COMBINE-INTERVENE: COMBINEd Ischemia and Vulnerable Plaque Percutaneous INTERVENtion to Reduce Cardiovascular Events

NCT ID: NCT05333068

Last Updated: 2025-02-04

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 1222 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-16
• Study Completion Date: 2026-12-31

Brief Summary

The COMBINE-INTERVENE Trial will investigate whether a PCI revascularization strategy based on combined FFR and OCT assessment is superior to a PCI revascularization strategy based on FFR-alone in patients with MVD with any presentation.

Detailed Description

The published COMBINE trial shows that patients carrying an OCT-detected thin-cap atheroma have a fivefold higher rate of the primary endpoint compared to patients without vulnerable lesion morphology, despite absence of ischemia. The most important finding of this trial is that not ischemia, but underlying lesion morphology could be the most important factor that predicts future adverse events. Together with the recently published ISCHEMIA trial, where ischemia guided revascularization failed to improve clinical outcomes compared to medical treatment, the COMBINE trial leads to a new way of thinking in interventional cardiology and also opens the door for new treatment strategies where a combined ischemic and morphologic assessment could lead to better clinical outcomes.

The COMBINE-INTERVENE Trial will investigate whether a PCI revascularization strategy based on combined FFR and OCT assessment is superior to a PCI revascularization strategy based on FFR-alone in patients with MVD with any presentation. The COMBINE-INTERVENE Trial is the first in line trial that will test focal percutaneous stenting for vulnerable plaque lesions independently from ischemia.

Conditions

Multivessel Coronary Artery Disease; Ischemia; Vulnerable Plaque; Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR and OCT assessment

MVD \> 2 50% angiographic stenosis PCI revascularization strategy based FFR and OCT assessment

Group Type: EXPERIMENTAL

PCI revascularization strategy based on combined FFR and OCT assessment

Intervention Type: PROCEDURE

PCI revascularization strategy based on combined FFR and OCT assessment All FFR ≤ 0.75 and Vulnerable plaque will be treated. VP defined as TCFA ( cap thickness ≤ 75 micron); Ruptured plaque; or Plaque erosion with \> 70 % AS or MLA \< 2.5 mm2.

MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR assessment (and sham OCT)

MVD \> 2 50% angiographic stenosis PCI revascularization strategy based FFR assessment (and sham OCT)

Group Type: SHAM_COMPARATOR

PCI revascularization strategy based FFR assessment

Intervention Type: PROCEDURE

PCI revascularization strategy based FFR assessment (all lesions with FFR≤0.80 will be treated)

Interventions

PCI revascularization strategy based on combined FFR and OCT assessment

PCI revascularization strategy based on combined FFR and OCT assessment All FFR ≤ 0.75 and Vulnerable plaque will be treated. VP defined as TCFA ( cap thickness ≤ 75 micron); Ruptured plaque; or Plaque erosion with \> 70 % AS or MLA \< 2.5 mm2.

Intervention Type: PROCEDURE

PCI revascularization strategy based FFR assessment

PCI revascularization strategy based FFR assessment (all lesions with FFR≤0.80 will be treated)

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Patients undergoing PCI, aged 30-80 years with any clinical presentation

2. Angiographic criteria: presence of ≥ 2 de novo target lesions* located in 2 different native coronary arteries feasible for treatment with PCI (operator / Heart team decision)

Angiographic criteria target lesion* (all criteria I-IV should be applicable):

I. DS ≥ 50% on visual estimation II. de novo lesion located in native (non-grafted) vessel III. lesion reference diameter of ≥ 2.0 mm IV. Thrombolysis In Myocardial Infarction (TIMI) 3 flow in all vessels (with exclusion of culprit lesions if MI at presentation)

*Target lesions are either culprit MI lesions or lesions where FFR will be performed. Patients are eligible if they have ≥ 2 target lesions or one culprit and ≥ 1 target lesion.

Exclusion Criteria

1. Patients with MVD requiring coronary artery bypass grafting (CABG) treatment (operator / local heart team decision)

2. Lesion located in a grafted segment or in a vein graft

3. In-stent restenosis lesions

4. Left main trifurcation

5. Left main lesion stand-alone (without other lesions)

6. Patients with severe tortuous lesions (where FFR and OCT is judged impossible or dangerous)

7. Chronic total occlusion

8. Spontaneous coronary dissection

9. Patients with severe valvular heart disease likely to require cardiac surgery within the next 2 years

10. Patients with left ventricle (LV) function less than 30%

11. Renal insufficiency (Glomerular Filtration Rate (GFR) < 29 ml/min/1.73m2; Kidney Disease Outcomes Quality Initiative (KDOQI) stage 4 and 5)

12. Life expectancy less than 3 years

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

Diagram B.V.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elvin Kedhi, Prof.dr.

Role: PRINCIPAL_INVESTIGATOR

Professor of Medicine McGill University; Director Intervention Cardiology, McGill University Health Center, Canada; Visiting Professor, Silesian Medical University Katowice, Poland

Locations

Monash Medical

Clayton, , Australia

McGill University Health Centre

Montreal, , Canada

Hamilton Health Sciences

Ontario, , Canada

Niagara Health System - St. Catherines Site

Ontario, , Canada

Aarhus University Hospital

Aarhus, , Denmark

North-Estonia Medical Centre

Tallinn, , Estonia

Centre Hospitalier Régional Universitaire de Lille

Lille, , France

Clinique Louis Pasteur

Nancy, , France

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Universitätsklinikum Frankfurt

Frankfurt, , Germany

Apex Heart Institute

Ahmedabad, , India

Apollo Hospitals

Bangalore, , India

Post Graduate Institute of Medical education and Research

Chandigarh, , India

Humanitas Research Hospital

Milan, , Italy

Policlinico Universitario Fondazione Agostino Gemelli

Rome, , Italy

National University Corporation Institute of Science Tokyo

Bunkyō City, , Japan

Yokohama City University Medical Center

Yokohama, , Japan

National Heart Institute

Kuala Lumpur, , Malaysia

OLVG

Amsterdam, , Netherlands

Albert Schweitzer Hospital

Dordrecht, , Netherlands

Medisch Spectrum Twente

Enschede, , Netherlands

Elisabeth-TweeSteden Hospital

Tilburg, , Netherlands

Wellington Hospital

Wellington, , New Zealand

Medical University of Silesia

Katowice, , Poland

Jagiellonian University; John Paul II Hospital

Krakow, , Poland

University Hospital Krakow

Krakow, , Poland

Miedziowe Centrum Zdrowia

Lubin, , Poland

Warsaw Medical University

Warsaw, , Poland

Regional Specialist Hospital

Wroclaw, , Poland

C.C. Iliescu Institute of Cardiology Bucharest

Bucharest, , Romania

Nicolae Stăncioiu Heart Institute

Cluj-Napoca, , Romania

Clinic Hospital Targu Mures & S.C. Cardio Med SRL

Târgu Mureş, , Romania

Middle Slovak Institute of Cardiovascular Disease

Banská Bystrica, , Slovakia

Hospital Bellvitge Barcelona

Barcelona, , Spain

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital Clinico San Carlos

Madrid, , Spain

Hospital de La Princesa

Madrid, , Spain

Hospital Gregorio Marañón Madrid

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

University Hospital La Paz

Madrid, , Spain

Marqués de Valdecilla University Hospital

Santander, , Spain

Hospital La Fe Valencia

Valencia, , Spain

Linköping University

Linköping, , Sweden

Lund University

Lund, , Sweden

Universitetssjukhuset Örebro

Örebro, , Sweden

Danderyd Hospital

Stockholm, , Sweden

Far Eastern Memorial Hospital

New Taipei City, , Taiwan

Cheng Hsin General Hospital

Taipei, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Countries

Australia; Canada; Denmark; Estonia; France; Germany; India; Italy; Japan; Malaysia; Netherlands; New Zealand; Poland; Romania; Slovakia; Spain; Sweden; Taiwan

Related Links

https://diagramresearch.com/trials/

Diagram B.V.

Other Identifiers

9357

Identifier Type: -

Identifier Source: org_study_id