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

Not Applicable

Active, not recruiting

• Conditions: Coronary Artery Disease; Multivessel Coronary Artery Disease; Ischemia; Vulnerable Plaque
• Interventions: Procedure: PCI revascularization strategy based on combined FFR and OCT assessment; Procedure: PCI revascularization strategy based FFR assessment

• Registration Number: NCT05333068
• Lead Sponsor: Diagram B.V.

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.

Study Timeline

• Study Start: 2022-03-16
• Study First Submitted: 2022-04-11
• Study First Submitted QC: 2022-04-11
• Study First Posted: 2022-04-18
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-31
• Last Update Posted: 2025-02-04
• Primary Completion: 2026-03-16
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1222

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR and OCT assessment	PCI revascularization strategy based on combined FFR and OCT assessment	MVD \> 2 50% angiographic stenosis PCI revascularization strategy based FFR and OCT assessment
MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR assessment (and sham OCT)	PCI revascularization strategy based FFR assessment	MVD \> 2 50% angiographic stenosis PCI revascularization strategy based FFR assessment (and sham OCT)

Primary Outcome Measures

Name	Time	Method
cardiac death, any myocardial infarction (MI) or any clinically-driven revascularization at 24 months	24 months	cardiac death, any myocardial infarction (MI) or any clinically-driven revascularization at 24 months

Secondary Outcome Measures

Name	Time	Method
Cardiac death, any MI or any clinical-driven revascularization at 24 months excluding TLR events in all lesions with a FFR between 0.76-0.80 left untreated in the experimental arm	24 months	Cardiac death, any MI or any clinical-driven revascularization at 24 months excluding TLR events in all lesions with a FFR between 0.76-0.80 left untreated in the experimental arm
Cardiac death, any spontaneous MI or any clinically-driven revascularization at 24 months	24 months	Cardiac death, any spontaneous MI or any clinically-driven revascularization at 24 months

Trial Locations

Locations (49)

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

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; 🇯🇵 Bunkyo, Japan

Middle Slovak Institute of Cardiovascular Disease; 🇸🇰 Banska Bystrica, Slovakia

Hospital Bellvitge Barcelona; 🇪🇸 Barcelona, 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

Danderyd Hospital; 🇸🇪 Stockholm, Sweden

Universitetssjukhuset Örebro; 🇸🇪 Örebro, Sweden

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital de La Princesa; 🇪🇸 Madrid, Spain

Charité - Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt, Germany

Apex Heart Institute; 🇮🇳 Ahmedabad, India

Apollo Hospitals; 🇮🇳 Bangalore, India

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; 🇷🇴 Targu Mures, Romania

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Spain

Far Eastern Memorial Hospital; 🇨🇳 New Taipei City, Taiwan

Cheng Hsin General Hospital; 🇨🇳 Taipei City, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei City, Taiwan