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

NCT05027984 | Recruiting DMC

• 1 other identifier: CLI-01-2020
• Study Type: interventional
• Target: 1,420
• Locations: 4 countries
• Sites: 34

Brief Summary

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.

Conditions

Coronary Artery Disease; Coronary Disease; Ischemic Heart Disease

Keywords

Coronary artery disease; Optical coherence tomography; Vulnerable plaque

Outcome Measures

Primary Outcomes (1)

• Number of patients with cardiac death or non-fatal spontaneous target-vessel myocardial infarction

  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 Outcomes (6)

• Number of patients with cardiac death

  2 years

• Number of patients with non-fatal spontaneous target-vessel Myocardial infarction (excluding peri-procedural MI)

  2 years

• Number of patients with target lesion revascularization (either percutaneous or surgical)

  2 years

• Number of patients with composite of cardiac death and any myocardial infarction

  2 years

• Number of patients with target vessel failure

  2 years

Study Arms (2)

Intermediate lesion OCT-based management

EXPERIMENTAL

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

Intermediate lesion physiology-based management

ACTIVE COMPARATOR

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

Interventions

Optical coherence tomography 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 OCT-based management

iFR/FFR/RFR 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.).

Intermediate lesion physiology-based management

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Centro per la Lotta Contro l'Infarto - Fondazione Onlus: lead
• Abbott Vascular (Santa Clara, USA): collaborator

Study Sites (34)

University Hospital of Patras

Pátrai, AX, 26504, Greece

RECRUITING

Ospedale C. e G. Mazzoni

Ascoli Piceno, AP, 63100, Italy

RECRUITING

Ente ecclesiastico Ospedale Regionale Generale "F. Miulli"

Acquaviva delle Fonti, BA, 70021, Italy

RECRUITING

Policlinico University Hospital

Bari, BA, 70120, Italy

RECRUITING

Di Venere Hospital

Bari, BA, 70131, Italy

RECRUITING

ASST Papa Giovanni XXIII

Bergamo, BG, 24127, Italy

RECRUITING

Azienda Ospedaliera San Pio

Benevento, BN, 82100, Italy

RECRUITING

Azienda Ospedaliero_Universitaria IRCCS Policlinico di St.Orsola

Bologna, BO, 40138, Italy

RECRUITING

ARNAS Brotzu

Cagliari, CA, 09047, Italy

RECRUITING

P.O. San Giuseppe Moscati

Aversa, CE, 81031, Italy

RECRUITING

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

Catania, CT, 95123, Italy

NOT YET RECRUITING

Azienda Ospedaliera Per L'emergenza Cannizzaro

Catania, CT, 95126, Italy

RECRUITING

IRCCS Casa sollievo della sofferenza

San Giovanni Rotondo, FG, 71013, Italy

RECRUITING

IRCCS Ospedale Policlinico San Martino

Genova, GE, 16132, Italy

RECRUITING

Misericordia Hospital

Grosseto, GR, 58100, Italy

RECRUITING

Ospedale Vito Fazzi

Lecce, LE, 73100, Italy

RECRUITING

Ospedale Santa Maria Goretti, Latina

Latina, LT, 04100, Italy

RECRUITING

Azienda Ospedaliero Universitaria Policlinico "G. Martino", Messina

Messina, ME, 98124, Italy

RECRUITING

Centro Cardiologico Monzino IRCCS

Milan, MI, 20138, Italy

RECRUITING

IRCCS Galeazzi- Sant'Ambrogio

Milan, MI, 20157, Italy

RECRUITING

San Camillo Hospital

Roma, RM, 00152, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, RM, 00168, Italy

RECRUITING

UOSA Cardiologia Interventistica

Siena, SI, 53100, Italy

RECRUITING

P.O. Umberto I

Syracuse, SR, 96100, Italy

RECRUITING

Struttura Complessa di Cardiologia Clinica e Interventistica

Sassari, SS, 07100, Italy

NOT YET RECRUITING

Rivoli Hospital

Rivoli, TO, 10098, Italy

RECRUITING

Ospedale Conegliano

Conegliano, TV, 31015, Italy

RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale - Udine University Hospital

Udine, UD, 33100, Italy

RECRUITING

Federico II di Napoli

Napoli, 80138, Italy

RECRUITING

San Giovanni Hospital

Rome, 00184, Italy

RECRUITING

Hospital Virgen de la Victoria

Málaga, MA, 29010, Spain

RECRUITING

Hospital universitario La Princesa, Madrid

Madrid, M, 28006, Spain

RECRUITING

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

RECRUITING

Inselspital, Bern University Hospital

Bern, Canton of Bern, 3010, Switzerland

RECRUITING

Related Publications (12)

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• Toth G, Hamilos M, Pyxaras S, Mangiacapra F, Nelis O, De Vroey F, Di Serafino L, Muller O, Van Mieghem C, Wyffels E, Heyndrickx GR, Bartunek J, Vanderheyden M, Barbato E, Wijns W, De Bruyne B. Evolving concepts of angiogram: fractional flow reserve discordances in 4000 coronary stenoses. Eur Heart J. 2014 Oct 21;35(40):2831-8. doi: 10.1093/eurheartj/ehu094. Epub 2014 Mar 18.

  PMID: 24644308 BACKGROUND

• Pijls NH, van Schaardenburgh P, Manoharan G, Boersma E, Bech JW, van't Veer M, Bar F, Hoorntje J, Koolen J, Wijns W, de Bruyne B. Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study. J Am Coll Cardiol. 2007 May 29;49(21):2105-11. doi: 10.1016/j.jacc.2007.01.087. Epub 2007 May 17.

  PMID: 17531660 BACKGROUND

• Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van' t Veer M, Klauss V, Manoharan G, Engstrom T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med. 2009 Jan 15;360(3):213-24. doi: 10.1056/NEJMoa0807611.

  PMID: 19144937 BACKGROUND

• Burzotta F, Leone AM, Aurigemma C, Zambrano A, Zimbardo G, Arioti M, Vergallo R, De Maria GL, Cerracchio E, Romagnoli E, Trani C, Crea F. Fractional Flow Reserve or Optical Coherence Tomography to Guide Management of Angiographically Intermediate Coronary Stenosis: A Single-Center Trial. JACC Cardiovasc Interv. 2020 Jan 13;13(1):49-58. doi: 10.1016/j.jcin.2019.09.034.

  PMID: 31918942 BACKGROUND

• Waksman R, Legutko J, Singh J, Orlando Q, Marso S, Schloss T, Tugaoen J, DeVries J, Palmer N, Haude M, Swymelar S, Torguson R. FIRST: Fractional Flow Reserve and Intravascular Ultrasound Relationship Study. J Am Coll Cardiol. 2013 Mar 5;61(9):917-23. doi: 10.1016/j.jacc.2012.12.012. Epub 2013 Jan 23.

  PMID: 23352786 BACKGROUND

• Cho YK, Nam CW, Han JK, Koo BK, Doh JH, Ben-Dor I, Waksman R, Pichard A, Murata N, Tanaka N, Lee CH, Gonzalo N, Escaned J, Costa MA, Kubo T, Akasaka T, Hu X, Wang JA, Yang HM, Yoon MH, Tahk SJ, Yoon HJ, Chung IS, Hur SH, Kim KB. Usefulness of combined intravascular ultrasound parameters to predict functional significance of coronary artery stenosis and determinants of mismatch. EuroIntervention. 2015 Jun;11(2):163-70. doi: 10.4244/EIJV11I2A30.

  PMID: 26093837 BACKGROUND

• Usui E, Yonetsu T, Kanaji Y, Hoshino M, Yamaguchi M, Hada M, Hamaya R, Kanno Y, Murai T, Lee T, Kakuta T. Efficacy of Optical Coherence Tomography-derived Morphometric Assessment in Predicting the Physiological Significance of Coronary Stenosis: Head-to-Head Comparison with Intravascular Ultrasound. EuroIntervention. 2018 Apr 6;13(18):e2210-e2218. doi: 10.4244/EIJ-D-17-00613.

  PMID: 29155383 BACKGROUND

• D'Ascenzo F, Barbero U, Cerrato E, Lipinski MJ, Omede P, Montefusco A, Taha S, Naganuma T, Reith S, Voros S, Latib A, Gonzalo N, Quadri G, Colombo A, Biondi-Zoccai G, Escaned J, Moretti C, Gaita F. Accuracy of intravascular ultrasound and optical coherence tomography in identifying functionally significant coronary stenosis according to vessel diameter: A meta-analysis of 2,581 patients and 2,807 lesions. Am Heart J. 2015 May;169(5):663-73. doi: 10.1016/j.ahj.2015.01.013. Epub 2015 Feb 21.

  PMID: 25965714 BACKGROUND

• Prati F, Romagnoli E, Gatto L, La Manna A, Burzotta F, Ozaki Y, Marco V, Boi A, Fineschi M, Fabbiocchi F, Taglieri N, Niccoli G, Trani C, Versaci F, Calligaris G, Ruscica G, Di Giorgio A, Vergallo R, Albertucci M, Biondi-Zoccai G, Tamburino C, Crea F, Alfonso F, Arbustini E. Relationship between coronary plaque morphology of the left anterior descending artery and 12 months clinical outcome: the CLIMA study. Eur Heart J. 2020 Jan 14;41(3):383-391. doi: 10.1093/eurheartj/ehz520.

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• Stone GW, Maehara A, Lansky AJ, de Bruyne B, Cristea E, Mintz GS, Mehran R, McPherson J, Farhat N, Marso SP, Parise H, Templin B, White R, Zhang Z, Serruys PW; PROSPECT Investigators. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011 Jan 20;364(3):226-35. doi: 10.1056/NEJMoa1002358.

  PMID: 21247313 BACKGROUND

• Di Vito L, Agozzino M, Marco V, Ricciardi A, Concardi M, Romagnoli E, Gatto L, Calogero G, Tavazzi L, Arbustini E, Prati F. Identification and quantification of macrophage presence in coronary atherosclerotic plaques by optical coherence tomography. Eur Heart J Cardiovasc Imaging. 2015 Jul;16(7):807-13. doi: 10.1093/ehjci/jeu307. Epub 2015 Jan 14.

  PMID: 25588802 BACKGROUND

MeSH Terms

Conditions

Coronary Artery Disease; Coronary Disease; Myocardial Ischemia

Interventions

Tomography, Optical Coherence

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Tomography, Optical; Optical Imaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Investigative Techniques

Study Officials

• Francesco Prati, MD

  Centro per la Lotta con l'Infarto - CLI Foundation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Francesco Prati, MD

CONTACT

+39 0677055330; fprati61@gmail.com

Flavio Giuseppe Biccirè, MD, PhD

CONTACT

flaviobiccire@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: All events included in the study endpoints will be adjudicated by a blinded Clinical Event Adjudication Committee.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: President of Centro per la Lotta Contro l'Infarto - Fondazione Onlus

Model Details: Two groups: one group receiving functional assessment of intermediate coronary lesions and the other group undergoing OCT assessment.

Study Record Dates

• First Submitted: July 10, 2021
• First Posted: August 31, 2021
• Study Start: June 30, 2021
• Primary Completion: March 31, 2026
• Study Completion (Estimated): March 31, 2028
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After the publication of the main paper
• Access Criteria: Anonymised data will be shared upon reasonable request, after discussion by the Steering Committee.

Locations

CH (1); ES (3); IT (29); GR (1)