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

• ClinicalTrials.gov Identifier: NCT04360551
• Recruitment Status: Terminated
• First Posted: April 24, 2020
• Last Update Posted: July 1, 2022
• Sponsor: University of Hawaii
• Information provided by (Responsible Party): University of Hawaii

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
COVID-19	Drug: Telmisartan 40mg; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Placebo controlled trial
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 1, 2020
• Actual Primary Completion Date: April 26, 2022
• Actual Study Completion Date: April 26, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Maximum clinical severity of disease [ Time Frame: Over the 21 day period of study ]
   Based on a modified World Health Organization (WHO) COVID-19 7-point ordinal scale

Secondary Outcome Measures :

1. Incidence of treatment emergent adverse events [ Time Frame: Through study completion at day 21 of study ]
   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
2. Renin angiotensin system peptides [ Time Frame: At each study time point (day 4, day 10, day 21) ]
   Angiotensin I (AngI), AngII, Ang1-9 and Ang1-7
3. Plasma biomarkers [ Time Frame: At each study time point (day 4, day 10, day 21) ]
   plasma biomarkers of organ function/coagulation, inflammation, leukocyte chemotaxis, tissue remodeling/fibrosis and immune exhaustion by Luminex multiplexing assays such as TNF-alpha, IL-6, CK-MB, Troponin I, Fractalkine, MCP-1, PD-1, TIMP-1

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Hawaii

University of Hawaii - Manoa, John A Burns School of Medicine UH Clinics at Kakaako

Honolulu, Hawaii, United States, 96813

Sponsors and Collaborators

University of Hawaii

Investigators

• Principal Investigator: Cecilia M Shikuma, MD; University of Hawaii at Manoa John A Burns School of Medicine

More Information

• Responsible Party: University of Hawaii
• ClinicalTrials.gov Identifier: NCT04360551
• Other Study ID Numbers: H051
• First Posted: April 24, 2020
• Last Update Posted: July 1, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)

• 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

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Telmisartan; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action