ILUMIEN IV: OPTIMAL Percutaneous Coronary Intervention (PCI)

NCT ID: NCT03507777

Last Updated: 2024-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 2487 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-17
• Study Completion Date: 2023-02-28

Brief Summary

The objective of this prospective, single-blind clinical investigation is to demonstrate the superiority of an Optical Coherence Tomography (OCT)-guided stent implantation strategy as compared to an angiography-guided stent implantation strategy in achieving larger post-PCI lumen dimensions and improving clinical cardiovascular outcomes in patients with high-risk clinical characteristics and/or with high-risk angiographic lesions.

Conditions

Coronary Artery Disease; Coronary Stenosis; Atherosclerosis; STEMI; STEMI - ST Elevation Myocardial Infarction; NSTEMI - Non-ST Segment Elevation Myocardial Infarction (MI)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Coronary PCI guided by OCT

Intervention = Coronary stenting with planned drug eluting stent (DES).

Stenting will be performed with OCT guidance according to the algorithm described in the protocol. OCT imaging is required pre and post stent implantation.

At the end of the procedure, a final OCT imaging run must be performed.

Group Type: ACTIVE_COMPARATOR

Coronary PCI guided by OCT

Intervention Type: DEVICE

Stent implantation in high-risk or complex lesions in patients with coronary artery disease using OCT guidance

Coronary PCI guided by Angiography

Intervention = Coronary stenting with planned drug eluting stent (DES).

Stenting will be performed with angiography guidance according to local standard practice.

At the end of the procedure, a blinded OCT shall be performed to document final stent dimensions and results.

Group Type: ACTIVE_COMPARATOR

Coronary PCI guided by Angiography

Intervention Type: DEVICE

Stent implantation in high-risk or complex lesions in patients with coronary artery disease using angiography guidance

Interventions

Coronary PCI guided by OCT

Stent implantation in high-risk or complex lesions in patients with coronary artery disease using OCT guidance

Intervention Type: DEVICE

Coronary PCI guided by Angiography

Stent implantation in high-risk or complex lesions in patients with coronary artery disease using angiography guidance

Intervention Type: DEVICE

Other Intervention Names

Optical Coherence Tomography

Eligibility Criteria

Inclusion Criteria

1. Subject must be at least 18 years of age.

2. Subject must have evidence of myocardial ischemia (e.g., stable angina, silent ischemia (ischemia in the absence of chest pain or other anginal equivalents), unstable angina, or acute myocardial infarction) suitable for elective PCI.

3. Patients undergoing planned XIENCE stent implantation during a clinically indicated PCI procedure meeting one or more of the following criteria:

A) High clinical-risk, defined as;

i. Medication-treated diabetes mellitus, AND/OR

B) High angiographic-risk lesion(s), with at least one target lesion in each target vessel planned for randomization meeting at least one of the following criteria;

i. Target lesion is the culprit lesion responsible for either:

• NSTEMI, defined as a clinical syndrome consistent with an acute coronary syndrome and a minimum troponin of 1 ng/dL (may or may not have returned to normal), OR
• STEMI >24 hours from the onset of ischemic symptoms

ii. long or multiple lesions (defined as intended total stent length in any single target vessel ≥28 mm),

Note: For a long target lesion, this would permit treatment by a single long stent or overlapping stents.

Note: For up to two target lesions located in a single target vessel and treated with non-overlapping stents, they may be located in a continuous vessel or split up between a main vessel and a side branch.

iii. bifurcation intended to be treated with 2 planned stents (i.e. in both the main branch and side branch), and where the planned side branch stent is ≥ 2.5 mm in diameter by angiographic visual estimation.

iv. angiographic severe calcification (defined as angiographically visible calcification on both sides of the vessel wall in the absence of cardiac motion),

v. chronic total occlusion (CTO) (enrolment and randomization in this case performed only after successful antegrade wire escalation crossing and pre-dilatation)

vi. in-stent restenosis of diffuse or multi-focal pattern. Lesion must be at or within the existing stent margin(s) and have angiographically visually-assessed DS ≥70% or DS ≥50% with non-invasive or invasive evidence of ischemia

4. All target lesions (those lesions to be randomized) must have a visually estimated or quantitatively assessed %DS of either ≥70%, or ≥50% plus one or more of the following: an abnormal functional test (e.g. fractional flow reserve, stress test) signifying ischemia in the distribution of the target lesion(s) or biomarker positive ACS with plaque disruption or thrombus.

Note: For purposes of study eligibility, a minimum troponin of 1 ng/dL at the time of screening will be considered biomarker positive.

5. All target lesions must be planned for treatment with only ≥2.5 mm and ≤3.5 mm stents and post-dilatation balloons based on pre-PCI angiographic visual estimation.

6. No more than 2 target lesions requiring PCI are present in any single vessel., and no more than 2 target vessels are allowed. Thus, up to 4 randomized target lesions per patient in a maximum of 2 target vessels are allowed, including branches. The intended target lesions will be declared just prior to randomization.

Note: A lesion is defined as any segment(s) of the coronary tree, no matter how long, which is planned to be covered with one contiguous length of stent, whether single or overlapped. A bifurcation counts as a single lesion even if the side branch is planned to be treated.

7. All target lesions intended to be treated by PCI in the target vessel are amenable to OCT-guided PCI.

Example: If a qualifying angiographic high-risk lesion is in the proximal LAD, and there is a second target lesion in the distal LAD which is a focal lesion not otherwise meeting high-risk criteria, both the proximal LAD and distal LAD lesions must be amenable to OCT (e.g. no excessive tortuosity or calcification precluding delivering the OCT catheter), and each lesion must undergo OCT-guided stenting. Otherwise the vessel should be excluded from randomization.

8. Subject must provide written Informed Consent prior to any study related procedure.

Exclusion Criteria

1. STEMI ≤24 hours from the onset of ischemic symptoms

2. Creatinine clearance ≤30 ml/min/1.73 m^2 (as calculated by MDRD formula for estimated GFR) and not on dialysis. Note: chronic dialysis dependent patients are eligible for enrolment regardless of creatinine clearance.

3. Hypotension, shock or need for mechanical support or intravenous vasopressors at the time the patient would be undergoing the index procedure.

4. CHF (Killip class ≥2 or NYHA class ≥3)

5. LVEF ≤30% by the most recent imaging test within 3 months prior to procedure. If no LVEF test result within 3 months is available, it must be assessed by echocardiography, multiple gated acquisition (MUGA), magnetic resonance imaging (MRI), ventriculography (LV gram) or other method.

6. Unstable ventricular arrhythmias

7. Inability to take DAPT (both aspirin and a P2Y12 inhibitor) for at least 12 months in the patient presenting with an ACS, or at least 6 months in the patient presenting with stable CAD, unless the patient is also taking chronic oral anticoagulation in which case a shorter duration of DAPT may be prescribed per local standard of care.

8. Planned major cardiac or non-cardiac surgery within 24 months after the index procedure.

Note: Major surgery is any invasive operative procedure in which an extensive resection is performed, e.g. a body cavity is entered, organs are removed, or normal anatomy is altered.

Note: Minor surgery is an operation on the superficial structures of the body or a manipulative procedure that does not involve a serious risk. Planned minor surgery is not excluded.

9. Prior PCI within the target vessel within 12 months

Note: Prior PCI within the target vessel within 12 months is allowed for in-stent restenosis (target lesion is the prior PCI site) if no more than one layer of previously implanted stent is present.

Note: In-stent restenosis involving two or more layers of stent implanted at any time prior to index procedure (i.e. an earlier episode of in-stent restenosis previously treated with a second stent) is excluded.

10. Any planned PCI within the target vessel(s) within 24 months after the study procedure, other than a planned staged intervention in a second randomized target vessel.

Note: Planned staged interventions must be noted at the time of randomization, and the decision to stage may be modified within 24 hours of completion of the index PCI.

Note: PCI in non-target vessels is permitted >48 hours after the index procedure.

11. Any prior PCI in a non-target vessel within 24 hours before the study procedure, or within previous 30 days if unsuccessful or complicated.

Note: Patients requiring non-target vessel PCI may be enrolled and the non-target vessel(s) may be treated in the same index procedure as the randomized lesions (in all cases prior to randomization), as long as treatment of the lesion(s) in the non-target vessel is successful and uncomplicated.

Successful and uncomplicated definition for non-target vessel treatment during the index procedure: Angiographic diameter stenosis <10% for all treated non-target lesions, with TIMI III flow in this vessel, without final dissection ≥ NHLBI type B, perforation anytime during the procedure, prolonged chest pain (>5 minutes) or prolonged ST-segment elevation or depression (>5 minutes), or cardiac arrest or need for defibrillation or cardioversion or hypotension/heart failure requiring mechanical or intravenous hemodynamic support or intubation).

12. Subject has known hypersensitivity or contraindication to any of the study drugs (including all P2Y12 inhibitors, one or more components of the study devices, including everolimus, cobalt, chromium, nickel, platinum, tungsten, acrylic and fluoropolymers, or radiocontrast dye) that cannot be adequately pre-medicated.

13. Subject has received a solid organ transplant which is functioning or is active on a waiting list for any solid organ transplants with expected transplantation within 24 months.

14. Subject is receiving immunosuppressant therapy or has known immunosuppressive or severe autoimmune disease that requires chronic immunosuppressive therapy (e.g., human immunodeficiency virus, systemic lupus erythematosus, etc.). Note: corticosteroids are not included as immunosuppressant therapy.

15. Subject has previously received or is scheduled to receive radiotherapy to a coronary artery (vascular brachytherapy), or the chest/mediastinum.

16. Subject has a platelet count <100,000 cells/mm^3 or >700,000 cells/mm^3.

17. Subject has a documented or suspected hepatic disorder as defined as cirrhosis or Child-Pugh ≥ Class B.

18. Subject has a history of bleeding diathesis or coagulopathy, or has had a significant gastro-intestinal or significant urinary bleed within the past six months.

19. Subject has had a cerebrovascular accident or transient ischemic neurological attack (TIA) within the past six months, or any prior intracranial bleed, or any permanent neurologic defect, or any known intracranial pathology (e.g., aneurysm, arteriovenous malformation, etc.).

20. Subject has extensive peripheral vascular disease that precludes safe 6 French sheath insertion. Note: femoral arterial disease does not exclude the patient if radial access may be used.

21. Subject has life expectancy <2 years for any non-cardiac cause.

22. Subject is currently participating in another investigational drug or device clinical study that has not yet completed its primary endpoint.

23. Pregnant or nursing subjects and those who plan pregnancy in the period up to 2 years following index procedure. Female subjects of child-bearing potential must have a negative pregnancy test done within 7 days prior to the index procedure per site standard test.

24. Presence of other anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements, or impact the scientific soundness of the clinical investigation results.

1. Syntax score ≥33, unless a formal meeting of the Heart Team, including a cardiac surgeon, concludes that PCI is appropriate.

2. Planned use of any stent <2.5 mm in a target vessel based on visual estimation (note: a smaller stent may be used in a bail-out scenario - e.g. to treat a distal dissection - but its use cannot be planned prior to enrolment)

3. Planned use of a stent or post-dilatation balloon ≥3.75 mm for the target lesion

4. Severe vessel tortuosity or calcification in a target vessel such that it is unlikely that the OCT catheter can be delivered (note: severe vessel calcification is allowed if it is expected that the OCT catheter can be delivered at baseline or after vessel preparation with balloon pre-dilatation or atherectomy)

5. The target vessel has a lesion with DS ≥ 50% that is not planned for treatment at the time of index procedure.

6. The target lesion is in the left main coronary artery

7. The target lesion is in a bypass graft conduit. Note: A native coronary artery may be randomized if a prior bypass graft conduit to the vessel is totally occluded, but not if it is patent.

8. The target lesion is an ostial RCA stenosis

9. The target lesion is a stent thrombosis

10. Planned use of any stent other than Xience in a target lesion

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

Abbott Medical Devices

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gregg W Stone, MD

Role: STUDY_CHAIR

Icahn School of Medicine at Mount Sinai

Ulf Landmesser, MD

Role: PRINCIPAL_INVESTIGATOR

Charite University, Berlin, Germany

Ziad A Ali, MD, DPhil

Role: PRINCIPAL_INVESTIGATOR

St Francis Hospital and Heart Center

Locations

University Hospital - Univ. of Alabama at Birmingham (UAB)

Birmingham, Alabama, United States

Scottsdale Healthcare Shea

Scottsdale, Arizona, United States

Mills-Peninsula Medical Center

Burlingame, California, United States

John Muir Medical Center

Concord, California, United States

Scripps Health

La Jolla, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

University of California - Davis Medical Center

Sacramento, California, United States

University of California at San Diego (UCSD) Medical Center

San Diego, California, United States

Stanford University Medical Center

Stanford, California, United States

The Cardiac & Vascular Institute Research Foundation, LLC

Gainesville, Florida, United States

Piedmont Heart Institute

Atlanta, Georgia, United States

Emory University Hospital

Atlanta, Georgia, United States

Loyola University Medical Center

Maywood, Illinois, United States

Kansas University Medical Center

Kansas City, Kansas, United States

Via Christi Regional Medical Center - St. Francis Campus

Wichita, Kansas, United States

Cardiovascular Research Institute of Kansas

Wichita, Kansas, United States

Baptist Health Lexington

Lexington, Kentucky, United States

Brigham & Women's Hospital

Boston, Massachusetts, United States

University of Massachusetts Medical Center

Worcester, Massachusetts, United States

Minneapolis Heart Institute

Minneapolis, Minnesota, United States

St. Patrick Hospital

Missoula, Montana, United States

Buffalo General Hospital

Buffalo, New York, United States

North Shore University Hospital

Manhasset, New York, United States

New York Presbyterian Hospital/Columbia University

New York, New York, United States

St. Francis Hospital

Roslyn, New York, United States

Montefiore Medical Center - Moses Division

The Bronx, New York, United States

Mission Health & Hospitals

Asheville, North Carolina, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Eastern Cardiology

Greenville, North Carolina, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

St. Charles Medical Center

Bend, Oregon, United States

Providence St. Vincent Medical Center

Portland, Oregon, United States

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Greenville Health System

Greenville, South Carolina, United States

Lexington Medical Center

West Columbia, South Carolina, United States

Centennial Heart Cardiovascular Consultants

Nashville, Tennessee, United States

Austin Heart

Austin, Texas, United States

Memorial Hermann Hospital

Houston, Texas, United States

McKay-Dee Heart Services

Ogden, Utah, United States

Providence Everett Medical Center

Everett, Washington, United States

Swedish Medical Center

Seattle, Washington, United States

Fiona Stanley Hospital

Murdoch, Western Australia, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Eastern Heart Clinic - Prince of Wales Hospital

Randwick, , Australia

Onze-Lieve-Vrouwziekenhuis Campus Aalst

Aalst, Eflndrs, Belgium

UZ Gasthuisberg

Leuven, Flemish Brabant, Belgium

Royal Jubilee Hospital

Victoria, British Columbia, Canada

QE II Health Sciences

Halifax, Nova Scotia, Canada

Hamilton Health Science Centre

Hamilton, Ontario, Canada

Ottawa Heart Institute

Ottawa, Ontario, Canada

CHUM

Montreal, Quebec, Canada

Hopital du Sacre-Coeur de Montreal

Montreal, Quebec, Canada

Skejby University Hospital

Aarhus, , Denmark

Hopital Cardiovasculaire et Pneumologique Louis Pradel

Lyon, Auvergne-Rhône-Alpes, France

CHU Gabriel Montpied

Clermont-Ferrand, Auvergn, France

CHU de Besancon - Jean Minjoz

Besançon, Franche-Comte, France

Kliniken der Friedrich-Alexander-Universitat

Erlangen, Bavaria, Germany

Deutsches Herzzentrum München des Freistaates Bayern

Munich, Bavaria, Germany

Klinikum der Justus-Liebig-Universität

Giessen, Hesse, Germany

UNIVERSITATSMEDIZIN der Johannes Gutenberg-Universität Mainz

Mainz, Rhinela, Germany

Universitätsmedizin Berlin - Campus Benjamin Franklin (CBF)

Berlin, , Germany

Prince of Wales Hospital

Hong Kong, HK SAR, Hong Kong

Queen Elizabeth Hospital

Hong Kong, HK SAR, Hong Kong

Queen Mary Hospital

Hong Kong, HK SAR, Hong Kong

Apollo Hospital

Chennai, Tamil Nadu, India

The Madras Medical Mission

Chennai, Tamil Nadu, India

Postgraduate Institute of Medical Education & Research

Chandigarh, , India

Max Super Specialty Hospital

New Delhi, , India

Policlinico Universitario A. Gemelli

Rome, Lazio, Italy

Az. Osp. S. Giovanni Addolorata

Rome, Lazio, Italy

Ospedale Papa Giovanni XXIII

Bergamo, Lombard, Italy

Centro Cardiologico Monzino

Milan, Lombard, Italy

Wakayama Medical University

Wakayama, , Japan

Albert Schweitzer Ziekenhuis

Dordrecht, South Holland, Netherlands

Maasstad Ziekenhuis

Rotterdam, South Holland, Netherlands

Christchurch Hospital

Christchurch, Canterbury, New Zealand

Wellington Hospital

Wellington, , New Zealand

Hospital Santa Marta

Lisbon, Lisbon District, Portugal

National University Hospital

Singapore, Central, Singapore

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Universitario de la Princesa

Madrid, , Spain

Sahlgrenska University Hospital - Gothenburg

Gothenburg, Vastra, Sweden

Center Inselspital Bern

Bern, , Switzerland

Luzerner Kantonsspital

Lucerne, , Switzerland

National Taiwan University Hospital

Taipei, Ntaiwan, Taiwan

Taipei Veterans General Hospital (VGH)

Taipei, Ntaiwan, Taiwan

Bristol Royal Infirmary

Bristol, West Midland, United Kingdom

Papworth Hospital NHS Foundation Trust

Cambridge, , United Kingdom

Kings College Hospital

London, , United Kingdom

Countries

United States; Australia; Belgium; Canada; Denmark; France; Germany; Hong Kong; India; Italy; Japan; Netherlands; New Zealand; Portugal; Singapore; Spain; Sweden; Switzerland; Taiwan; United Kingdom

References

Johnson TW, Bergmark BA, Croce K, Pellegrini D, Maehara A, Gori T, Pinilla-Echeverri N, Wollmuth J, Gonzalo N, Kao HL, Guagliumi G, Phalakornkule K, Ediebah D, McNutt J, Chiu WC, Op den Buijs J, Buccola J, Landmesser U, Ali Z, Stone GW, Jeremias A. Impact of Optical Coherence Tomography-Based Post-PCI Physiology Assessment to Predict Clinical Outcomes: An ILUMIEN-IV Substudy. J Am Coll Cardiol. 2025 Jul 15;86(2):93-102. doi: 10.1016/j.jacc.2025.05.019. Epub 2025 May 22.

Reference Type: DERIVED

PMID: 40406943 (View on PubMed)

Ali ZA, Landmesser U, Maehara A, Shin D, Sakai K, Matsumura M, Shlofmitz RA, Calligaris G, Maksoud A, Abdelwahed YS, Canova P, Gonzalo N, Alfonso F, Fall KN, Chehab B, McGreevy RJ, McNutt RW, Nie H, Wang J, Buccola J, Stone GW; ILUMIEN IV Investigators. Safety and Efficacy of Cobalt Chromium Everolimus-Eluting Stents for Treatment of In-Stent Restenosis: An ILUMIEN IV Substudy. J Am Heart Assoc. 2025 Jun 3;14(11):e039482. doi: 10.1161/JAHA.124.039482. Epub 2025 May 22.

Reference Type: DERIVED

PMID: 40401609 (View on PubMed)

Ali ZA, Landmesser U, Maehara A, Shin D, Sakai K, Matsumura M, Shlofmitz RA, Leistner D, Canova P, Alfonso F, Fabbiocchi F, Guagliumi G, Price MJ, Hill JM, Akasaka T, Prati F, Bezerra HG, Wijns W, McGreevy RJ, McNutt RW, Nie H, Phalakornkule K, Buccola J, Stone GW; ILUMIEN IV Investigators. OCT-Guided vs Angiography-Guided Coronary Stent Implantation in Complex Lesions: An ILUMIEN IV Substudy. J Am Coll Cardiol. 2024 Jul 23;84(4):368-378. doi: 10.1016/j.jacc.2024.04.037. Epub 2024 May 15.

Reference Type: DERIVED

PMID: 38759907 (View on PubMed)

Ali ZA, Landmesser U, Maehara A, Matsumura M, Shlofmitz RA, Guagliumi G, Price MJ, Hill JM, Akasaka T, Prati F, Bezerra HG, Wijns W, Leistner D, Canova P, Alfonso F, Fabbiocchi F, Dogan O, McGreevy RJ, McNutt RW, Nie H, Buccola J, West NEJ, Stone GW; ILUMIEN IV Investigators. Optical Coherence Tomography-Guided versus Angiography-Guided PCI. N Engl J Med. 2023 Oct 19;389(16):1466-1476. doi: 10.1056/NEJMoa2305861. Epub 2023 Aug 27.

Reference Type: DERIVED

PMID: 37634188 (View on PubMed)

Ali Z, Landmesser U, Karimi Galougahi K, Maehara A, Matsumura M, Shlofmitz RA, Guagliumi G, Price MJ, Hill JM, Akasaka T, Prati F, Bezerra HG, Wijns W, Mintz GS, Ben-Yehuda O, McGreevy RJ, Zhang Z, Rapoza RR, West NEJ, Stone GW. Optical coherence tomography-guided coronary stent implantation compared to angiography: a multicentre randomised trial in PCI - design and rationale of ILUMIEN IV: OPTIMAL PCI. EuroIntervention. 2021 Jan 20;16(13):1092-1099. doi: 10.4244/EIJ-D-20-00501.

Reference Type: DERIVED

PMID: 32863246 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SJM-CIP-10218

Identifier Type: OTHER

Identifier Source: secondary_id

ABT-CIP-10233

Identifier Type: -

Identifier Source: org_study_id