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

• ClinicalTrials.gov Identifier: NCT05333068
• Recruitment Status: Recruiting
• First Posted: April 18, 2022
• Last Update Posted: April 18, 2022
• Sponsor: Diagram B.V.
• Collaborator: Abbott
• Information provided by (Responsible Party): Diagram B.V.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multivessel Coronary Artery Disease; Ischemia; Vulnerable Plaque; Coronary Artery Disease	Procedure: PCI revascularization strategy based on combined FFR and OCT assessment; Procedure: PCI revascularization strategy based FFR assessment	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1222 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Masking Description: single blind
• Primary Purpose: Treatment
• Official Title: COMBINEd Ischemia and Vulnerable Plaque Percutaneous INTERVENtion to Reduce Cardiovascular Events
• Actual Study Start Date: March 16, 2022
• Estimated Primary Completion Date: March 16, 2026
• Estimated Study Completion Date: December 31, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: 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	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); 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)

Outcome Measures

Primary Outcome Measures :

1. cardiac death, any myocardial infarction (MI) or any clinically-driven revascularization at 24 months [ Time Frame: 24 months ]
   cardiac death, any myocardial infarction (MI) or any clinically-driven revascularization at 24 months

Secondary Outcome Measures :

1. 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 [ Time Frame: 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
2. Cardiac death, any spontaneous MI or any clinically-driven revascularization at 24 months [ Time Frame: 24 months ]
   Cardiac death, any spontaneous MI or any clinically-driven revascularization at 24 months

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Jolanda Pol-van der Velde, MSc; +31 (0)38 426 2999; jo.pol@diagram-zwolle.nl

Locations

Romania

Different countries in Europe, Asia Pacific and Canada; Recruiting

Bucharest, Romania

Contact: PI Different PI's

Sponsors and Collaborators

Diagram B.V.

Abbott

Investigators

• Principal Investigator: Elvin Kedhi, Prof.dr.; Director Innovation Clinic, Erasmus Academical Hospital, Université Libre de Bruxelles, Belgium and Silesian Medical University, Poland

More Information

Additional Information:

Diagram B.V. 

• Responsible Party: Diagram B.V.
• ClinicalTrials.gov Identifier: NCT05333068
• Other Study ID Numbers: 9357
• First Posted: April 18, 2022
• Last Update Posted: April 18, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes