ILUMIEN IV: OPTIMAL PCI

JRCT ID: jRCT1032200080

Registered date:07/08/2020

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Coronary Artery Disease
• Date of first enrollment: 10/11/2020
• Target sample size: 3656
• Countries of recruitment: Australia,Japan,Belgium,Japan,Canada,Japan,Denmark,Japan,France,Japan,Germany,Japan,Hong Kong,Japan,Italy,Japan,Netherland,Japan,New Zealand,Japan,Portugal,Japan,Singapore,Japan,Spain,Japan,Switzerland,Japan,Taiwan,Japan,UK,Japan,USA,Japan
• Study type: Interventional

Intervention(s)

- Coronary PCI guided by OCT (Stent implantation using OCT guidance)
- Coronary PCI guided by Angiography (Stent implantation using OCT guidance)

Outcome(s)

Primary Outcome

- Minimal stent area (MSA) : Post-PCI MSA assessed by OCT in each randomized arm, measured at an independent OCT core laboratory blinded to imaging modality assignment.
- Target vessel failure (TVF): Composite time-to-first event rate of cardiac death, target vessel myocardial infarction (TV-MI), or ischemia-driven target vessel revascularization (ID-TVR)

Secondary Outcome

<Procedural outcomes>
OCT-defined (OCT core laboratory assessed). Subjects in the angiography-guided arm will undergo a post-PCI OCT run, blinded to the operator. Assessed per target lesion.
1)Stent expansion. Stent expansion is defined by the MSA achieved in the proximal and distal stented segments relative to their respective reference lumen areas. The stent length is divided into 2 equal segments (proximal and distal) except for lesions containing a bifurcation (visually estimated side branch >=2.5 mm). When there is a bifurcation present, rather than splitting the stent into two halves, the division occurs at the proximal most side branch.
2)Mean stent expansion (%) (continuous variable): The mean stent area (stent volume/analysed stent length) divided by the average of proximal and distal reference lumen areas x 100.
3)Intra-stent plaque protrusion and thrombus
4)Untreated reference segment disease
5)Edge dissections
6)Stent Malapposition
7)Border detection (angiography arm post-PCI only, blinded to investigator)
8)Intra-stent lumen area (intra-stent flow area)
9)Effective lumen area (total flow area)

<Additional Procedural and Clinical Endpoints>
10)Angiographic Endpoints (QCA). (Angiographic core laboratory assessed). Assessed per target lesion.
11)Device Usage Endpoints (site reported; assessed per subject):
12)Procedure time (first wire insertion to guide catheter removal), fluoroscopy time, radiation exposure
13)Contrast use; contrast induced nephropathy (defined as serum creatinine rise >25% or absolute increase >0.5 mg/dL (44.2micro-mol/L)); need for renal replacement therapy
14)Procedural success (must be present in all treated lesions and vessels)
15)Procedural complications
16)OCT performance success (site reported) (OCT arm only)
17)OCT imaging-related procedural complications (CEC adjudicated)
Any procedural complications (e.g. angiographic dissection, perforation, thrombus, acute closure, etc.) requiring any active intervention (e.g. prolonged balloon inflations, additional stent implantation, pericardiocentesis, intubation, hemodynamic support or pressors, defibrillation or cardioversion) or death adjudicated by the CEC as definitely or likely attributable to the physical performance of OCT-imaging (e.g. passing the catheter through the vasculature or stent, or injecting contrast to clear the blood for imaging). For this definition, adverse events that arise due to changes in PCI strategy as the result of OCT findings are NOT considered OCT imaging-related procedural complications.
18)Additional interventions on the basis of the pre-PCI or post-stent OCT-imaging run that would not have been performed based on angiographic guidance alone (site reported; assessed per subject; OCT Arm Only)

<Clinical outcomes at 30 days, 1 year and 2 years>
19)Target lesion failure (TLF; cardiac death, TV-MI or ischemia-driven target lesion revascularization (ID-TLR)
20)All-cause mortality
21)Cardiac and non-cardiac mortality
22)All myocardial infarction (MI)
23)TV-MI and non-TV-MI
24)Periprocedural MI and non-periprocedural MI
25)All revascularization
26)ID-revascularization and non-ID-revascularization
27)ID-TVR, ID-TLR and ID-non-TLR TVR
28)Definite, probable and definite/probable stent thrombosis (ARC definition)
29)Relationship between immediate post-procedure OCT parameters (e.g. MSA, procedural success, malapposition, dissection, protrusion, etc.) and 2-year endpoint rates (e.g. TVF, TLF, all-cause mortality, cardiac death, TV-MI, all MI, ID-TLR, ID-TVR, and stent thrombosis)

<Patient Reported Outcomes (PRO)>
The following instruments will be administered during this study in hospital (required at baseline, optional post-procedure), and at 30 day, 12 month and 24 month follow-up:
- EuroQoL 5D (EQ-5D-5L) survey to assess overall health status

<Cost-effectiveness>
Cost per quality adjusted life year (QALY) and TVF event prevented by OCT-guidance to be determined using standardized methods.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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),
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.
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.
7. All target lesions intended to be treated by PCI in the target vessel are amenable to OCT-guided PCI (i.e. no lesion-specific angiographic exclusion criteria are present).
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.

Exclude criteria

1. STEMI <=24 hours from the onset of ischemic symptoms
2. Creatinine clearance <=30 ml/min/1.73 m2 (as calculated by MDRD formula for estimated GFR) and not on dialysis.
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
9. Prior PCI within the target vessel within 12 months
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.
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.
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.).
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/mm3 or >700,000 cells/mm3.
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.
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 as evaluated in Section 6.5.1, 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
3. Planned use of a stent or post-dilatation balloon >=3.75 mm for the target lesion (see inclusion criteria #5 for the one exception to this exclusion criterion)
4. Severe vessel tortuosity or calcification in a target vessel such that it is unlikely that the OCT catheter can be delivered
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.
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

Related Information

• Primary Sponsor: Coe Jessie
• Secondary Sponsor: Abbott Laboratories
• Secondary ID(s): NCT03507777