NCT02989740

Brief Summary

Title: Combined Optical Coherence Tomography Morphologic and Fractional Flow Reserve Hemodynamic Assessment of Non-Culprit Lesions to Better Predict Adverse Event Outcomes in Diabetes Mellitus Patients COMBINE (OCT-FFR) Prospective Register To study the natural evolution of patients with at least one intermediate angiographic but non-hemodynamic significant stenotic lesion, in two subgroups of patients, with TCFA vs. no TCFA as detected by OCT imaging and to compare these two groups of patients with each other as well as to a subset of patients with FFR-positive and PCI-treated intermediate lesions on future MACE.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
550

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started Mar 2015

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 26, 2015

Completed
1.7 years until next milestone

First Submitted

Initial submission to the registry

December 8, 2016

Completed
4 days until next milestone

First Posted

Study publicly available on registry

December 12, 2016

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 30, 2020

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2021

Completed
Last Updated

September 5, 2021

Status Verified

August 1, 2021

Enrollment Period

5.3 years

First QC Date

December 8, 2016

Last Update Submit

August 30, 2021

Conditions

Diabetes MellitusCoronary Artery DiseaseCoronary Atheroscleroses

Keywords

Diabetes MellitusThincap fibroatheromaOptical Coherence TomographyFractional Flow Reserve

Outcome Measures

Primary Outcomes (1)

  • The per patient incidence of the target lesion(s) related composite MACE

    The per patient incidence of the target lesion(s) related composite MACE defined as Cardiac Death, MI, clinically-driven target lesion revascularisation or hospitalization due to unstable or progressive angina at 18 months in the FFR-negative No-TCFA (Group A) and FFR-negative TCFA (Group B).

    18 months after procedure

Secondary Outcomes (3)

  • The per patient incidence of the target lesion(s) related composite MACE:

    18 months after procedure

  • The per patient incidence composite MACE

    18 months after procedure

  • The incidence of MACE (Cardiac death, MI, any clinically driven-revascularization or hospitalization due to unstable or progressive angina)

    18 months after procedure

Study Arms (3)

Group A

Patients with negative FFR (\> 0.80) in the target lesion \& decided on OCT (Optical Coherence Tomography) imaging findings with NO thin-cap fibroatheroma

Procedure: Optical Coherence Tomography

Group B

Patients with negative FFR (\> 0.80) in the target lesion \& decided on OCT (Optical Coherence Tomography) imaging findings presence of ≥ thin-cap fibroatheroma

Procedure: Optical Coherence Tomography

Group C

Patients hosting FFR-positive target lesions that have been treated with PCI as per standard care and have further no TCFA lesions.

Procedure: Optical Coherence Tomography

Interventions

Optical Coherence TomographyPROCEDURE

Patients aged ≥ 18 years bearing target lesions that fulfil the inclusion criteria and have undergone FFR and OCT imaging as per clinical practice will be enrolled in the study.

Also known as: OCT
Group AGroup BGroup C

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

The COMBINE (OCT-FFR) Trial is an investigator driven study: a prospective natural history registry. Patients aged ≥ 18 years bearing target lesions (see definition section) that fulfil the inclusion criteria and have undergone FFR and OCT imaging as per clinical practice will be enrolled in the study.

You may qualify if:

  • Age ≥ 18 years
  • History of DM with any indication for angiography (Stable Angina (SA) or any type of Acute Coronary Syndrome (ACS) including ST-Elevation MI).
  • Coronary angiography, including FFR and OCT imaging of at least one coronary de novo stenosis in a native not-grafted vessel with a visually estimated diameter stenosis (DS) of ≥ 40 - ≤ 80% (target lesion) . Target lesion should be other than the culprit lesion(s) in patients presenting with MI (STEMI or non-STEMI).

You may not qualify if:

  • TIMI flow \< 3 in the target lesion(s)
  • Target lesion reference diameter (on visual estimation) \< 2.0 mm
  • Known left ventricular ejection fraction \<30%
  • Known malignancy
  • Life expectancy \< 2 years
  • Unwilling or unable to provide inform consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Isala

Zwolle, Overijssel, 8025 AB, Netherlands

Location

Related Publications (7)

  • Kennedy MW, Fabris E, Ijsselmuiden AJ, Nef H, Reith S, Escaned J, Alfonso F, van Royen N, Wojakowski W, Witkowski A, Indolfi C, Ottervanger JP, Suryapranata H, Kedhi E. Combined optical coherence tomography morphologic and fractional flow reserve hemodynamic assessment of non- culprit lesions to better predict adverse event outcomes in diabetes mellitus patients: COMBINE (OCT-FFR) prospective study. Rationale and design. Cardiovasc Diabetol. 2016 Oct 10;15(1):144. doi: 10.1186/s12933-016-0464-8.

    PMID: 27724869BACKGROUND

  • Kedhi E, Berta B, Roleder T, Hermanides RS, Fabris E, IJsselmuiden AJJ, Kauer F, Alfonso F, von Birgelen C, Escaned J, Camaro C, Kennedy MW, Pereira B, Magro M, Nef H, Reith S, Al Nooryani A, Rivero F, Malinowski K, De Luca G, Garcia Garcia H, Granada JF, Wojakowski W. Thin-cap fibroatheroma predicts clinical events in diabetic patients with normal fractional flow reserve: the COMBINE OCT-FFR trial. Eur Heart J. 2021 Dec 1;42(45):4671-4679. doi: 10.1093/eurheartj/ehab433.

    PMID: 34345911RESULT

  • Wang Z, Kedhi E, Liu X, Li C, Huang J, Zhong J, Qu X, Wijns W, Tu S; COMBINE OCT-FFR Study Group. Prognostic Implications of Angiographically Derived Coronary Radial Wall Strain in Diabetic Patients and Non-Flow-Limiting Stenosis. JACC Cardiovasc Interv. 2025 May 26;18(10):1232-1242. doi: 10.1016/j.jcin.2025.02.009. Epub 2025 May 10.

    PMID: 40347200DERIVED

  • Volleberg RHJA, Rroku A, Mol JQ, Hermanides RS, van Leeuwen M, Berta B, Meuwissen M, Alfonso F, Wojakowski W, Belkacemi A, Roleder T, Kedhi E, van Royen N; COMBINE (OCT-FFR) and PECTUS-obs investigators. FFR-Negative Nonculprit High-Risk Plaques and Clinical Outcomes in High-Risk Populations: An Individual Patient-Data Pooled Analysis From COMBINE (OCT-FFR) and PECTUS-obs. Circ Cardiovasc Interv. 2025 Feb;18(2):e014667. doi: 10.1161/CIRCINTERVENTIONS.124.014667. Epub 2025 Jan 22.

    PMID: 39840429DERIVED

  • Del Val D, Berta B, Roleder T, Malinowski K, Bastante T, Hermanides RS, Wojakowski W, Fabris E, Cuesta J, De Luca G, Rivero F, Alfonso F, Kedhi E. Vulnerable plaque features and adverse events in patients with diabetes mellitus: a post hoc analysis of the COMBINE OCT-FFR trial. EuroIntervention. 2024 Jun 3;20(11):e707-e717. doi: 10.4244/EIJ-D-23-00628.

    PMID: 38840580DERIVED

  • Fabris E, Berta B, Hommels T, Roleder T, Hermanides RS, Rivero F, von Birgelen C, Escaned J, Camaro C, Kennedy MW, Pereira B, Magro M, Nef H, Reith S, Roleder-Dylewska M, Gasior P, Malinowski KP, De Luca G, Garcia-Garcia HM, Granada JF, Wojakowski W, Kedhi E. Long-term outcomes of patients with normal fractional flow reserve and thin-cap fibroatheroma. EuroIntervention. 2023 Feb 6;18(13):e1099-e1107. doi: 10.4244/EIJ-D-22-00306.

    PMID: 36170036DERIVED

  • Fabris E, Berta B, Roleder T, Hermanides RS, IJsselmuiden AJJ, Kauer F, Alfonso F, von Birgelen C, Escaned J, Camaro C, Kennedy MW, Pereira B, Magro M, Nef H, Reith S, Roleder-Dylewska M, Gasior P, Malinowski K, De Luca G, Garcia-Garcia HM, Granada JF, Wojakowski W, Kedhi E. Thin-Cap Fibroatheroma Rather Than Any Lipid Plaques Increases the Risk of Cardiovascular Events in Diabetic Patients: Insights From the COMBINE OCT-FFR Trial. Circ Cardiovasc Interv. 2022 May;15(5):e011728. doi: 10.1161/CIRCINTERVENTIONS.121.011728. Epub 2022 Apr 29.

    PMID: 35485232DERIVED

Related Links

MeSH Terms

Conditions

Diabetes MellitusCoronary Artery Disease

Interventions

Tomography, Optical Coherence

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesCoronary DiseaseMyocardial IschemiaHeart DiseasesCardiovascular DiseasesArteriosclerosisArterial Occlusive DiseasesVascular Diseases

Intervention Hierarchy (Ancestors)

Tomography, OpticalOptical ImagingDiagnostic ImagingDiagnostic Techniques and ProceduresDiagnosisTomographyInvestigative Techniques

Study Officials

  • E Kedhi, MD PhD

    Erasmus Academical Hospital Brussels

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Target Duration
18 Months
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 8, 2016

First Posted

December 12, 2016

Study Start

March 26, 2015

Primary Completion

June 30, 2020

Study Completion

February 28, 2021

Last Updated

September 5, 2021

Record last verified: 2021-08

Data Sharing

IPD Sharing
Will not share

Locations

NL(1)