Clinical trial NCT03507777: ILUMIEN IV: OPTIMAL Percutaneous Coronary Intervention (PCI)
Official title: OPtical Coherence Tomography (OCT) Guided Coronary Stent IMplantation Compared to Angiography: a Multicenter Randomized TriaL in PCI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Coronary Stenosis
Atherosclerosis
STEMI
STEMI - ST Elevation Myocardial Infarction
NSTEMI - Non-ST Segment Elevation Myocardial Infarction (MI)
Keywords: ABT-CIP-10233
ILUMIEN OPTIS OCT Imaging System
Dragonfly
Optical Coherence Tomography (OCT)
Coronary Stent IMplantation
Angiography
Lead sponsor: Abbott Medical Devices
Sponsor class: INDUSTRY
Collaborators: name: Abbott
First posted: 2018-04-25
Enrollment: 2487
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria (all must be present)

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.

   Note: All lesions in a randomized target vessel that are intended to be treated by PCI are designated as target lesions, and at least one target lesion in each randomized target vessel must meet angiographic high-risk inclusion criteria summarized above in 3B). The only exception is for patients who qualify for the trial on the basis of medication-treated diabetes, in which case no target lesion is required to meet angiographic high-risk inclusion criteria.
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 (none may be present)

Clinical 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.

Angiographic exclusion criteria

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

Primary outcomes:
measure: Imaging Outcome (Powered): Minimal Stent Area (MSA)
timeFrame: Final Post-PCI Measurement (average of 24 hours).
measure: Number of Participants With Target Vessel Failure (TVF)
timeFrame: At 2 years
Secondary outcomes:
measure: Number of Participants With Target Vessel Failure (TVF) Excluding Periprocedural MI (Powered)
timeFrame: At 2 years
measure: The Results of Adjudicated Clinical Outcomes to 2 Years in the Randomized Population
timeFrame: 2 years
measure: The Number of Participants With Stent Thrombosis
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University Hospital - Univ. of Alabama at Birmingham (UAB)
state: Alabama
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Shea
state: Arizona
city: Burlingame
country: United States
facility: Mills-Peninsula Medical Center
state: California
city: Concord
country: United States
facility: John Muir Medical Center
state: California
city: La Jolla
country: United States
facility: Scripps Health
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: University of California - Davis Medical Center
state: California
city: San Diego
country: United States
facility: University of California at San Diego (UCSD) Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Gainesville
country: United States
facility: The Cardiac & Vascular Institute Research Foundation, LLC
state: Florida
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Wichita
country: United States
facility: Via Christi Regional Medical Center - St. Francis Campus
state: Kansas
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute
state: Minnesota
city: Missoula
country: United States
facility: St. Patrick Hospital
state: Montana
city: Bronx
country: United States
facility: Montefiore Medical Center - Moses Division
state: New York
city: Buffalo
country: United States
facility: Buffalo General Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Columbia University
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Asheville
country: United States
facility: Mission Health & Hospitals
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Greenville
country: United States
facility: Eastern Cardiology
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Bend
country: United States
facility: St. Charles Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Health System
state: South Carolina
city: West Columbia
country: United States
facility: Lexington Medical Center
state: South Carolina
city: Nashville
country: United States
facility: Centennial Heart Cardiovascular Consultants
state: Tennessee
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Hospital
state: Texas
city: Ogden
country: United States
facility: McKay-Dee Heart Services
state: Utah
city: Everett
country: United States
facility: Providence Everett Medical Center
state: Washington
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Randwick
country: Australia
facility: Eastern Heart Clinic - Prince of Wales Hospital
city: Aalst
country: Belgium
facility: Onze-Lieve-Vrouwziekenhuis Campus Aalst
state: Eflndrs
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
state: Flemish Brabant
city: Victoria
country: Canada
facility: Royal Jubilee Hospital
state: British Columbia
city: Halifax
country: Canada
facility: QE II Health Sciences
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Science Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Heart Institute
state: Ontario
city: Montreal
country: Canada
facility: CHUM
state: Quebec
city: Montréal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal
state: Quebec
city: Arhus
country: Denmark
facility: Skejby University Hospital
city: Clermont-Ferrand
country: France
facility: CHU Gabriel Montpied
state: Auvergn
city: Besançon
country: France
facility: CHU de Besancon - Jean Minjoz
state: Franche-Comte
city: Lyon
country: France
facility: Hopital Cardiovasculaire et Pneumologique Louis Pradel
state: Rhone-Alpes
city: Erlangen
country: Germany
facility: Kliniken der Friedrich-Alexander-Universitat
state: Bavaria
city: Munich
country: Germany
facility: Deutsches Herzzentrum München des Freistaates Bayern
state: Bavaria
city: Giessen
country: Germany
facility: Klinikum der Justus-Liebig-Universität
state: Hesse
city: Mainz
country: Germany
facility: UNIVERSITATSMEDIZIN der Johannes Gutenberg-Universität Mainz
state: Rhinela
city: Berlin
country: Germany
facility: Universitätsmedizin Berlin - Campus Benjamin Franklin (CBF)
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
state: Hk Sar
city: Hong Kong
country: Hong Kong
facility: Queen Elizabeth Hospital
state: Hk Sar
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
state: Hk Sar
city: Chennai
country: India
facility: Apollo Hospital
state: Tamil Nadu
city: Chennai
country: India
facility: The Madras Medical Mission
state: Tamil Nadu
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education & Research
city: New Delhi
country: India
facility: Max Super Specialty Hospital
city: Roma
country: Italy
facility: Policlinico Universitario A. Gemelli
state: Latium
city: Roma
country: Italy
facility: Az. Osp. S. Giovanni Addolorata
state: Latium
city: Bergamo
country: Italy
facility: Ospedale Papa Giovanni XXIII
state: Lombard
city: Milano
country: Italy
facility: Centro Cardiologico Monzino
state: Lombard
city: Wakayama
country: Japan
facility: Wakayama Medical University
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis
state: South Holland
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
state: Zuid-Holland
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
state: Canterbury
city: Wellington
country: New Zealand
facility: Wellington Hospital
city: Lisboa
country: Portugal
facility: Hospital Santa Marta
state: Lisbon
city: Singapore
country: Singapore
facility: National University Hospital
state: Central
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital - Gothenburg
state: Vastra
city: Bern
country: Switzerland
facility: Center Inselspital Bern
city: Luzern
country: Switzerland
facility: Luzerner Kantonsspital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
state: Ntaiwan
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital (VGH)
state: Ntaiwan
city: Bristol
country: United Kingdom
facility: Bristol Royal Infirmary
state: West Midland
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust
city: London
country: United Kingdom
facility: Kings College Hospital
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Gregg W Stone, MD
role: STUDY_CHAIR
affiliation: Charite University, Berlin, Germany
name: Ulf Landmesser, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St Francis Hospital and Heart Center
name: Ziad A Ali, MD, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.