Early Revascularization in Stable Ischemic Heart Disease Using P.E.T. Imaging

Study Overview
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Brief Summary
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To compare the impact of revascularization and Optimal Medical Treatment (OMT) on the extent of severely reduced coronary flow capacity in stable ischemic heart disease.

Detailed Description
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The initial Positron Emission Tomography (PET) scan will be performed as part of clinical practice. If the patient is a potential candidate for the study, the patient will be screened for inclusion and exclusion criteria. After being informed about the study potential risks, all patients giving written informed consent will be randomized into one of two groups: Urgent revascularization combined with Optimal Medical Treatment (OMT) or OMT with delayed revascularization. Following the initial PET scan, randomization and treatment, each group will undergo a second PET scan at the 3-4 month mark and a third PET scan at the one year mark. Some crossover may occur with the two groups. The OMT without urgent revascularization patients will remain in that group, if clinically stable, up to three months. At their first follow-up visit (Day 105±20), patients will be offered the option of continued medical treatment or elective revascularization consistent with informed patient preference and clinical judgement. Patients, in consultation with their physicians, may elect to undergo revascularization at any time thereafter.

Official Title
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A Prospective, Randomized Trial of Early Revascularization in Stable Ischemic Heart Disease Guided by Positron Emission Tomography of Artery Specific Integrated Comprehensive Quantitative Myocardial Perfusion

Conditions
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Ischemic Heart Disease

Intervention / Treatment
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* Procedure: Revascularization by Coronary Artery Bypass Graft or Percutaneous Coronary Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Stable ischemic heart disease as determined by an investigator. Areas of severely reduced CFC or relative stress images on the Rentrop diagnostic PET MPI consistent with clinical judgement as follows: • PETs with a defect on rest relative images of ≤60% of max for ≤5% of LV (no large scar) plus: i. ≥2% of LV with CFCblue* or ii. ≥10% of LV with CFCgreen* plus at least one pixel with CFCblue* *CFCblue is defined as a dipyridamole induced stress flow ≤ 0.83 ml/min/g of myocardium and a CFR ≤ 1.27. CFCgreen is defined as a dipyridamole induced stress flow ≤1.09 and >0.83 ml/min/g of myocardium and a CFR ≤1.60 and >1.27. Willing to comply with the follow-up schedule of the trial. Subject must sign the informed consent in English or Spanish. Exclusion Criteria: Any conditions that may compromise or prevent the necessary imaging requirements. Less than one-year life expectancy. Currently pregnant or planning to become pregnant during the course of the study. Any other issues that the Investigator believes may interfere with treatment or follow-up. Subjects who lack capacity to consent for themselves.

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: After randomization, patients will receive urgent revascularization combined with Optimal Medical Treatment or Optimal Medical Treatment with delayed revascularization. Following the initial PET scan, randomization and treatment, each group will undergo a second PET scan at the 3-4 month mark and a third PET scan at the one year mark. At their first follow-up visit (3-4 month mark), patients in the OMT with delayed revascularization group will be offered the option of continued medical treatment or elective revascularization consistent with informed patient preference and clinical judgement. Patients, in consultation with their physicians, may elect to undergo revascularization at any time thereafter.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Urgent revascularization with Optimal Medical Therapy<br>Revascularization will be performed via either Percutaneous Coronary Intervention or Coronary Artery Bypass Graft, and the selection of the specific procedure will be at the discretion of the patient and their physician(s). Patients will be followed for one year after randomization. Follow-up visits will occur at Baseline, Day 105, and Day 365. At each visit, a rest-stress PET assessment will be performed, and adverse events related to study procedures and cardiac disease will be captured. | Procedure: Revascularization by Coronary Artery Bypass Graft or Percutaneous Coronary Intervention<br>* Urgent revascularization via CABG or PCI combined with Optimal Medical Treatment<br>|
| Other: Optimal Medical Treatment with delayed revascularization<br>OMT without revascularization for a minimum of approximately 105 days if clinically stable. At their first follow-up visit (Day 105±20), patients will be offered the option of continued medical treatment or elective revascularization consistent with informed patient preference and clinical judgement. Patients, in consultation with their physicians, may elect to undergo revascularization at any time thereafter and will be followed for one year after randomization. Follow-up visits will occur at Baseline, Day 105, and Day 365. At each visit, a rest-stress PET assessment will be performed, and adverse events related to study procedures and cardiac disease will be captured. | Procedure: Revascularization by Coronary Artery Bypass Graft or Percutaneous Coronary Intervention<br>* Urgent revascularization via CABG or PCI combined with Optimal Medical Treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in the % of left ventricle (LV) with Coronary Flow Capacity (CFC)blue. | CFCblue is defined as a dipyridamole induced stress flow ≤ 0.83 ml/min/g of myocardium and a CFR ≤ 1.27. | Baseline and Day 105+20 | 
| Change from baseline in the % of left ventricle (LV) with Coronary Flow Capacity (CFC)green. | CFCgreen is defined as a dipyridamole induced stress flow ≤1.09 and >0.83 ml/min/g of myocardium and a CFR ≤1.60 and >1.27. | Baseline and Day 105+20 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in % of LV with CFCblue. | Change in % in Left Ventricle with Coronary Flow Capacity blue. | Baseline and Day 105 +20 and Day 365+30 | 
| Change in % of LV with CFCgreen. | Change in % of Left Ventricle with Coronary Flow Capacity green. | Baseline and Day 105 +20 and Day 365+30 | 
| Change in CFC histogram distribution. | Change in Coronary Flow Capacity histogram distribution. | Baseline and Day 105 +20 and Day 365+30 | 
| Change in minimum quadrant average CFR. | Change in minimum quadrant average Coronary Flow Reserve. | Baseline and Day 105 +20 and Day 365+30 | 
| Change in minimum quadrant average stress ml/min/g. | Minimum quadrant average stress changes during PET. | Baseline and Day 105 +20 and Day 365+30 | 
| Change in minimum stress relative quadrant average. | Change in relative minimum uptake on stress images. | Baseline and Day 105 +20 and Day 365+30 | 
| Change in global CFR. | Change in global Coronary Flow Reserve. | Baseline and Day 105 +20 and Day 365+30 | 
| Change in specific iso-contour defect size & its average CFR. | Change in specific iso-contour defect size & its average Coronary Flow Reserve. | Baseline and Day 105 +20 and Day 365+30 | 
| Change in DEFECT stress ml/min/g. | Change of absolute flow in ml/min/g in the defect during stress. | Baseline and Day 105 +20 and Day 365+30 | 
| Change in DEFECT relative stress. | Change in size and severity of stress induced perfusion defects during stress. | Baseline and Day 105 +20 and Day 365+30 | 
| Changes in an additional 120 PET flow fields. | Changes in 120 PET flow fields derived in the CORE lab comparing Rentrop PETs with reprocessed PETs at University of Texas Health Science Center Houston | Baseline and Day 105 +20 and Day 365+30 | 
| Rate of adverse events | Rate of major adverse cardiovascular events (defined as death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest). | Baseline and Day 105 +20 and Day 365+30 | 
| Rate of safety events. | Rate of safety events during the course of the trial such as death or adverse effects. | Baseline and Day 105 +20 and Day 365+30 | 
| Rate of procedure-related adverse events | Rate of procedure-related adverse events such as death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. | Baseline and Day 105 +20 and Day 365+30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Positron Emission Tomography, PET scan