Exceptions to the <72 hr inclusion criteria may be made at the discretion of the investigator. Positive for COVID-19 symptoms: fever defined as a temperature of >100.4 on study screening or self-report of daily fever at home OR shortness of breath of any degree OR fatigue causing greater than minimal interference with usual social & functional activities Women of childbearing potential must agree to use at least one primary form of contraception for the duration of the study Able to easily swallow pills Exclusion Criteria: Immediate need for hospitalization on screening Systolic blood pressure less than 100 mmHg Self-reported presence of chronic kidney disease or requiring dialysis Self-reported history of liver failure or untreated hepatitis B or C Pregnancy or breast feeding Allergy to the study medication Current use of angiotensin receptor blocker (ARB) or angiotensin converting enzyme (ACE) Inhibitor medications. Other blood pressure medications will be permitted in the systolic BP is higher than 90 mmHg Prior reaction or intolerance to ARB or ACE Inhibitor Use of aliskiren in patients with diabetes Current use of and on-going need for lithium, digoxin, potassium sparing diuretics such as spironolactone Current use of and need for potassium supplements Current or past participation in a research study within 12 weeks prior to the Screening Visit unless cleared by Study Team Inability to drive safely for study visits Subjects, who, in the opinion of the investigator, are unable to comply with the protocol evaluation, or for whom study participation may not be advisable

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan<br>Telmisartan 40 mg po daily x 21 days | Drug: Telmisartan 40mg<br>* Angiotensin Receptor Blocker (ARB)<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Clinical Severity of Disease Since Entry | We utilized the World Health Organization (WHO) COVID-19 7-point ordinal scale: 1 (not hospitalized, no limitations on activities), 2 (not hospitalized limitation on activities); 3 (hospitalized, not requiring oxygen); 4 (hospitalized and requiring oxygen); 5 (hospitalized, on non-invasive ventilation or high flow oxygen devices); 6 (hospitalized, on invasive mechanical ventilation or ECMO) and 7 (death). A symptom scale was devised to allow 'fine tuning' within the 2.0 WHO category of 'not hospitalized but limitation on activities' based on severity (no symptoms, mild, moderate, moderately severe and severe symptoms) of fever, breathing and fatigue severity scale (0 to 4 points for each factor allowing a max score of 12). A WHO scale within the '2' category was then 'fine tuned' as follows: 2.0 (</=3 symptom points), 2.25 (4-6 symptom points), 2.5 (7-9 symptom points), and 2.75 (10-12 symptom points). | maximum clinical severity of disease post entry evaluated over the 21 day clinical study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | Number of adverse events grade 2 and above utilizing the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 2014 | Through study completion at day 21 of study |