Cardiovascular, Pulmonary, and Integrative Functional Phenotypes in COVID-19 Survivors - Effect of Fenofibrate

• ClinicalTrials.gov Identifier: NCT05080192
• Recruitment Status: Recruiting
• First Posted: October 15, 2021
• Last Update Posted: October 19, 2022
• Sponsor: University of Pennsylvania
• Information provided by (Responsible Party): University of Pennsylvania

Study Description

Brief Summary:

The International multicenter FEnofibRate as a Metabolic INtervention for COVID-19 (FERMIN) trial is being executed. The trial is testing a short intervention (10 days of fenofibrate therapy) on 30-day outcomes in COVID-19. The overarching goal of this sub-study is to explore the impact of fenofibrate on key longer term phenotypes of vascular, cardiac and pulmonary health, integrated cardiopulmonary function, persistent/chronic symptoms and quality of life.

Condition or disease	Intervention/treatment
Covid19	Drug: Fenofibrate; Drug: Placebo

Detailed Description:

The International multicenter FEnofibRate as a Metabolic INtervention for COVID-19 (FERMIN) trial is being executed. The aim of this trial is to assess the impact of fenofibrate (administered for 10 days) to improve clinical outcomes in patients with COVID-19, assessed at 30 days. However, given the accumulating evidence of chronic / long term sequelae of COVID-19, it is important to assess the long-term impact of this intervention in this patient population. The overarching goal of this substudy is to assess the impact of fenofibrate on key intermediate phenotypes of vascular, cardiac and pulmonary health. We also aim to address the impact of fenofibrate therapy (administered during the acute COVID-19 episode as part of the parent FERMIN trial) on long-term integrated cardiopulmonary function, persistent/chronic symptoms and quality of life. We will accomplish this via enrollment of previous FERMIN participants from the University of Pennsylvania, in an phenotyping study designed to assess vascular, cardiac and pulmonary status several months after the index episode of COVID-19. We will perform these assessments ~6 months after initial randomization, among 40 FERMIN trial participants enrolled at the University of Pennsylvania.

Study Design

• Study Type: Observational
• Estimated Enrollment: 40 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Cardiovascular, Pulmonary, and Integrative Functional Phenotypes in COVID-19 - Effect of Fenofibrate
• Actual Study Start Date: February 26, 2021
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: December 31, 2024

Groups and Cohorts

Group/Cohort	Intervention/treatment
Fenofibrate recipients; Approximately 20 subjects who were randomized to the Fenofibrate arm in the FERMIN trial. This drug was administered for 10 days post-randomization.	Drug: Fenofibrate; 145 mg/d of Tricor (administered as part of the parent FERMIN trial) for 10 days, or renal corrected dose equivalent (depending on renal function); Other Name: Tricor
Placebo recipients; Approximately 20 subjects who were randomized to the placebo arm in the FERMIN trial. This drug was administered for 10 days post-randomization.	Drug: Placebo; Matching placebo (once/day) for 10 days

Outcome Measures

Primary Outcome Measures :

1. Flow Mediated dilation of the brachial artery [ Time Frame: ~6 months ]
   Flow Mediated dilation of the brachial artery measured with ultrasound. This is a metric of endothelial function
2. Arterial wave reflection magnitude [ Time Frame: ~6 months ]
   Arterial wave reflection magnitude measured with high fidelity arterial tonometry and wave separation analysis
3. Large Artery Stiffness [ Time Frame: ~6 months ]
   Carotid-femoral pulse wave velocity measured with arterial tonometry
4. Myocardial function [ Time Frame: ~6 months ]
   Peak longitudinal strain assessed with echocardiography
5. Diffusion capacity of lungs for carbon monoxide (DLCO) [ Time Frame: ~6 months ]
   Diffusion capacity of lungs for carbon monoxide (DLCO) measured during pulmonary function testing
6. Aerobic capacity [ Time Frame: ~6 months ]
   Measured as Peak oxygen consumption during a cardiopulmonary exercise test
7. Quality of life [ Time Frame: ~6 months ]
   Quality of life measured with the Kansas City Cardiomyopathy questionnaire

Biospecimen Retention:   Samples With DNA

Plasma, urine, breath condensate, buffy coat, endothelial cells and RNA will be collected from study subjects

Eligibility Criteria

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

Study Population

Patients will be screened from our FERMIN trial population. Participants will be approached by a member of the study team for participation. Participants will undergo a comprehensive assessment of key phenotypes (6±3 months after the index COVID-19 episode).

Criteria

Inclusion Criteria:

• Having been eligible, enrolled and randomized in the parent FERMIN trial, completing all study procedures up to the 30-day time point (as specified in the parent protocol).

Exclusion Criteria

• Prisoners/incarcerated individuals;
• Pregnancy (potentially eligible patients of reproductive age will undergo a pregnancy test). This exclusion is due to the fact that pregnancy may confound the various cardiopulmonary phenotypes assessed in this study
• Inability to provide informed consent.
• History of cardiovascular disease (defined as heart failure, myocardial infarction, coronary revascularization, serious arrhythmia, stroke, or peripheral artery disease), glomerular disease or polycystic kidney disease prior to the index COVID-19 episode.
• Estimated glomerular filtration rate <30 mL/min/1.73m2 prior to the index COVID-19 episode.

Contacts and Locations

Contacts

Contact: Julio A Chirinos, MD, PhD; 215-200-7779; julio.chirinos@pennmedicine.upenn.edu

Contact: Katherine Greene, MPH; 215-662-7580; katherine.greene@pennmedicine.upenn.edu

Locations

United States, Pennsylvania

University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Julio A Chirinos, MD, PhD 215-200-7779 julio.chirinos@pennmedicine.upenn.edu

Contact: Katherine J Greene, MPH 215-662-7580 katherine.greene@pennmedicine.upenn.edu

Principal Investigator: Julio A Chirinos, MD, PhD

Principal Investigator: Jordana B Cohen, MD, MSCE

Sub-Investigator: Benjamin A Abramoff, MD, MS

Sub-Investigator: Robert M Kotloff, MD

Sub-Investigator: Nadine Al-Naamani, MD

Sub-Investigator: Franklin Caldera, DO

Sub-Investigator: Matthew C Hyman, MD, PhD

Sub-Investigator: Rajat Deo, MD

Sub-Investigator: Nathaniel C Reisinger, MD

Sub-Investigator: Mark Kahn, MD

Sponsors and Collaborators

University of Pennsylvania

More Information

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT05080192
• Other Study ID Numbers: 844349
• First Posted: October 15, 2021
• Last Update Posted: October 19, 2022
• Last Verified: October 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

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; Fenofibrate; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents