Clinical trial NCT05333068: COMBINE-INTERVENE: COMBINEd Ischemia and Vulnerable Plaque Percutaneous INTERVENtion to Reduce Cardiovascular Events
Official title: COMBINEd Ischemia and Vulnerable Plaque Percutaneous INTERVENtion to Reduce Cardiovascular Events
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Multivessel Coronary Artery Disease
Ischemia
Vulnerable Plaque
Coronary Artery Disease
Lead sponsor: Diagram B.V.
Sponsor class: OTHER
Collaborators: name: Abbott
First posted: 2022-04-18
Enrollment: 1222
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: cardiac death, any myocardial infarction (MI) or any clinically-driven revascularization at 24 months
timeFrame: 24 months
Secondary outcomes:
measure: 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
timeFrame: 24 months
measure: Cardiac death, any spontaneous MI or any clinically-driven revascularization at 24 months
timeFrame: 24 months
Other outcomes:
Locations:
city: Clayton
country: Australia
facility: Monash Medical
city: Montreal
country: Canada
facility: McGill University Health Centre
city: Ontario
country: Canada
facility: Hamilton Health Sciences
city: Ontario
country: Canada
facility: Niagara Health System - St. Catherines Site
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Tallinn
country: Estonia
facility: North-Estonia Medical Centre
city: Lille
country: France
facility: Centre Hospitalier Régional Universitaire de Lille
city: Nancy
country: France
facility: Clinique Louis Pasteur
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Ahmedabad
country: India
facility: Apex Heart Institute
city: Bangalore
country: India
facility: Apollo Hospitals
city: Chandigarh
country: India
facility: Post Graduate Institute of Medical education and Research
city: Milan
country: Italy
facility: Humanitas Research Hospital
city: Rome
country: Italy
facility: Policlinico Universitario Fondazione Agostino Gemelli
city: Bunkyo
country: Japan
facility: National University Corporation Institute of Science Tokyo
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
city: Kuala Lumpur
country: Malaysia
facility: National Heart Institute
city: Amsterdam
country: Netherlands
facility: OLVG
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Hospital
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Tilburg
country: Netherlands
facility: Elisabeth-TweeSteden Hospital
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Katowice
country: Poland
facility: Medical University of Silesia
city: Krakow
country: Poland
facility: Jagiellonian University; John Paul II Hospital
city: Krakow
country: Poland
facility: University Hospital Krakow
city: Lubin
country: Poland
facility: Miedziowe Centrum Zdrowia
city: Warsaw
country: Poland
facility: Warsaw Medical University
city: Wroclaw
country: Poland
facility: Regional Specialist Hospital
city: Bucharest
country: Romania
facility: C.C. Iliescu Institute of Cardiology Bucharest
city: Cluj-Napoca
country: Romania
facility: Nicolae Stăncioiu Heart Institute
city: Targu Mures
country: Romania
facility: Clinic Hospital Targu Mures & S.C. Cardio Med SRL
city: Banska Bystrica
country: Slovakia
facility: Middle Slovak Institute of Cardiovascular Disease
city: Barcelona
country: Spain
facility: Hospital Bellvitge Barcelona
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital de La Princesa
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: University Hospital La Paz
city: Santander
country: Spain
facility: Marqués de Valdecilla University Hospital
city: Valencia
country: Spain
facility: Hospital La Fe Valencia
city: Linköping
country: Sweden
facility: Linköping University
city: Lund
country: Sweden
facility: Lund University
city: Stockholm
country: Sweden
facility: Danderyd Hospital
city: Örebro
country: Sweden
facility: Universitetssjukhuset Örebro
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taipei City
country: Taiwan
facility: Cheng Hsin General Hospital
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Professor of Medicine McGill University; Director Intervention Cardiology, McGill University Health Center, Canada; Visiting Professor, Silesian Medical University Katowice, Poland
name: Elvin Kedhi, Prof.dr.
role: PRINCIPAL_INVESTIGATOR
References: