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

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

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: Placebo; Drug: Telmisartan 40mg

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii - Manoa, John A Burns School of Medicine UH Clinics at Kakaako

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo once daily
Experimental: Telmisartan; Telmisartan 40 mg po daily x 21 days	Drug: Telmisartan 40mg; Angiotensin Receptor Blocker (ARB)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Hawaii
• Collaborators: National Institute on Minority Health and Health Disparities (NIMHD)
• Investigators: Principal Investigator: Cecilia M Shikuma, MD, University of Hawaii at Manoa John A Burns School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): April 26, 2022
• Study Completion (Actual): April 26, 2022

Study Registration Dates

• First Submitted: April 21, 2020
• First Submitted That Met QC Criteria: April 22, 2020
• First Posted (Actual): April 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 16, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Telmisartan
• Other Study ID Numbers: H051; U54MD007601-34S3 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes