Interventional Strategy for Non-culprit Lesions With Major Vulnerability Criteria at OCT in Patients With ACS

NCT ID: NCT05027984

Last Updated: 2025-07-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

1420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-30

Study Completion Date

2028-03-31

Brief Summary

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The INTERCLIMA (Interventional Strategy for Non-culprit Lesions With Major Vulnerability Criteria Identified by Optical Coherence Tomography in Patients With Acute Coronary Syndrome) is a multi-center, prospective, randomized trial of optical coherence tomography (OCT)-based versus physiology-based (i.e. fractional flow reserve\[FFR\]/instantaneous Wave-Free Ratio\[iFR\]/resting full-cycle ratio\[RFR\]) treatment of intermediate (40-70% diameter stenosis), non-culprit coronary lesions in acute coronary syndrome (ACS) patients undergoing coronary angiography. About 1420 patients with ACS will be randomized into the study at approximately 40 sites worldwide.

Detailed Description

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The optimal strategy in patients with intermediated stenosis (40-70% diameter stenosis) at coronary angiography is currently under debate. Pure angiographic stenosis evaluation is often inadequate and alternative assessments of coronary plaques entered the clinical practice, such as functional assessment (FFR/iFR/RFR) and intravascular imaging (OCT and intravascular ultrasound \[IVUS\]). Based on preliminary data, current American College of Cardiology (ACC) and American Heart Association (AHA) revascularization guidelines recommend the use of flow fractional reserve (FFR, class IIa of evidence) to assess angiographic intermediate coronary lesions in patients with stable ischemic heart disease and guide intervention. However, controversial data has recently emerged on the role of functional assessment of intermediate coronary lesions in both acute and chronic settings. On the other hand, in recent studies, the presence of coronary plaques with vulnerability criteria at OCT identified patients at high risk of cardiac mortality and target vessel MI. This study aims to assess the clinical effectiveness of an OCT-based strategy to guide revascularization in non-culprit intermediate coronary stenosis in patients with acute coronary syndrome (ACS), on the basis of the presence of morphological markers of plaque vulnerability. Patients with intermediate coronary lesions in non-culprit intervention-naïve major coronary segments (diameter ≥2.5 mm) and fulfilling all inclusion/exclusion criteria will be eligible. Enrolled patients will be randomized 1:1 to either OCT or FFR/RFR/iFR based treatment. In the OCT-guided arm, non-culprit intermediate lesions will be treated with PCI with implantation of a second-generation drug eluting stent (DES) when a FCT \<75 µm plus at least 2 of 3 other OCT criteria of plaque vulnerability (i.e., MLA \<3.5 mm2, lipid arc with circumferential extension \>180°, and the presence of clusters of macrophages) and/or an MLA \<2 mm2 are detected by OCT. In the absence of the above-mentioned 4 vulnerability criteria, interventional procedures will be performed at discretion of the operator if a luminal thrombus is detected by OCT. In the physiology-guided arm, non-culprit intermediate lesions will be treated with PCI with implantation of a second-generation DES when an iFR or RFR ≤0.89 or an FFR ≤0.80 are measured, otherwise interventional procedures will be deferred. The primary endpoint, a composite of cardiac death and target vessel spontaneous myocardial infarction, will be assessed after 2 and 5 years.

Conditions

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Coronary Artery Disease Coronary Disease Ischemic Heart Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Two groups: one group receiving functional assessment of intermediate coronary lesions and the other group undergoing OCT assessment.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
All events included in the study endpoints will be adjudicated by a blinded Clinical Event Adjudication Committee.

Study Groups

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Intermediate lesion OCT-based management

At OCT analysis, lesion features prompting intervention instead of conservative approach will be the following:

1. FCT \<75 µm, plus at least 2 of 3 other OCT criteria of plaque vulnerability (i.e., MLA \<3.5 mm2, lipid arc with circumferential extension \>180°, and the presence of macrophages).
2. The presence of intracoronary thrombus at a non-culprit site, irrespective of the presence of other vulnerability criteria, may prompt treatment with DES, at the operator's discretion.

All lesions fulfilling these interventional criteria will be treated with an OCT guided DES implantation in order to achieve an optimal stent implantation.

In presence of a MLA \<2.0 mm2, best cut-off showing correlation with fractional-flow reserve positive functional (FFR) assessment, clinical decision whether to treat the lesion will be based on FFR assessment irrespective of the presence of other criteria of vulnerability. Alternatively authors will have the option to treat the lesion with a DES.

Group Type EXPERIMENTAL

Optical coherence tomography

Intervention Type DEVICE

OCT images will be acquired by means of the FD C7 XR system or the OPTIS system (both St. Jude Medical, St. Paul, MN, USA) with a non-occlusive technique.(33) The acquired OCT coronary images will be analyzed on-line using a proprietary OCT console (St Jude Medical, Inc., USA). Definitions and cut-offs for OCT vulnerability parameters derived from available consensus documents and from main IVUS/OCT studies.

Intermediate lesion physiology-based management

The iFR/FFR/RFR measurements will be obtained using a coronary-pressure guidewire. For FFR, hyperemia will be induced with the administration of intravenous adenosine, in accordance with the clinical practice at each participating center. Lesion features prompting intervention instead of conservative medical approach will be the following: iFR ≤0.89, or FFR ≤0.80.(32) All lesions fulfilling these interventional criteria will be treated with an FFR guided DES implantation. PCI will be performed with the aim of achieving a post-stenting FFR ≥0.90 (i.e. optimal FFR result). If post-stenting FFR was \<0.90 a further post-dilation of the stent could be performed and if FFR remained at \<0.90, a pullback of the wire to identify another possible pressure drop and/or a subsequent stent implantation at least 5 mm from the stent will be performed according to physician's preference.

Group Type ACTIVE_COMPARATOR

iFR/FFR/RFR

Intervention Type DEVICE

The iFR and FFR measurements will be obtained using a coronary-pressure guidewire (Pressure Wire / Certus or Aeris for FFR assessment and PressureWire™ X Guidewire/QUANTIEM™ for the RFR assessment by Abbott Vascular, Abbott Park, Illinois, U.S.A; Comet by Boston Scientific, Marlborough, MA, USA), OptoWire by Opsens, Quebec, Canada, or Verrata by Philips, San Diego, CA, USA.).

Interventions

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Optical coherence tomography

OCT images will be acquired by means of the FD C7 XR system or the OPTIS system (both St. Jude Medical, St. Paul, MN, USA) with a non-occlusive technique.(33) The acquired OCT coronary images will be analyzed on-line using a proprietary OCT console (St Jude Medical, Inc., USA). Definitions and cut-offs for OCT vulnerability parameters derived from available consensus documents and from main IVUS/OCT studies.

Intervention Type DEVICE

iFR/FFR/RFR

The iFR and FFR measurements will be obtained using a coronary-pressure guidewire (Pressure Wire / Certus or Aeris for FFR assessment and PressureWire™ X Guidewire/QUANTIEM™ for the RFR assessment by Abbott Vascular, Abbott Park, Illinois, U.S.A; Comet by Boston Scientific, Marlborough, MA, USA), OptoWire by Opsens, Quebec, Canada, or Verrata by Philips, San Diego, CA, USA.).

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Age of at least 18 years.
* Diagnosis of acute coronary syndrome.
* Single or multiple intermediate lesions in intervention-naïve major coronary segments (diameter ≥2.5 mm) determining a 40-70% diameter stenosis by visual assessment with no other significant stenosis (\>70%) in the same vessel.
* Patient informed of the nature of the study, agreeing to it, and providing written informed consent as approved by the Ethics Committee of the respective clinical study site.
* Life expectancy \>3 years.

Exclusion Criteria

* Female with childbearing potential or lactating.
* Acute or chronic renal dysfunction (defined as creatinine greater than 2.0 mg/dl).
* Advanced heart failure (NYHA III-IV)
* Stroke within the previous 6 months or spontaneous intracranial hemorrhage at any time.
* Severe valvular disease or valvular disease likely to require surgery or percutaneous valve replacement during the trial.
* Coronary anatomy preventing complete imaging of the segment of interest (including at least 5 mm at both stenosis edges).
* Lesions located in the left main coronary artery
* Diffusely diseased coronary artery segment or presence of ≥1 significant untreated non-culprit lesions (preventing correct adverse event attribution) in the coronary arteries.
* Prior myocardial infarction or coronary artery bypass graft \[CABG\] or PCI revascularization in the target coronary vessel.
* Coronary anatomy unsuitable for PCI.
* Comorbidities that might interfere with completion of the study procedures.
* Planned major surgery necessitating interruption of dual antiplatelet.
* Participating in another investigational drug or device trial that has not completed the primary endpoint or would interfere with the endpoints of this study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Abbott Vascular (Santa Clara, USA)

UNKNOWN

Sponsor Role collaborator

Centro per la Lotta Contro l'Infarto - Fondazione Onlus

OTHER

Sponsor Role lead

Responsible Party

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Francesco Prati

President of Centro per la Lotta Contro l'Infarto - Fondazione Onlus

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Francesco Prati, MD

Role: PRINCIPAL_INVESTIGATOR

Centro per la Lotta con l'Infarto - CLI Foundation

Locations

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University Hospital of Patras

Pátrai, AX, Greece

Site Status RECRUITING

Ospedale C. e G. Mazzoni

Ascoli Piceno, AP, Italy

Site Status RECRUITING

Ente ecclesiastico Ospedale Regionale Generale "F. Miulli"

Acquaviva delle Fonti, BA, Italy

Site Status RECRUITING

Policlinico University Hospital

Bari, BA, Italy

Site Status RECRUITING

Di Venere Hospital

Bari, BA, Italy

Site Status RECRUITING

ASST Papa Giovanni XXIII

Bergamo, BG, Italy

Site Status RECRUITING

Azienda Ospedaliera San Pio

Benevento, BN, Italy

Site Status RECRUITING

Azienda Ospedaliero_Universitaria IRCCS Policlinico di St.Orsola

Bologna, BO, Italy

Site Status RECRUITING

ARNAS Brotzu

Cagliari, CA, Italy

Site Status RECRUITING

P.O. San Giuseppe Moscati

Aversa, CE, Italy

Site Status RECRUITING

Azienda Ospedaliera "Policlinico "G. Rodolico- San Marco"

Catania, CT, Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliera Per L'emergenza Cannizzaro

Catania, CT, Italy

Site Status RECRUITING

IRCCS Casa sollievo della sofferenza

San Giovanni Rotondo, FG, Italy

Site Status RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, GE, Italy

Site Status RECRUITING

Misericordia Hospital

Grosseto, GR, Italy

Site Status RECRUITING

Ospedale Vito Fazzi

Lecce, LE, Italy

Site Status RECRUITING

Ospedale Santa Maria Goretti, Latina

Latina, LT, Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Policlinico "G. Martino", Messina

Messina, ME, Italy

Site Status RECRUITING

Centro Cardiologico Monzino IRCCS

Milan, MI, Italy

Site Status RECRUITING

IRCCS Galeazzi- Sant'Ambrogio

Milan, MI, Italy

Site Status RECRUITING

San Camillo Hospital

Roma, RM, Italy

Site Status RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, RM, Italy

Site Status RECRUITING

UOSA Cardiologia Interventistica

Siena, SI, Italy

Site Status RECRUITING

P.O. Umberto I

Syracuse, SR, Italy

Site Status RECRUITING

Struttura Complessa di Cardiologia Clinica e Interventistica

Sassari, SS, Italy

Site Status NOT_YET_RECRUITING

Rivoli Hospital

Rivoli, TO, Italy

Site Status RECRUITING

Ospedale Conegliano

Conegliano, TV, Italy

Site Status RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale - Udine University Hospital

Udine, UD, Italy

Site Status RECRUITING

Federico II di Napoli

Napoli, , Italy

Site Status RECRUITING

San Giovanni Hospital

Rome, , Italy

Site Status RECRUITING

Hospital Virgen de la Victoria

Málaga, MA, Spain

Site Status RECRUITING

Hospital universitario La Princesa, Madrid

Madrid, M, Spain

Site Status RECRUITING

Hospital Universitario Central de Asturias

Oviedo, , Spain

Site Status RECRUITING

Inselspital, Bern University Hospital

Bern, Canton of Bern, Switzerland

Site Status RECRUITING

Countries

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Greece Italy Spain Switzerland

Central Contacts

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Francesco Prati, MD

Role: CONTACT

+39 0677055330

Flavio Giuseppe Biccirè, MD, PhD

Role: CONTACT

Facility Contacts

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Michail Papafaklis, MD PHD

Role: primary

Luca Di Vito, MD

Role: primary

Elia Iorio, MD

Role: primary

Nicola Signore, MD

Role: primary

Francesco Cassano, MD

Role: primary

Paolo Canova, MD

Role: primary

Marino Scherillo, MD

Role: primary

Nevio Taglieri, MD

Role: primary

Alberto BOI, MD

Role: primary

Gianluca Caiazzo, MD

Role: primary

Piera Capranzano, MD

Role: primary

Francesco Amico, MD

Role: primary

Carlo Vigna, MD

Role: primary

Italo Porto, MD

Role: primary

Andrea Picchi, MD

Role: primary

Dionigi Fischetti, MD

Role: primary

Francesco Versaci, MD

Role: primary

Giampiero Vizzari, MD

Role: primary

Giuseppe Calligaris, MD

Role: primary

Franco Fabbiocchi, MD

Role: primary

Carmine Musto, MD PHD

Role: primary

Enrico Romagnoli, MD

Role: primary

Massimo Fineschi, MD

Role: primary

Marco Contarini, MD

Role: primary

Gavino Casu, MD

Role: primary

Giulio Piedimonte, MD

Role: primary

Gerlando Preti, MD

Role: primary

Enrico Favaretto, MD

Role: primary

Giovanni Esposito, MD

Role: primary

Francesco Prati, MD

Role: primary

Alonso Briales Juan H, MD

Role: primary

Alfonso Fernando, MD PHD

Role: primary

Paula Antuna, MD

Role: primary

Lorenz Räber, MD, PHD

Role: primary

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Provided Documents

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Document Type: Informed Consent Form

View Document

Other Identifiers

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CLI-01-2020

Identifier Type: -

Identifier Source: org_study_id

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