Diabetes-Centered Evaluation of Revascularization Strategy of Functional and Imaging-CombiNEd State-of-the-Art Percutaneous Coronary Intervention or Coronary-Artery Bypass Grafting in Patients With Diabetes Mellitus and Multivessel Coronary Artery Disease

Study Overview
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Brief Summary
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The objective of this randomized study was to compare outcomes of imaging-and physiology-guided state-of-the-art Percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG) in patients with diabetes and multivessel coronary artery disease(CAD) with left anterior descending(LAD) involvement.

Official Title
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A Comparison of Imaging- and Physiology-Guided State-of-the-Art Percutaneous Coronary Intervention and Coronary-Artery Bypass Grafting in Patients With Diabetes and Three-Vessel Coronary Artery Disease: DEFINE-DM Trial (Diabetes-Centered Evaluation of Revascularization Strategy of Functional and Imaging-CombiNEd State-of-the-Art Percutaneous Coronary Intervention or Coronary-Artery Bypass Grafting in Patients With Diabetes Mellitus and Multivessel Coronary Artery Disease)

Conditions
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Coronary Artery Stenosis

Intervention / Treatment
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* Procedure: State-of-the-Art Percutaneous Coronary Intervention
* Procedure: standard CABG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject must be ≥20 years of age with angina and/or evidence of myocardial ischemia Patients with type 2 diabetes based on the need for treatment with insulin or oral hypoglycemic drugs or a confirmed elevated blood glucose level (fasting plasma glucose elevation on >1 occasion of ≥126 mg/dL [7.0 mmol/L] or 2-h postprandial of ≥200 mg/dL [11.1 mmol/L] during oral glucose tolerance test or random plasma glucose of ≥200 mg/dL [11.1 mmol/L] with classic symptoms of hyperglycemia or hyperglycemic crisis or HbA1C ≥6.5% [48 mmol/mol]) (17). Significant multivessel CAD (defined as ≥ 50% diameter stenosis by visual estimation) of major epicardial vessels with LAD involvement and amenable to revascularization (equally suitable) by both PCI and CABG as determined by the Heart Team. The patient or guardian agrees to the study protocol and the schedule of clinical follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site. Exclusion Criteria: Unprotected left main coronary artery disease requiring revascularization The presence of complex coronary disease anatomy or lesion characteristics or other cardiac condition(s) which leads the participating interventional cardiologist to believe that PCI is not suitable (i.e. the subject should be managed with CABG or medical therapy alone) Recent ST-elevation myocardial infarction(<5 days prior to randomization) Cardiogenic shock and/or need for mechanical/pharmacologic hemodynamic support Severe left ventricular dysfunction (ejection fraction <30%) Requirement for other cardiac or non-cardiac surgical procedure (e.g., valve replacement, aorta surgery, or carotid revascularization). However, a maze procedure or pulmonary vein isolation is allowed Contraindication or inability to take aspirin or P2Y12 inhibitors (clopidogrel, ticagrelor, or clopidogrel) for at least 6 months Prior CABG Extremely calcified or tortuous vessels precluding FFR measurement or intracoronary imaging evaluation More than one major epicardial vessel which is chronically occluded; enrollment of 1 Chronic total occlusion lesion is allowed Subjects requiring or who may require additional surgery (cardiac or noncardiac) within 1 year End-stage renal disease requiring renal replacement therapy Liver cirrhosis Pregnant and/or lactating women. Concurrent medical condition with a limited life expectancy of less than 2 years Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period, except for observational registries

Ages Eligible for Study
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Minimum Age: 20 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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imaging- and Physiology-Guided State-of-the-Art Percutaneous Coronary Intervention<br> | Procedure: State-of-the-Art Percutaneous Coronary Intervention<br>* supported by intracoronary imaging (e.g., intravascular ultrasound (IVUS) or optical coherence tomography [OCT]), intracoronary physiology (e.g., fractional flow reserve [FFR] or instantaneous wave-free ratio [iFR]), contemporary metallic drug-eluting stents (DES), guideline-directed optimal medical therapy [GDMT] with advanced cardiovascular and anti-diabetic medications [e.g., a sodium-glucose cotransporter [SGLT]-2 inhibitors]) in patients with type 2 diabetes and multivessel coronary artery disease (CAD) with involvement of left anterior descending (LAD)<br>|
| Active Comparator: Coronary-Artery Bypass Grafting<br> | Procedure: standard CABG<br>* Coronary-Artery Bypass Grafting<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The event rate of major adverse cardiac or cerebrovascular events | Major adverse cardiac or cerebrovascular events (MACCE) were defined as a composite of hard clinical endpoints of death from any causes, myocardial infarction, or stroke. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The event rate of death from any cause |  | 2 years | 
| The event rate of myocardial infarction |  | 2 years | 
| The event rate of stroke |  | 2 years | 
| The event rate of composite of death from any causes, cardiovascular causes, or noncardiovascular causes |  | 2 years | 
| The event rate of myocardial infarction | any, spontaneous or procedural | 2 years | 
| The event rate of composite of death or myocardial infarction |  | 2 years | 
| The event rate of composite of death, myocardial infarction, stroke or repeat revascularization |  | 2 years | 
| The event rate of stent thrombosis | by an Academic Research Consortium (ARC) definition | 2 years | 
| The event rate of symptomatic graft occlusion or stenosis |  | 2 years | 
| The event rate of bleeding complications | BARC (Bleeding Academic Research Consortium) criteria | 2 years | 
| The event rate of periprocedural major adverse events | Periprocedural major adverse events means major arrhythmia, any unplanned surgery or therapeutic radiologic procedure, development of acute renal failure, sternal wound dehiscence, infection requiring antibiotics, prolonged intubation (>48 hours), post-pericardiotomy syndrome, etc. | 2 years | 
| Length of hospital stay |  | 7 days | 
| The event rate of rehospitalization | any, cardiac, or noncardiac causes | 7 days | 
| The change of functional class | Assessed by The Canadian Cardiovascular Society (CCS) Angina Score Classification. The minimum and maximum values are 1 and 4 respectively. A higher score of CCS angina score classification means severe exertional angina. | 1, 6, 12,18, 24 months | 
| The change of angina-related quality of life index by the Seattle Angina Questionnaire [SAQ] | The SAQ is a disease-specific patient-reported outcome (PRO) with 5 domains. The minimum and maximum values are 0 and 100 respectively. A lower score represents poor health status and a high score represents good health status. | 1, 6, 12,18, 24 months | 
| The change of angina-related quality of life index by the EQ-5D | EQ-5D is a standardised measure of health-related quality of life developed by the EuroQol Group. The minimum and maximum values are 5 and 15 respectively. A higher score of EQ-5D means a low quality of life. | 1, 6, 12,18, 24 months | 
| The number of anti-anginal medications used |  | 1, 6, 12,18, 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multivessel Coronary Artery Disease, state of the art, State-of-the-Art Percutaneous Coronary Intervention, Coronary-Artery Bypass Grafting, Diabetes Mellitus