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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| subjects with diagnosis of COVID-19 (Long-hauler) | Experimental | 23 subjects with a confirmed diagnosis of COVID-19 infection, and after 60 days or longer |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hyperpolarized 129Xenon gas | Drug | Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC), |
|
| Measure | Description | Time Frame |
|---|---|---|
| Red Blood Cell to Membrane (RBC:M) Ratio | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. | 1 year |
| Ventilation Defect Percent | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. | 1 year |
| High Membrane Percent | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. | 1 year |
| Red Blood Cell (RBC) Defect Percent | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. | 1 year |
| Red Blood Cell to Membrane (RBC:M) Ratio at 9 Months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. | 9 Months |
| Ventilation Defect Percent at 9 Months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. | 9 months |
| High Membrane Percent at 9 Months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. | 9 months |
| Red Blood Cell (RBC) Defect Percent at 9 Months |
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Diagnosis of post Coronavirus (COVID-19)
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Loretta Que, MD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duke Asthma, Allergy, and Airway Center | Durham | North Carolina | 27705 | United States |
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Historical Controls were not considered enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | Participants With Diagnosis of COVID-19 (Long-hauler) | 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), |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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), |
| BG001 | Historical Controls |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Red Blood Cell to Membrane (RBC:M) Ratio | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. | Posted | Mean | Standard Deviation | ratio (RBC:M) | 1 year |
|
9 Months
Historical Controls were not monitored/assessed for deaths and/or adverse events.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Participants With Diagnosis of COVID-19 (Long-hauler) | 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) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Loretta Que | Duke University | 919-681-8551 | loretta.que@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 26, 2021 | Feb 19, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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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
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|
To characterize the evolution of cardiopulmonary abnormalities over 9 months. |
| 9 months |
| 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. | Baseline |
10 participants with historical Hyperpolarized 129Xenon imaging |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Primary | Ventilation Defect Percent | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. | Posted | Mean | Standard Deviation | percentage of ventilation defect | 1 year |
|
|
|
| Primary | High Membrane Percent | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. | Posted | Mean | Standard Deviation | percentage of high membrane | 1 year |
|
|
|
| Primary | Red Blood Cell (RBC) Defect Percent | To determine cardiopulmonary structure-function abnormalities that characterize early phase COVID-19 recovery. | Posted | Mean | Standard Deviation | percentage of RBC defect | 1 year |
|
|
|
| Primary | Red Blood Cell to Membrane (RBC:M) Ratio at 9 Months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. | Posted | Mean | Standard Deviation | ratio (RBC:M) | 9 Months |
|
|
|
| Primary | Ventilation Defect Percent at 9 Months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. | Posted | Mean | Standard Deviation | percentage of ventilation defect | 9 months |
|
|
|
| Primary | High Membrane Percent at 9 Months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. | Posted | Mean | Standard Deviation | percentage of high membrane | 9 months |
|
|
|
| Primary | Red Blood Cell (RBC) Defect Percent at 9 Months | To characterize the evolution of cardiopulmonary abnormalities over 9 months. | Posted | Mean | Standard Deviation | percentage of RBC defect | 9 months |
|
|
|
| Primary | 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. | Posted | Mean | Standard Deviation | percentage of predicted value | Baseline |
|
|
|
| 1 |
| 18 |
| 3 |
| 18 |
| 0 |
| 18 |
| Infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Adverse event is unknown; not related to the study |
|
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |