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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Covid19

Intervention / Treatment
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* Drug: Fenofibrate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Fenofibrate recipients<br>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<br>* 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)<br>* Other names: Tricor;|
| Placebo recipients<br>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<br>* Matching placebo (once/day) for 10 days<br>|

What is the study measuring?
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Primary Outcome Measures

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