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

Official title

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)

Overview

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).

Interventions

• 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 an
• Procedure standard CABG
  Coronary-Artery Bypass Grafting

Primary outcome measures

• The event rate of major adverse cardiac or cerebrovascular events [Time frame: 2 years]

Secondary outcome measures (12)

• The event rate of death from any cause [Time frame: 5 years]
• The event rate of myocardial infarction [Time frame: 5 years]
• The event rate of repeat revascularization [Time frame: 5 years]
• The event rate of stroke [Time frame: 5 years]
• The event rate of composite of death from any causes, cardiovascular causes, or noncardiovascular causes [Time frame: 5 years]
• The event rate of myocardial infarction [Time frame: 5 years]
• The event rate of composite of death or myocardial infarction [Time frame: 5 years]
• The event rate of composite of death, myocardial infarction, stroke or repeat revascularization [Time frame: 5 years]
• The event rate of stent thrombosis [Time frame: 5 years]
• The event rate of symptomatic graft occlusion or stenosis [Time frame: 5 years]
• The event rate of bleeding complications [Time frame: 5 years]
• The event rate of periprocedural major adverse events [Time frame: 5 years]

Eligibility criteria

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% \[48 mmol/mol\]).
• 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.
• 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.
• 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 prasugrel) 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. 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

South Korea · 21 centers

• Bucheon Sejong Hospital — Bucheon-si
• Daegu Catholic University Medical Center — Daegu
• Keimyung University Dongsan Medical Center — Daegu
• Yeungnam University Medical Center — Daegu
• Chungnam National University Hospital — Daejeon
• Konyang University Hospital — Daejeon
• Gangneung Asan Hospital — Gangneung
• Chonnam National University Hospital — Gwangju
• … and 13 more centers

India · 3 centers

• Mody Harvard Cardiac Institute — Bathinda
• Medanta - The Medicity — Gurugram
• Fortis Escorts Heart Institute — New Delhi

Thailand · 3 centers

• Siriraj Hospital — Bangkok
• Siriraj Hospital — Bangkok
• Srinagarind Hospital — Khon Kaen

China · 2 centers

• Fuwai Hospital, Chinese Academy of Medical Sciences (CAMS) — Beijing
• Second Affiliated Hospital of Zhejiang University School of Medicine — Hanzhou

United States · 1 center

• Palo Alto VA Medical Center — Palo Alto

Australia · 1 center

• Victorian Heart Institute — Clayton

Hong Kong · 1 center

• Queen Mary Hospital — Hong Kong

Japan · 1 center

• Tsuchiura Kyodo Hospital — Tsuchiura

Latvia · 1 center

• Pauls Stradins Clinical University Hospital — Riga

Lithuania · 1 center

• Vilnius University Hospital Santaros Klinikos — Vilnius

Malaysia · 1 center

• Sarawak Heart Centre — Kota Samarahan

Serbia · 1 center

• University Clinical Center of Serbia — Belgrade

Singapore · 1 center

• National Heart Centre Singapore (NHCS) — Singapore

Taiwan · 1 center

• National Taiwan University Hospital — Taipei

Identifiers

NCT: NCT05831085 · AMCCV2023-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗