Primary Objective: To prove that in patients with multivessel coronary disease (MVD) (>= 2 lesions with diameter stenosis >=50%) a PCI revascularization strategy based on revascularisation of all lesions presenting a vulnerable plaques…
ID
Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Cardiac death, any MI or any clinically driven revascularization at 24 months
between FFR&OCT guided revascularization versus FFR-guided revascularization
Secondary outcome
Main secondary endpoints
1) Cardiac death, any MI or any clinical-driven revascularization at 24 months
excluding TLR events in patients with FFR between 0.75-0.80 left untreated in
the experimental arm
2) Cardiac death, any spontaneous MI or any clinically driven revascularization
at 24 months
Other secondary endpoints
1) Cardiac death, any MI or any clinically driven revascularization at 24
months between the subgroup of patients with FFR > 0.80 in both arms (to
evaluate the impact of stenting for VP)
2) TLF: Cardiac death, target vessel MI or clinically driven TLR related to
stented lesions at 24 months (impact of OCT guidance in stent outcomes)
3) Outcomes (PE) rate of medically treated patients that have VP free and FFR
value > 0.75 to <= 0.80 lesions versus medically treated patients that have VP
free and FFR > 0.80 lesions (within the FFR & OCT guided arm only, to evaluate
safety of medical treatment for FFR > 0.75 and free of VP)
4) Any death, any MI, any clinically driven revascularization
5) Cardiac Death, any MI or any Clinically Driven Revascularization at 36
months (if funding permits)
6) Cardiac Death, any MI or any Clinically Driven Revascularization at 60
months (if funding permits)
Background summary
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 multivessel
disease with any presentation.
Study objective
Primary Objective:
To prove that in patients with multivessel coronary disease (MVD) (>= 2 lesions
with diameter stenosis >=50%) a PCI revascularization strategy based on
revascularisation of all lesions presenting a vulnerable plaques morphology &
severe ischemic lesions (FFR<= 0.75) is superior to ischemia-guided (fractional
flow reserve (FFR)-guided) only PCI revascularization.
Main secondary objectives
1) Define cut-off of severe ischemia (between 0.75 or 0.80)
2) To compare these two strategies excluding the impact of periprocedural MI
3) Corelab approved per protocol analysis of the primary endpoint
Secondary Objectives:
To compare PCI revascularization strategy based on combined FFR and OCT
assessment with PCI revascularization strategy based on FFR-alone with regard
to the following objectives:
1. Cardiac death, any MI or any clinically driven revascularization at 24
months between the subgroup of patients with FFR > 0.80 in both arms (to
evaluate the impact of stenting for VP)
2. Target lesion failure (TLF): Cardiac death, target vessel MI or clinically
driven target lesion revascularization (TLR) related to stented lesions at 24
months (impact of OCT guidance in stent outcomes)
3. Outcomes (PE rate) of medically treated patients that have VP free and FFR
value > 0.75 to <= 0.80 lesions versus medically treated patients that have VP
free and FFR > 0.80 lesions (within the FFR & OCT guided arm only, to evaluate
safety of medical treatment for FFR > 0.75 and free of VP)
4. Cardiac Death, any MI or any Clinically-Driven Revascularization at 36 and
60 months (if funding permits), to evaluate the outcomes between these two
strategies in long term follow up
*
Study design
The COMBINE-INTERVENE trial is a prospective, randomized, international, sham
controlled, single-blinded superiority trial.
Patients with MVD will be randomized in a 1:1 fashion between FFR & OCT guided
PCI revascularization (experimental arm) and FFR-guided revascularization
(comparative arm).
A follow-up is scheduled at 1 Year and 2 Year.
Intervention
FFR and OCT guided revascularization versus FFR guided (Sham OCT)
revascularization
Study burden and risks
There is no additional risk for patients associated with study participation in
the control arm. It is unlikely that patients will have worse outcomes in the
experimental group. We expect that the use of OCT in the experimental arm will
give a significant reduction on event rate in this arm.
Dokter Stolteweg 96
Zwolle 8025 AZ
NL
Dokter Stolteweg 96
Zwolle 8025 AZ
NL
Listed location countries
Age
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. diameter stenosis >= 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)
*Target lesions are either culprit myocardial infarction 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 multivessel disease 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
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT05333068 |
| CCMO | NL79981.100.21 |