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: Recruiting
• First Posted: April 24, 2020
• Last Update Posted: August 3, 2020
• 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)
• Estimated Enrollment: 40 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
• Estimated Primary Completion Date: June 30, 2021
• Estimated Study Completion Date: June 30, 2021

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

Contacts

Contact: Cecilia M Shikuma, MD; 808 692-1328; shikuma@hawaii.edu

Contact: Debra Ogata-Arakaki, RN; 808 692-1332; ogataara@hawaii.edu

Locations

United States, Hawaii

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

Honolulu, Hawaii, United States, 96813

Contact: Cecilia Shikuma, MD 808-692-1328 shikuma@hawaii.edu

Contact: Debra Ogata-Arakaki, RN 808 692-1332 ogataara@hawaii.edu

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: August 3, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• 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:

Telmisartan; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Molecular Mechanisms of Pharmacological Action