AzTrials
AzTrials

Coronary Artery DiseaseINTERCLIMANCT05027984

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

A study testing Optical coherence tomography and iFR/FFR/RFR in people with Coronary Artery Disease and Coronary Disease, run by Centro per la Lotta Contro l'Infarto - Fondazione Onlus at 34 sites in 4 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Optical coherence tomography and iFR/FFR/RFR
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,425 participants
Where
34 sitesin 4 countries
Study dates
30 Jun 2021to 31 Mar 2030
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
Show all 13Show fewer
  • 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.

Trial locations and contacts

34 sites in 4 countries.

34 sites in 4 countries

Italy29 sites

  • Ente ecclesiastico Ospedale Regionale Generale "F. Miulli"

    Acquaviva delle Fonti, BA, 70021

  • Ospedale C. e G. Mazzoni

    Ascoli Piceno, AP, 63100

  • P.O. San Giuseppe Moscati

    Aversa, CE, 81031

  • Policlinico University Hospital

    Bari, BA, 70120

  • Di Venere Hospital

    Bari, BA, 70131

  • Azienda Ospedaliera San Pio

    Benevento, BN, 82100

  • ASST Papa Giovanni XXIII

    Bergamo, BG, 24127

  • Azienda Ospedaliero_Universitaria IRCCS Policlinico di St.Orsola

    Bologna, BO, 40138

  • ARNAS Brotzu

    Cagliari, CA, 09047

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

    Catania, CT, 95123

  • Azienda Ospedaliera Per L'emergenza Cannizzaro

    Catania, CT, 95126

  • Ospedale Conegliano

    Conegliano, TV, 31015

  • IRCCS Ospedale Policlinico San Martino

    Genova, GE, 16132

  • Misericordia Hospital

    Grosseto, GR, 58100

  • Ospedale Santa Maria Goretti, Latina

    Latina, LT, 04100

  • Ospedale Vito Fazzi

    Lecce, LE, 73100

  • Azienda Ospedaliero Universitaria Policlinico "G. Martino", Messina

    Messina, ME, 98124

  • Centro Cardiologico Monzino IRCCS

    Milan, MI, 20138

  • IRCCS Galeazzi- Sant'Ambrogio

    Milan, MI, 20157

  • Federico II di Napoli

    Naples, 80138

  • Rivoli Hospital

    Rivoli, TO, 10098

  • San Camillo Hospital

    Roma, RM, 00152

  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS

    Roma, RM, 00168

  • San Giovanni Hospital

    Rome, Rome, 00184

  • IRCCS Casa sollievo della sofferenza

    San Giovanni Rotondo, FG, 71013

  • Struttura Complessa di Cardiologia Clinica e Interventistica

    Sassari, SS, 07100

  • UOSA Cardiologia Interventistica

    Siena, SI, 53100

  • P.O. Umberto I

    Syracuse, SR, 96100

  • Azienda Sanitaria Universitaria Friuli Centrale - Udine University Hospital

    Udine, UD, 33100

Other trials in Italy

Spain3 sites

  • Hospital universitario La Princesa, Madrid

    Madrid, M, 28006

  • Hospital Virgen de la Victoria

    Málaga, MA, 29010

  • Hospital Universitario Central de Asturias

    Oviedo, 33011

Other trials in Spain

Greece1 site

  • University Hospital of Patras

    Pátrai, AX, 26504

Other trials in Greece

Switzerland1 site

  • Inselspital, Bern University Hospital

    Bern, Canton of Bern, 3010

Other trials in Switzerland

About this study

Official title: 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.

Read the detailed description

The optimal strategy in patients with intermediate 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 at a median follow-up of 3 years, with extended follow-up through 5 years for all patients for secondary long-term analyses.

Being tested
Optical coherence tomography, iFR/FFR/RFR
Keywords
Coronary artery disease, Optical coherence tomography, Vulnerable plaque
Medical subject headings
Coronary Artery Disease, Coronary Disease, Myocardial Ischemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Optical coherence tomographyDevice

    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.

  • iFR/FFR/RFRDevice

    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.).

Study groups in NCT05027984
Study groupRoleWhat they receive
Intermediate lesion OCT-based managementExperimentalAt 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.
Receives: Device: Optical coherence tomography
Intermediate lesion physiology-based managementActive comparatorThe 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.
Receives: Device: iFR/FFR/RFR

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 3 years

Secondary outcomes (6)

  1. Number of patients with cardiac death

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

    Measured: 3 years

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

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

    Measured: 3 years

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

    Repeated lesion revascularization will be considered in case of repeated percutaneous coronary intervention and coronary artery bypass grafting the enrolled lesions.

    Measured: 3 years

  4. Number of patients with composite of cardiac death and any 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 collected regardless of the culprit vessel involved.

    Measured: 3 years

  5. Number of patients with target vessel failure

    Composite endpoint including cardiac death, non-fatal target-vessel MI, ischemia-driven target lesion revascularization.

    Measured: 3 years

  6. Number of patients with composite endpoint of peri-procedural complications

    • 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.

    Measured: Peri-procedural

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2021
  2. Study start30 Jun 2021
  3. Primary completion31 Jan 2027 (estimated)
  4. Study completion31 Mar 2030 (estimated)

Resources

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
Model description
Two groups: one group receiving functional assessment of intermediate coronary lesions and the other group undergoing OCT assessment.
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
1,425 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05027984
Sponsor's protocol ID
CLI-01-2020
Acronym
INTERCLIMA
Status last verified
Oct 2026
First submitted
10 Jul 2021
Last updated
22 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: After the publication of the main paper, anonymized data will be shared upon reasonable request after discussion by the Steering Committee.

Publications

  • Tonino PA, Fearon WF, De Bruyne B, Oldroyd KG, Leesar MA, Ver Lee PN, Maccarthy PA, Van't Veer M, Pijls NH. Angiographic versus functional severity of coronary artery stenoses in the FAME study fractional flow reserve versus angiography in multivessel evaluation. J Am Coll Cardiol. 2010 Jun 22;55(25):2816-21. doi: 10.1016/j.jacc.2009.11.096.

    PubMed 20579537

  • 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.

    PubMed 24644308

  • 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.

    PubMed 17531660

  • 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.

    PubMed 19144937

  • 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.

    PubMed 31918942

  • 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.

    PubMed 23352786

  • 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.

    PubMed 26093837

  • 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.

    PubMed 29155383

  • 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.

    PubMed 25965714

  • 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.

    PubMed 31504405

  • 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.

    PubMed 21247313

  • 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.

    PubMed 25588802

Questions about this trial

What is this clinical trial studying?

A study testing Optical coherence tomography and iFR/FFR/RFR in people with Coronary Artery Disease and Coronary Disease, run by Centro per la Lotta Contro l'Infarto - Fondazione Onlus at 34 sites in 4 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 13 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 22 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in Italy, Spain, Greece, Switzerland. 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. 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?

Number of patients with cardiac death or non-fatal spontaneous target-vessel myocardial infarction (time frame: 3 years). 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 NCT05027984, which also lists 12 linked publications.

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 22 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in