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 (DEFINE-DM)

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Artery Stenosis
• Intervention / Treatment: Procedure: State-of-the-Art Percutaneous Coronary Intervention; Procedure: standard CABG

• Study Type: Interventional
• Enrollment (Estimated): 1360
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jung-hee Ham, Project manager; Phone Number: 82-2-3010-4728; Email: cvcrc5@amc.seoul.kr

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject must be ≥20 years of age with angina and/or evidence of myocardial ischemia
2. 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).
3. 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.
4. 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:

1. Unprotected left main coronary artery disease requiring revascularization
2. 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)
3. Recent ST-elevation myocardial infarction(<5 days prior to randomization)
4. Cardiogenic shock and/or need for mechanical/pharmacologic hemodynamic support
5. Severe left ventricular dysfunction (ejection fraction <30%)
6. 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
7. Contraindication or inability to take aspirin or P2Y12 inhibitors (clopidogrel, ticagrelor, or clopidogrel) for at least 6 months
8. Prior CABG
9. Extremely calcified or tortuous vessels precluding FFR measurement or intracoronary imaging evaluation
10. More than one major epicardial vessel which is chronically occluded; enrollment of 1 Chronic total occlusion lesion is allowed
11. Subjects requiring or who may require additional surgery (cardiac or noncardiac) within 1 year
12. End-stage renal disease requiring renal replacement therapy
13. Liver cirrhosis
14. Pregnant and/or lactating women.
15. Concurrent medical condition with a limited life expectancy of less than 2 years
16. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imaging- and Physiology-Guided State-of-the-Art Percutaneous Coronary Intervention	Procedure: State-of-the-Art Percutaneous Coronary Intervention; 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)
Active Comparator: Coronary-Artery Bypass Grafting	Procedure: standard CABG; Coronary-Artery Bypass Grafting

What is the study measuring?

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
Length of hospital stay		7 days
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
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

Collaborators and Investigators

• Sponsor: Duk-Woo Park, MD
• Collaborators: CardioVascular Research Foundation, Korea
• Investigators: Study Chair: Seung-jung Park, MD, Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): February 20, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 4, 2023
• First Submitted That Met QC Criteria: April 14, 2023
• First Posted (Actual): April 26, 2023

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 6, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes Mellitus; Multivessel Coronary Artery Disease; state of the art; State-of-the-Art Percutaneous Coronary Intervention; Coronary-Artery Bypass Grafting
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Diabetes Mellitus; Coronary Stenosis
• Other Study ID Numbers: AMCCV2023-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No