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

July 23, 2025 updated by: Francesco Prati, Centro per la Lotta Contro l'Infarto - Fondazione Onlus

An Interventional Strategy for Non-culprit Lesions With Major Vulnerability Criteria Identified by Optical Coherence Tomography in Patients With Acute Coronary Syndrome (the INTER-CLIMA Trial)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

1420

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Greece
    • AX
      • Patras, AX, Greece, 26504
        • Recruiting
        • University Hospital of Patras
        • Contact:
          • Michail Papafaklis, MD PHD
  • Italy
      • Napoli, Italy, 80138
        • Recruiting
        • Federico II di Napoli
        • Contact:
          • Giovanni Esposito, MD
      • Rome, Italy, 00184
        • Recruiting
        • San Giovanni Hospital
        • Contact:
          • Francesco Prati, MD
    • AP
      • Ascoli Piceno, AP, Italy, 63100
        • Recruiting
        • Ospedale C. e G. Mazzoni
        • Contact:
          • Luca Di Vito, MD
    • BA
      • Acquaviva Delle Fonti, BA, Italy, 70021
        • Recruiting
        • Ente ecclesiastico Ospedale Regionale Generale "F. Miulli"
        • Contact:
          • Elia Iorio, MD
      • Bari, BA, Italy, 70120
        • Recruiting
        • Policlinico University Hospital
        • Contact:
          • Nicola Signore, MD
      • Bari, BA, Italy, 70131
        • Recruiting
        • Di Venere Hospital
        • Contact:
          • Francesco Cassano, MD
    • BG
      • Bergamo, BG, Italy, 24127
        • Recruiting
        • Asst Papa Giovanni XXIII
        • Contact:
          • Paolo Canova, MD
    • BN
      • Benevento, BN, Italy, 82100
        • Recruiting
        • Azienda Ospedaliera San Pio
        • Contact:
          • Marino Scherillo, MD
    • BO
      • Bologna, BO, Italy, 40138
        • Recruiting
        • Azienda Ospedaliero_Universitaria IRCCS Policlinico di St.Orsola
        • Contact:
          • Nevio Taglieri, MD
    • CA
      • Cagliari, CA, Italy, 09047
        • Recruiting
        • ARNAS Brotzu
        • Contact:
          • Alberto BOI, MD
    • CE
      • Aversa, CE, Italy, 81031
        • Recruiting
        • P.O. San Giuseppe Moscati
        • Contact:
          • Gianluca Caiazzo, MD
    • CT
      • Catania, CT, Italy, 95123
        • Not yet recruiting
        • Azienda Ospedaliera "Policlinico "G. Rodolico- San Marco"
        • Contact:
          • Piera Capranzano, MD
      • Catania, CT, Italy, 95126
        • Recruiting
        • Azienda Ospedaliera Per L'Emergenza Cannizzaro
        • Contact:
          • Francesco Amico, MD
    • FG
      • San Giovanni Rotondo, FG, Italy, 71013
        • Recruiting
        • IRCCS Casa Sollievo della Sofferenza
        • Contact:
          • Carlo Vigna, MD
    • GE
      • Genova, GE, Italy, 16132
        • Recruiting
        • IRCCS Ospedale Policlinico San Martino
        • Contact:
          • Italo Porto, MD
    • GR
      • Grosseto, GR, Italy, 58100
        • Recruiting
        • Misericordia Hospital
        • Contact:
          • Andrea Picchi, MD
    • LE
      • Lecce, LE, Italy, 73100
        • Recruiting
        • Ospedale Vito Fazzi
        • Contact:
          • Dionigi Fischetti, MD
    • LT
      • Latina, LT, Italy, 04100
        • Recruiting
        • Ospedale Santa Maria Goretti, Latina
        • Contact:
          • Francesco Versaci, MD
    • ME
      • Messina, ME, Italy, 98124
        • Recruiting
        • Azienda Ospedaliero Universitaria Policlinico "G. Martino", Messina
        • Contact:
          • Giampiero Vizzari, MD
    • MI
      • Milano, MI, Italy, 20138
        • Recruiting
        • Centro Cardiologico Monzino IRCCS
        • Contact:
          • Giuseppe Calligaris, MD
      • Milano, MI, Italy, 20157
        • Recruiting
        • IRCCS Galeazzi- Sant'Ambrogio
        • Contact:
          • Franco Fabbiocchi, MD
    • RM
      • Roma, RM, Italy, 00168
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Contact:
          • Enrico Romagnoli, MD
      • Roma, RM, Italy, 00152
        • Recruiting
        • San Camillo Hospital
        • Contact:
          • Carmine Musto, MD PHD
    • SI
      • Siena, SI, Italy, 53100
        • Recruiting
        • UOSA Cardiologia Interventistica
        • Contact:
          • Massimo Fineschi, MD
    • SR
      • Siracusa, SR, Italy, 96100
        • Recruiting
        • P.O. Umberto I
        • Contact:
          • Marco Contarini, MD
    • SS
      • Sassari, SS, Italy, 07100
        • Not yet recruiting
        • Struttura Complessa di Cardiologia Clinica e Interventistica
        • Contact:
          • Gavino Casu, MD
    • TO
      • Rivoli, TO, Italy, 10098
        • Recruiting
        • Rivoli Hospital
        • Contact:
          • Giulio Piedimonte, MD
    • TV
      • Conegliano, TV, Italy, 31015
        • Recruiting
        • Ospedale Conegliano
        • Contact:
          • Gerlando Preti, MD
    • UD
      • Udine, UD, Italy, 33100
        • Recruiting
        • Azienda Sanitaria Universitaria Friuli Centrale - Udine University Hospital
        • Contact:
          • Enrico Favaretto, MD
  • Spain
      • Oviedo, Spain, 33011
        • Recruiting
        • Hospital Universitario Central de Asturias
        • Contact:
          • Paula Antuna, MD
    • M
      • Madrid, M, Spain, 28006
        • Recruiting
        • Hospital universitario La Princesa, Madrid
        • Contact:
          • Alfonso Fernando, MD PHD
    • MA
      • Málaga, MA, Spain, 29010
        • Recruiting
        • Hospital Virgen de la Victoria
        • Contact:
          • Alonso Briales Juan H, MD
  • Switzerland
    • BE
      • Bern, BE, Switzerland, 3010
        • Recruiting
        • Inselspital, Bern University Hospital
        • Contact:
          • Lorenz Räber, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Device: 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.
Active Comparator: 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.
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.).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with cardiac death or non-fatal spontaneous target-vessel myocardial infarction
Time Frame: 2 years

Composite outcome. Cardiac death will be defined as any death due to heart disease, including heart failure, myocardial infarction, arrhythmia, and sudden unexpected death.

Any spontaneous myocardial infarction will be attributed to the randomized intermediate lesion if not clearly attributable to the non-target vessels.
2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with cardiac death
Time Frame: 2 years
Cardiac death will be defined as any death due to heart disease, including heart failure, myocardial infarction, arrhythmia, and sudden unexpected death.
2 years
Number of patients with non-fatal spontaneous target-vessel Myocardial infarction (excluding peri-procedural MI)
Time Frame: 2 years
Any spontaneous myocardial infarction will be attributed to the randomized intermediate lesion if not clearly attributable to the non-target vessels.
2 years
Number of patients with target lesion revascularization (either percutaneous or surgical)
Time Frame: 2 years
Repeated lesion revascularization will be considered in case of repeated percutaneous coronary intervention and coronary artery bypass grafting the enrolled lesions.
2 years
Number of patients with composite of cardiac death and any myocardial infarction
Time Frame: 2 years

Composite outcome. Cardiac death will be defined as any death due to heart disease, including heart failure, myocardial infarction, arrhythmia, and sudden unexpected death.

Any spontaneous myocardial infarction will be collected regardless of the culprit vessel involved.
2 years
Number of patients with target vessel failure
Time Frame: 2 years
Composite endpoint including cardiac death, non-fatal target-vessel MI, ischemia-driven target lesion revascularization.
2 years
Number of patients with composite endpoint of peri-procedural complications
Time Frame: Peri-procedural
  • contrast-induced nephropathy: a 25% increase in serum creatinine (SCr) from baseline or a 0.5 mg/dL (44 µmol/L) increase in absolute SCr value-within 48-72 hours after intravenous contrast administration.
  • dissection requiring bail-out stenting.
  • post-procedural MI: an increase within 48 hours after the index procedure of creatine kinase[CK]-MB (U/L) >5 times or Troponin (ng/L) >35 times above the normal value along with at least one of the followings: 1) symptoms of ischemia; 2) new or presumed new significant ST or T changes or new left bundle branch block; 3) new pathologic Q waves on an electrocardiogram; 4) new loss of viable myocardium or new regional wall motion abnormality; 5) reduced flow or major dissection in the coronary at angiography; or 6) intracoronary thrombus by angiography or autopsy.

A stand-alone biomarker definition will be accepted in case of increase in the cardiac biomarker CK-MB >10 times or Troponin >70 times above the upper normal values.
Peri-procedural

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centro per la Lotta Contro l'Infarto - Fondazione Onlus

Collaborators

Abbott Vascular (Santa Clara, USA)

Investigators

  • Principal Investigator: Francesco Prati, MD, Centro per la Lotta con l'Infarto - CLI Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 30, 2021

Primary Completion (Estimated)

March 31, 2026

Study Completion (Estimated)

March 31, 2028

Study Registration Dates

First Submitted

July 10, 2021

First Submitted That Met QC Criteria

August 24, 2021

First Posted (Actual)

August 31, 2021

Study Record Updates

Last Update Posted (Actual)

July 28, 2025

Last Update Submitted That Met QC Criteria

July 23, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLI-01-2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After the publication of the main paper, anonymized data will be shared upon reasonable request after discussion by the Steering Committee.

IPD Sharing Time Frame

After the publication of the main paper

IPD Sharing Access Criteria

Anonymised data will be shared upon reasonable request, after discussion by the Steering Committee.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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