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

COMBINEd Ischemia and Vulnerable Plaque Percutaneous INTERVENtion to Reduce Cardiovascular Events

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.

Study Overview

• Status: Recruiting
• Conditions: Ischemia; Coronary Artery Disease; Multivessel Coronary Artery Disease; Vulnerable Plaque
• Intervention / Treatment: Procedure: PCI revascularization strategy based on combined FFR and OCT assessment; Procedure: PCI revascularization strategy based FFR assessment

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 Type: Interventional
• Enrollment (Anticipated): 1222
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Romania
  • Bucharest, Romania
    • Recruiting
    • Different countries in Europe, Asia Pacific and Canada
    • Contact: PI Different PI's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR and OCT assessment	Procedure: 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.
SHAM_COMPARATOR: MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR assessment (and sham OCT)	Procedure: PCI revascularization strategy based FFR assessment; PCI revascularization strategy based FFR assessment (all lesions with FFR≤0.80 will be treated)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiac death, any myocardial infarction (MI) or any clinically-driven revascularization at 24 months	cardiac death, any myocardial infarction (MI) or any clinically-driven revascularization at 24 months	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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 spontaneous MI or any clinically-driven revascularization at 24 months	Cardiac death, any spontaneous MI or any clinically-driven revascularization at 24 months	24 months

Collaborators and Investigators

• Sponsor: Diagram B.V.
• Collaborators: Abbott
• Investigators: Principal Investigator: Elvin Kedhi, Prof.dr., Director Innovation Clinic, Erasmus Academical Hospital, Université Libre de Bruxelles, Belgium and Silesian Medical University, Poland

Publications and helpful links

Helpful Links

• Diagram B.V.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 16, 2022
• Primary Completion (ANTICIPATED): March 16, 2026
• Study Completion (ANTICIPATED): December 31, 2026

Study Registration Dates

• First Submitted: April 11, 2022
• First Submitted That Met QC Criteria: April 11, 2022
• First Posted (ACTUAL): April 18, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 18, 2022
• Last Update Submitted That Met QC Criteria: April 11, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Ischemia
• Other Study ID Numbers: 9357

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No