Covid19
Conditions
Keywords
MRI, Hyperpolarized 129Xe
Brief summary
The next phase of the COVID-19 pandemic is likely to see a surge in an associated chronic cardiopulmonary disease that will challenge health systems. Recovered patients are presenting with persistent dyspnea at the Duke Pulmonary Post-COVID clinic. Evidence is now mounting that recovered patients have significant residual pulmonary disease, while myocardial injury has also been increasingly reported. To optimally care for these patients, Duke Pulmonary study team must comprehensively assess and monitor the changes in cardiopulmonary function and relate the changes to physiologic and quality of life outcomes. The study team will deploy cutting-edge MRI to fully characterize cardiopulmonary function in enrolled 30 subjects (accrual 23 subjects) at time point 60-120 days post recovery and 6-9 months later. Cardiac MRI will assess the myocardial status and right ventricular function, while hyperpolarized 129Xe MRI will provide a 3D assessment of pulmonary ventilation, interstitial barrier integrity, and pulmonary vascular hemodynamics. The overall objective outlined in this study is to demonstrate the feasibility and value of comprehensive longitudinal imaging characterization of cardiopulmonary structure and function in patients recovered from Covid-19.
Detailed description
The proposed research builds on the established sensitivity of Hyperpolarized 129Xe MRI to obstructive and pulmonary vascular lung disease, features expected to represented in the Covid-19 cohort. It further incorporates a new understanding of the possible role of myocardial injury in these recovered patients by combining cutting-edge pulmonary and cardiac MRI. Although the initial presentation of patients with moderate to severe symptoms of COVID19 infections is dominated by respiratory symptoms, 10% go on to develop persistent post-infection symptoms which are thought to have an inflammatory etiology. Evidence suggests that pathologic activation of the inflammasome persists beyond the acute initial presentation that contributes to the persistent disabling symptoms characterized as long-haul COVID. For this trial, subjects will be eligible for enrollment if subjects are outpatients with a history of a laboratory-confirmed diagnosis of COVID-19 infection, and after 60 days or longer. The study team will accrual 13 subjects who continue to have respiratory symptoms (i.e., cough, shortness of breath, dyspnea on exertion). An additional 10 subjects engaged in competitive sports and diagnosed with COVID-19 will also be enrolled. These subjects can be asymptomatic or mildly to moderately. Although rare, cardiac impairment has been documented in \<2% of these individuals. The study team knowledge, XeMRI has not yet been studied in this specific patient subset. Existing data highlight significant racial and ethnic disparities with historically underserved minority populations (i.e., Black, LatinX) suffering disproportionately higher infection rates and more severe illness compared to Whites. This is reflected by the population enrolled in the study team RedCAP database and biorepository. As such 30% of subjects enrolled will be required to be from underserved communities.
Interventions
Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC),
Sponsors
Study design
Intervention model description
This will be a single-blinded open-label study enrolling 30 subjects (accrued 23 subjects (13 subjects who continue to have respiratory symptoms and 10 subjects within competitive sports) with a laboratory-confirmed diagnosis of COIVD-19 infection, and after 60 days or longer
Eligibility
Inclusion criteria
Diagnosis of post Coronavirus (COVID-19) Inclusion Criteria: 1. Age ≥ 18-year-old 2. Tested positive for SARS-CoV2 3. Willing and able to give informed consent and adhere to visit/protocol scheduled (consent must be given before any study procedures are performed)
Exclusion criteria
1. Prisoners 2. Pregnant, planning pregnancy, or lactating 3. Conditions that prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine). 4. Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Red Blood Cell to Membrane (RBC:M) Ratio | 1 year | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. |
| Ventilation Defect Percent | 1 year | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. |
| High Membrane Percent | 1 year | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. |
| Red Blood Cell (RBC) Defect Percent | 1 year | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. |
| Red Blood Cell to Membrane (RBC:M) Ratio at 9 Months | 9 Months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. |
| Ventilation Defect Percent at 9 Months | 9 months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. |
| High Membrane Percent at 9 Months | 9 months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. |
| Red Blood Cell (RBC) Defect Percent at 9 Months | 9 months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. |
| Identify MRI Features That Predict Physiological Outcomes With DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide) | Baseline | DLCO is the extent to which oxygen passes from the air sacs of the lungs into the blood. |
Countries
United States
Participant flow
Pre-assignment details
Historical Controls were not considered enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Participants With Diagnosis of COVID-19 (Long-hauler) 23 participants with a confirmed diagnosis of COVID-19 infection, and after 60 days or longer
Hyperpolarized 129Xenon gas: Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC), | 18 |
| Historical Controls 10 participants with historical Hyperpolarized 129Xenon imaging | 10 |
| Total | 28 |
Baseline characteristics
| Characteristic | Participants With Diagnosis of COVID-19 (Long-hauler) | Historical Controls | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 0 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 10 Participants | 25 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 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 | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 14 Participants | 8 Participants | 22 Participants |
| Region of Enrollment United States | 18 participants | 10 participants | 28 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 18 |
| other Total, other adverse events | 0 / 18 |
| serious Total, serious adverse events | 3 / 18 |
Outcome results
High Membrane Percent
To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With Diagnosis of COVID-19 (Long-hauler) | High Membrane Percent | 18.23 percentage of high membrane | Standard Deviation 29.4 |
| Historical Controls | High Membrane Percent | 0.5 percentage of high membrane | Standard Deviation 1.3 |
High Membrane Percent at 9 Months
To characterize the evolution of cardiopulmonary abnormalities over 9 months.
Time frame: 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With Diagnosis of COVID-19 (Long-hauler) | High Membrane Percent at 9 Months | 15 percentage of high membrane | Standard Deviation 30.6 |
Identify MRI Features That Predict Physiological Outcomes With DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide)
DLCO is the extent to which oxygen passes from the air sacs of the lungs into the blood.
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With Diagnosis of COVID-19 (Long-hauler) | Identify MRI Features That Predict Physiological Outcomes With DLCO (Diffusing Capacity of the Lungs for Carbon Monoxide) | 20 percentage of predicted value | Standard Deviation 8 |
Red Blood Cell (RBC) Defect Percent
To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With Diagnosis of COVID-19 (Long-hauler) | Red Blood Cell (RBC) Defect Percent | 10.6 percentage of RBC defect | Standard Deviation 5.6 |
| Historical Controls | Red Blood Cell (RBC) Defect Percent | 4.2 percentage of RBC defect | Standard Deviation 4.8 |
Red Blood Cell (RBC) Defect Percent at 9 Months
To characterize the evolution of cardiopulmonary abnormalities over 9 months.
Time frame: 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With Diagnosis of COVID-19 (Long-hauler) | Red Blood Cell (RBC) Defect Percent at 9 Months | 6.2 percentage of RBC defect | Standard Deviation 1.8 |
Red Blood Cell to Membrane (RBC:M) Ratio
To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With Diagnosis of COVID-19 (Long-hauler) | Red Blood Cell to Membrane (RBC:M) Ratio | 0.39 ratio (RBC:M) | Standard Deviation 0.14 |
| Historical Controls | Red Blood Cell to Membrane (RBC:M) Ratio | 0.51 ratio (RBC:M) | Standard Deviation 0.13 |
Red Blood Cell to Membrane (RBC:M) Ratio at 9 Months
To characterize the evolution of cardiopulmonary abnormalities over 9 months.
Time frame: 9 Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With Diagnosis of COVID-19 (Long-hauler) | Red Blood Cell to Membrane (RBC:M) Ratio at 9 Months | 0.44 ratio (RBC:M) | Standard Deviation 0.14 |
Ventilation Defect Percent
To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery.
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With Diagnosis of COVID-19 (Long-hauler) | Ventilation Defect Percent | 2.4 percentage of ventilation defect | Standard Deviation 3.5 |
| Historical Controls | Ventilation Defect Percent | 0.6 percentage of ventilation defect | Standard Deviation 0.7 |
Ventilation Defect Percent at 9 Months
To characterize the evolution of cardiopulmonary abnormalities over 9 months.
Time frame: 9 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Subjects With Diagnosis of COVID-19 (Long-hauler) | Ventilation Defect Percent at 9 Months | 0.5 percentage of ventilation defect | Standard Deviation 0.5 |