Covid19
Conditions
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.
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.
Interventions
DRUGFenofibrate
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)
DRUGPlacebo
Matching placebo (once/day) for 10 days
Sponsors
University of Pennsylvania
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow Mediated Dilation of the Brachial Artery | At baseline visit | Flow Mediated dilation of the brachial artery measured with ultrasound. This is a metric of endothelial function |
| Arterial Wave Reflection Magnitude | At baseline visit | Arterial wave reflection magnitude measured with high fidelity arterial tonometry and wave separation analysis |
| Large Artery Stiffness | At baseline visit | Carotid-femoral pulse wave velocity measured with arterial tonometry |
| Myocardial Function | At baseline visit | Peak longitudinal strain assessed with echocardiography. Longitudinal strain was measured as the shortening of the LV cavity longitudinal dimension (mitral annulus plane to apex) in apical echocardiographic views, expressed as the percent change relative to the end-diastolic length, where shortening is expressed as a negative change. |
| Diffusion Capacity of Lungs for Carbon Monoxide (DLCO) | At baseline visit | Diffusion capacity of lungs for carbon monoxide (DLCO) measured during pulmonary function testing |
| Aerobic Capacity | At baseline visit | Subjects will perform a maximal-effort peak oxygen consumption test using a supine bicycle exercise test with expired gas analysis. |
| Self-reported Quality of Life Via Survey | At baseline visit | Quality of life measured with the Kansas City Cardiomyopathy questionnaire (KCCQ). The overall summary score from the KCCQ ranges from 0-100, where higher scores indicate a better quality of life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fenofibrate Recipients Participants who were randomized to the Fenofibrate arm in the FERMIN trial. This drug was administered for 10 days post-randomization.
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) | 7 |
| Placebo Recipients Participants who were randomized to the placebo arm in the FERMIN trial. This drug was administered for 10 days post-randomization.
Placebo: Matching placebo (once/day) for 10 days | 5 |
| Total | 12 |
Baseline characteristics
| Characteristic | Fenofibrate Recipients | Placebo Recipients | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Continuous | 54.29 years STANDARD_DEVIATION 10.64 | 40.2 years STANDARD_DEVIATION 5.93 | 48.42 years STANDARD_DEVIATION 11.28 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United States | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 5 |
| other Total, other adverse events | 1 / 7 | 1 / 5 |
| serious Total, serious adverse events | 0 / 7 | 0 / 5 |
Outcome results
Primary
Aerobic Capacity
Subjects will perform a maximal-effort peak oxygen consumption test using a supine bicycle exercise test with expired gas analysis.
Time frame: At baseline visit
Population: 5 participants (2 fenofibrate recipients and 3 placebo recipients) did not undergo the test.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Recipients | Aerobic Capacity | 12.1 mL/min/kg |
| Placebo Recipients | Aerobic Capacity | 11.8 mL/min/kg |
Primary
Arterial Wave Reflection Magnitude
Arterial wave reflection magnitude measured with high fidelity arterial tonometry and wave separation analysis
Time frame: At baseline visit
Population: The data for 1 fenofibrate recipient were omitted from analysis due to poor quality. 1 placebo recipient did not undergo the test.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Recipients | Arterial Wave Reflection Magnitude | 43.7 % of forward wave amplitude |
| Placebo Recipients | Arterial Wave Reflection Magnitude | 42.9 % of forward wave amplitude |
Primary
Diffusion Capacity of Lungs for Carbon Monoxide (DLCO)
Diffusion capacity of lungs for carbon monoxide (DLCO) measured during pulmonary function testing
Time frame: At baseline visit
Population: The data for 2 participants (1 fenofibrate recipient and 1 placebo recipient) were omitted from analysis due to poor quality.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Recipients | Diffusion Capacity of Lungs for Carbon Monoxide (DLCO) | 23.3 mL/min/mmHg |
| Placebo Recipients | Diffusion Capacity of Lungs for Carbon Monoxide (DLCO) | 24 mL/min/mmHg |
Primary
Flow Mediated Dilation of the Brachial Artery
Flow Mediated dilation of the brachial artery measured with ultrasound. This is a metric of endothelial function
Time frame: At baseline visit
Population: The data for 1 fenofibrate recipient were omitted from analysis due to poor quality. 1 fenofibrate recipient did not undergo the test.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Recipients | Flow Mediated Dilation of the Brachial Artery | 6.1 % of brachial artery dilation |
| Placebo Recipients | Flow Mediated Dilation of the Brachial Artery | 6.2 % of brachial artery dilation |
Primary
Large Artery Stiffness
Carotid-femoral pulse wave velocity measured with arterial tonometry
Time frame: At baseline visit
Population: The data for 1 fenofibrate recipient was omitted due to poor quality. The data for 1 placebo recipient was not collected due to technical difficulty.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Recipients | Large Artery Stiffness | 5.8 m/s |
| Placebo Recipients | Large Artery Stiffness | 7 m/s |
Primary
Myocardial Function
Peak longitudinal strain assessed with echocardiography. Longitudinal strain was measured as the shortening of the LV cavity longitudinal dimension (mitral annulus plane to apex) in apical echocardiographic views, expressed as the percent change relative to the end-diastolic length, where shortening is expressed as a negative change.
Time frame: At baseline visit
Population: The data for 1 fenofibrate recipient were omitted from analysis due to poor quality. 1 placebo recipient did not undergo the test.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Recipients | Myocardial Function | -14.1 % change in length |
| Placebo Recipients | Myocardial Function | -17.9 % change in length |
Primary
Self-reported Quality of Life Via Survey
Quality of life measured with the Kansas City Cardiomyopathy questionnaire (KCCQ). The overall summary score from the KCCQ ranges from 0-100, where higher scores indicate a better quality of life.
Time frame: At baseline visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Fenofibrate Recipients | Self-reported Quality of Life Via Survey | 75.7 score on a scale |
| Placebo Recipients | Self-reported Quality of Life Via Survey | 79.7 score on a scale |