Multivessel Coronary Artery DiseaseNCT05333068
COMBINE-INTERVENE: COMBINEd Ischemia and Vulnerable Plaque Percutaneous INTERVENtion to Reduce Cardiovascular Events
A study testing PCI revascularization strategy based on combined FFR and OCT assessment and PCI revascularization strategy based FFR assessment in people with Multivessel Coronary Artery Disease and Ischemia, run by Diagram B.V. at 49 sites in 18 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 80 years
- Conditions the study is for
- Multivessel Coronary Artery Disease, Ischemia, Vulnerable Plaque
- What is being tested?
- PCI revascularization strategy based on combined FFR and OCT assessment and PCI revascularization strategy based FFR assessment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,223 participants
- Where
- 49 sitesin 18 countries
- Study dates
- 16 Mar 2022to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing PCI, aged 30-80 years with any clinical presentation
- 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):
- 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.
Who cannot join
- Patients with MVD requiring coronary artery bypass grafting (CABG) treatment (operator / local heart team decision)
- Lesion located in a grafted segment or in a vein graft
- In-stent restenosis lesions
- Left main trifurcation
- Left main lesion stand-alone (without other lesions)
- Patients with severe tortuous lesions (where FFR and OCT is judged impossible or dangerous)
Show all 12Show fewer
- Chronic total occlusion
- Spontaneous coronary dissection
- Patients with severe valvular heart disease likely to require cardiac surgery within the next 2 years
- Patients with left ventricle (LV) function less than 30%
- Renal insufficiency (Glomerular Filtration Rate (GFR) < 29 ml/min/1.73m2; Kidney Disease Outcomes Quality Initiative (KDOQI) stage 4 and 5)
- Life expectancy less than 3 years
Trial locations and contacts
49 sites in 18 countries.
49 sites in 18 countries
Spain9 sites
Hospital Bellvitge Barcelona
Barcelona
Hospital Clínic de Barcelona
Barcelona
Hospital Clinico San Carlos
Madrid
Hospital de La Princesa
Madrid
Hospital Gregorio Marañón Madrid
Madrid
Hospital Universitario Ramon y Cajal
Madrid
University Hospital La Paz
Madrid
Marqués de Valdecilla University Hospital
Santander
Hospital La Fe Valencia
Valencia
Poland6 sites
Medical University of Silesia
Katowice
Jagiellonian University; John Paul II Hospital
Krakow
University Hospital Krakow
Krakow
Miedziowe Centrum Zdrowia
Lubin
Warsaw Medical University
Warsaw
Regional Specialist Hospital
Wroclaw
Netherlands4 sites
OLVG
Amsterdam
Albert Schweitzer Hospital
Dordrecht
Medisch Spectrum Twente
Enschede
Elisabeth-TweeSteden Hospital
Tilburg
Sweden4 sites
Linköping University
Linköping
Lund University
Lund
Universitetssjukhuset Örebro
Örebro
Danderyd Hospital
Stockholm
Canada3 sites
Hamilton Health Sciences
Hamilton
McGill University Health Centre
Montreal
Niagara Health System - St. Catherines Site
Saint Catharines
India3 sites
Apex Heart Institute
Ahmedabad
Apollo Hospitals
Bangalore
Post Graduate Institute of Medical education and Research
Chandigarh
Romania3 sites
C.C. Iliescu Institute of Cardiology Bucharest
Bucharest
Nicolae Stăncioiu Heart Institute
Cluj-Napoca
Clinic Hospital Targu Mures & S.C. Cardio Med SRL
Târgu Mureş
Taiwan3 sites
Far Eastern Memorial Hospital
New Taipei City
Cheng Hsin General Hospital
Taipei
National Taiwan University Hospital
Taipei
France2 sites
Centre Hospitalier Régional Universitaire de Lille
Lille
Clinique Louis Pasteur
Nancy
Germany2 sites
Charité - Universitätsmedizin Berlin
Berlin
Universitätsklinikum Frankfurt
Frankfurt
Italy2 sites
Humanitas Research Hospital
Milan
Policlinico Universitario Fondazione Agostino Gemelli
Rome
Japan2 sites
National University Corporation Institute of Science Tokyo
Bunkyō City
Yokohama City University Medical Center
Yokohama
Slovakia1 site
Middle Slovak Institute of Cardiovascular Disease
Banská Bystrica
About this study
Official title: 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.
Read the 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.
- Being tested
- PCI revascularization strategy based on combined FFR and OCT assessment, PCI revascularization strategy based FFR assessment
- Medical subject headings
- Ischemia, Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PCI revascularization strategy based on combined FFR and OCT assessmentProcedure or surgery
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.
PCI revascularization strategy based FFR assessmentProcedure or surgery
PCI revascularization strategy based FFR assessment (all lesions with FFR≤0.80 will be treated)
| Study group | Role | What they receive |
|---|---|---|
| MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR and OCT assessment | Experimental | MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR and OCT assessment Receives: Procedure: PCI revascularization strategy based on combined FFR and OCT assessment |
| MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR assessment (and sham OCT) | Sham comparator | MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR assessment (and sham OCT) Receives: Procedure: PCI revascularization strategy based FFR assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiac death, any MI or any clinically driven revascularization at 24 months between FFR&OCT guided revascularization versus FFR-guided revascularization
Cardiac death, any MI or any clinically driven revascularization at 24 months between FFR\&OCT guided revascularization versus FFR-guided revascularization
Measured: 24 months
Secondary outcomes (4)
Cardiac death, any MI or any clinical-driven revascularization at 24 months excluding TLR events occurring from medically treated lesions with a FFR between 0.76-0.80 in the experimental arm
Cardiac death, any MI or any clinical-driven revascularization at 24 months excluding TLR events occurring from medically treated lesions with a FFR between 0.76-0.80 in the experimental arm
Measured: 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
Measured: 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
Measured: 24 months
Analysis of corelab-approved primary endpoints, as per protocol analysis
Analysis of corelab-approved primary endpoints, as per protocol analysis
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2022
- Study start16 Mar 2022
- Primary completion16 Sep 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multivessel Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 1,223 participants (actual)
Sponsor and investigators
- Lead sponsor
- Diagram B.V.
- Sponsor type
- University, hospital or other
- Collaborators
- Abbott
- Responsible party
- Sponsor
- Investigators
- Elvin Kedhi, Prof.dr., Principal investigator, Professor of Medicine McGill University; Director Intervention Cardiology, McGill University Health Center, Canada; Visiting Professor, Silesian Medical University Katowice, Poland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05333068
- Sponsor's protocol ID
- 9357
- Status last verified
- Jun 2026
- First submitted
- 11 Apr 2022
- Last updated
- 3 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kedhi E, Wojakowski W, Erlinge D, Akasaka T, Roleder T, Muller J, Malinowski KP, Wlodarczak A, Wlodarczak S, Vijayvergiya R, Patel T, Spaziano M, Akl E, Moreno R, Brugaletta S, Nuruddin AA, Ping Tsao T, Bartus S, Maeng M, Benedek T, Postu M, Van Belle E, Burzotta F, Brown A, Pinilla-Echeverri N, Prati F, De Luca G, Landmesser U, Oemrawsingh RM, Alfonso F. Combined ischaemia and vulnerable plaque percutaneous coronary intervention to reduce cardiovascular events: design and rationale of the COMBINE-INTERVENE Trial. EuroIntervention. 2026 Oct 1:EIJ-D-26-00702. doi: 10.4244/EIJ-D-26-00702. Online ahead of print.
PubMed 42866922
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COMBINEd Ischemia and Vulnerable Plaque Percutaneous INTERVENtion to Reduce Cardiovascular Events
- ClinicalTrials.gov ID
- NCT05333068
- Acronym / sponsor ID
- 9357
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,223 participants (actual)
- Lead sponsor
- Diagram B.V.University, hospital or other
- Collaborators
- Abbott
- Study start
- 16 Mar 2022 (actual)
- Primary completion
- 16 Sep 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 18 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR and OCT assessment | Experimental | Procedure: PCI revascularization strategy based on combined FFR and OCT assessmentMVD > 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) | Sham comparator | Procedure: PCI revascularization strategy based FFR assessmentMVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR assessment (and sham OCT) |
Who may qualify
- Ages
- 30 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients undergoing PCI, aged 30-80 years with any clinical presentation
- 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)
- 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.
Key exclusion criteria (12 listed)
- Patients with MVD requiring coronary artery bypass grafting (CABG) treatment (operator / local heart team decision)
- Lesion located in a grafted segment or in a vein graft
- In-stent restenosis lesions
- Left main trifurcation
- Left main lesion stand-alone (without other lesions)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PCI revascularization strategy based on combined FFR and OCT assessmentPCI 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. | Procedure or surgery | MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR and OCT assessment |
| PCI revascularization strategy based FFR assessmentPCI revascularization strategy based FFR assessment (all lesions with FFR≤0.80 will be treated) | Procedure or surgery | MVD > 2 50% angiographic stenosis PCI revascularization strategy based FFR assessment (and sham OCT) |
Primary outcome
Cardiac death, any MI or any clinically driven revascularization at 24 months between FFR&OCT guided revascularization versus FFR-guided revascularization
Time frame: 24 months
Cardiac death, any MI or any clinically driven revascularization at 24 months between FFR\&OCT guided revascularization versus FFR-guided revascularization
4 secondary outcomes
Cardiac death, any MI or any clinical-driven revascularization at 24 months excluding TLR events occurring from medically treated lesions with a FFR between 0.76-0.80 in the experimental arm
Time frame: 24 months
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
Time frame: 24 months
Analysis of corelab-approved primary endpoints, as per protocol analysis
Time frame: 24 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2026.
- Derived from this study: PubMed 42866922Kedhi E, Wojakowski W, Erlinge D, Akasaka T, Roleder T, Muller J, Malinowski KP, Wlodarczak A, Wlodarczak S, Vijayvergiya R, Patel T, Spaziano M, Akl E, Moreno R, Brugaletta S, Nuruddin AA, Ping Tsao T, Bartus S, Maeng M, Benedek T, Postu M, Van Belle E, Burzotta F, Brown A, Pinilla-Echeverri N, Prati F, De Luca G, Landmesser U, Oemrawsingh RM, Alfonso F. Combined ischaemia and vulnerable plaque percutaneous coronary intervention to reduce cardiovascular events: design and rationale of the COMBINE-INTERVENE Trial. EuroIntervention. 2026 Oct 1:EIJ-D-26-00702. doi: 10.4244/EIJ-D-26-00702. Online ahead of print.
- Diagram B.V.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elvin Kedhi, Prof.dr. principal investigator
Professor of Medicine McGill University; Director Intervention Cardiology, McGill University Health Center, Canada; Visiting Professor, Silesian Medical University Katowice, Poland
49 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PCI revascularization strategy based on combined FFR and OCT assessment and PCI revascularization strategy based FFR assessment in people with Multivessel Coronary Artery Disease and Ischemia, run by Diagram B.V. at 49 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in Spain, Poland, Netherlands, Sweden, Canada and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cardiac death, any MI or any clinically driven revascularization at 24 months between FFR&OCT guided revascularization versus FFR-guided revascularization (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05333068, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.