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 three-vessel CAD (not involving left main).

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Stenosis
• Intervention / Treatment: Procedure: standard CABG; Procedure: State-of-the-Art Percutaneous Coronary Intervention

• Study Type: Interventional
• Enrollment (Estimated): 1500
• Phase: Not Applicable

Contacts and Locations

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

Study Locations

• China
  • Beijing, China
    • Not yet recruiting
    • Fuwai Hospital, Chinese Academy of Medical Sciences (CAMS)
    • Contact: Kefei Dou, MD
    • Principal Investigator: Kefei Dou, MD
  • Hanzhou, China
    • Recruiting
    • Second Affiliated Hospital of Zhejiang University School of Medicine
    • Contact: Jian'an Wang, MD
    • Principal Investigator: Jian'an Wang, MD
• India
  • Gurugram, India
    • Recruiting
    • Medanta - The Medicity
    • Contact: Rajneesh Kapoor, MD
    • Principal Investigator: Rajneesh Kapoor, MD
  • New Delhi, India
    • Not yet recruiting
    • Fortis Escorts Heart Institute
    • Contact: Ashok Seth, MD
    • Principal Investigator: Ashok Seth, MD
• Malaysia
  • Kota Samarahan, Malaysia
    • Recruiting
    • Sarawak Heart Centre
    • Contact: Alan Pong, MD
    • Principal Investigator: Alan Pong, MD
• Serbia
  • Belgrade, Serbia
    • Not yet recruiting
    • University Clinical Center of Serbia
    • Contact: Branko Beleslin, MD
    • Principal Investigator: Branko Beleslin, MD
• Singapore
  • Singapore, Singapore
    • Not yet recruiting
    • National Heart Centre Singapore (NHCS)
    • Contact: Tan Wei Chieh Jack, MD
    • Principal Investigator: Tan Wei Chieh Jack, MD
• South Korea
  • Daegu, South Korea
    • Recruiting
    • Keimyung University Dongsan Medical Center
    • Contact: Chul-hyun Lee, MD
    • Principal Investigator: Chul-hyun Lee, MD
  • Daegu, South Korea
    • Not yet recruiting
    • Daegu Catholic University Medical Center
    • Principal Investigator: Jin-bae Lee, MD
    • Contact: Jin-bae Lee, MD
  • Daegu, South Korea
    • Not yet recruiting
    • Yeungnam University Medical Center
    • Principal Investigator: Woong Kim, MD
    • Contact: Woong Kim, MD
  • Daejeon, South Korea
    • Not yet recruiting
    • Chungnam national university hospital
    • Contact: Jin-ok Jeong, MD
    • Principal Investigator: Jin-ok Jeong, MD
  • Daejeon, South Korea
    • Withdrawn
    • Konyang University Hospital
  • Gangneung, South Korea
    • Not yet recruiting
    • GangNeung Asan Hospital
    • Contact: Han-bit Park, MD
    • Principal Investigator: Han-bit Park, MD
  • Gwangju, South Korea
    • Recruiting
    • Chonnam National University Hospital
    • Contact: Young-keun Ahn, MD
    • Principal Investigator: Young-keun Ahn, MD
  • Ilsan, South Korea
    • Recruiting
    • National Health Insurance Service Ilsan Hospital
    • Contact: Ji-yong Jang, MD
    • Principal Investigator: Ji-yong Jang, MD
  • Incheon, South Korea
    • Not yet recruiting
    • Gachon University Gil Hospital
    • Principal Investigator: Seung-hwan Han, MD
    • Contact: Seung-hwan Han, MD
  • Pusan, South Korea
    • Recruiting
    • Dong-A Medical Center
    • Principal Investigator: Yong-rak Cho, MD
    • Contact: Yong-rak Cho, MD
  • Seoul, South Korea
    • Recruiting
    • Samsung Medical Center
    • Contact: Joo-yong Han, MD
    • Principal Investigator: Joo-yong Han, MD
  • Seoul, South Korea
    • Recruiting
    • Asan Medical Center
    • Contact: Duk-woo Park, MD
    • Principal Investigator: Duk-woo Park, MD
  • Seoul, South Korea
    • Not yet recruiting
    • Hanyang University Seoul Hospital
    • Contact: Young-hyo Lim, MD
    • Principal Investigator: Young-hyo Lim, MD
  • Seoul, South Korea
    • Not yet recruiting
    • SNU Boramae Medical Center
    • Contact: Sang-hyun Kim, MD
    • Principal Investigator: Sang-hyun Kim, MD
  • Suwon, South Korea
    • Not yet recruiting
    • The Catholic university of Korea, St. Vincent's Hospital
    • Contact: Sung-ho Hur, MD
    • Principal Investigator: Sung-ho Hur, MD
  • Uijeongbu-si, South Korea
    • Recruiting
    • The Catholic University of Korea, Uijeongbu St. Mary's Hospital
    • Contact: Hyo-seok Ahn, MD
    • Principal Investigator: Hyo-seok Ahn, MD
  • Ulsan, South Korea
    • Recruiting
    • Ulsan University Hospital
    • Contact: Eun-seok Shin, MD
    • Principal Investigator: Eun-seok Shin, MD
• Taiwan
  • Taipei, Taiwan
    • Not yet recruiting
    • National Taiwan University Hospital
    • Contact: Paul Hsien Li Kao, MD
    • Principal Investigator: Paul Hsien Li Kao, MD
• Thailand
  • Bangkok, Thailand
    • Recruiting
    • Siriraj Hospital
    • Contact: Karokoth Towashiraporn, MD
    • Principal Investigator: Karokoth Towashiraporn, MD
• United States
  • California
    • Palo Alto, California, United States, 94304
      • Not yet recruiting
      • Palo Alto VA Medical Center
      • Contact: Fearon F. William, MD
      • Principal Investigator: Fearon F. William, MD

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]).
3. Significant three-vessel CAD (defined as ≥ 50% diameter stenosis [DS] by visual estimation in each of the three major epicardial vessels or major side branches but not involving the left main coronary artery) and equivalently amenable to revascularization by means of either PCI or CABG as determined by the Heart Team at the trial site.
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.
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 prasugrel) 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. However, where at least one or more conditions are satisfied, it could be an exception according to an investigator's discretion;

1) Participated in the observational study expected no effect on the safety and/or effectiveness evaluation of this trial.

2) Screening failed before any interventional factor is involved.

3) Participated in academic trials like strategic comparison studies conducted under standard therapy provided that there is no additional risk or a specific procedure to a subject and no interference between this trial and other studies.

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 DES (durable polymer everolimus-eluting stents; XIENCE family stent system, Abbott Vascular), guideline-directed optimal medical therapy [GDMT] with advanced cardiovascular (e.g., high-dose statin and advanced strategy of antiplatelet regimens) and anti-diabetic medications [e.g., a sodium-glucose cotransporter [SGLT]-2 inhibitors or Glucagon-like peptide-1 [GLP-1] agonists) in patients with type 2 diabetes and three-vessel coronary artery disease (CAD) (not involving left main)
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
The event rate of myocardial infarction		5 years
The event rate of stroke		5 years
Length of hospital stay		7 days
The event rate of rehospitalization	any, cardiac, or noncardiac causes	7 days
The event rate of death from any cause		5 years
The event rate of composite of death from any causes, cardiovascular causes, or noncardiovascular causes		5 years
The event rate of myocardial infarction	any, spontaneous or procedural	5 years
The event rate of composite of death or myocardial infarction		5 years
The event rate of composite of death, myocardial infarction, stroke or repeat revascularization		5 years
The event rate of stent thrombosis	by an Academic Research Consortium (ARC) definition	5 years
The event rate of symptomatic graft occlusion or stenosis		5 years
The event rate of bleeding complications	BARC (Bleeding Academic Research Consortium) criteria	5 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.	5 years
The event rate of repeat revascularization		5 years
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, 36, 60 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, 12, 24, 36, 60 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, 12, 24, 36, 60 months
The number of anti-anginal medications used		1, 6, 12, 18, 24, 36, 60 months
Total healthcare costs and cost-effectiveness assessed using total medical expenditures and incremental cost-effectiveness ratio (ICER)	Total medical cost will be calculated using predefined cost components related to the index revascularization procedure (PCI or CABG) and subsequent healthcare utilization. The list of cost items includes (but is not limited to): diagnostic catheters, guide catheters, guidewires, balloons, stents, adjunctive devices (e.g., rotablation system, intravascular lithotripsy), professional procedure fees, CABG-related graft categories, hospitalization cost per day (Intensive care unit and ward), and non-invasive cardiac tests. Total costs will be aggregated for each participant and compared between study groups at each scheduled time point. Cost-effectiveness will be assessed using the incremental cost-effectiveness ratio (ICER), calculated as the difference in total costs divided by the difference in clinical effectiveness between the study groups.	1, 6, 12, 18, 24, 36, 60 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 (Actual): June 14, 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 (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2025
• Last Verified: December 1, 2025

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: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Coronary Disease; Myocardial Ischemia; Nutritional and Metabolic Diseases; 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