OPTIMIZE PCI: Multicenter Randomized Trial of OCT Compared to IVUS and Angiography to Guide Coronary Stent Implantation

Study Overview
=================
Brief Summary
-----------------
The objective of this clinical investigation is to demonstrate the safety and efficacy of an OCT guided strategy for stent implantation

Detailed Description
-----------------
This is a prospective, post-market, international, multi-center, randomized clinical investigation in which the participants will be randomized in 1:1:1 ratio to undergo PCI with either OCT, IVUS, or Angiography guidance. The clinical investigation will be conducted at approximately 35 sites in the United States and outside the United States; approximately 25% of subjects will be enrolled in the United States. Patients in the IVUS and OCT groups patients will undergo baseline and post PCI imaging with their randomized modality. In addition, the Angiography group and IVUS groups will undergo a blinded post-PCI OCT run to allow comparison of OCT derived minimum stent area (MSA) in both groups. After hospital discharge, all patients will have clinical follow-up at 30 days, and 1 year.

Official Title
-----------------
ILUMIEN III: OPTIMIZE PCI: OPtical Coherence Tomography (OCT) Compared to Intravascular Ultrasound (IVUS) and Angiography to Guide Coronary Stent Implantation: a Multicenter RandomIZEd Trial in Percutaneous Coronary Intervention (PCI)

Conditions
-----------------
Coronary Artery Disease

Intervention / Treatment
-----------------
* Procedure: Coronary PCI guided by IVUS
* Procedure: Coronary PCI guided by OCT
* Procedure: Coronary PCI guided by Angiography


Participation Criteria
=================
Eligibility Criteria
-----------------
General Inclusion Criteria: Age ≥ 18 years. Patient with an indication for PCI including: Angina (stable or unstable), Silent ischemia (a visually estimated target lesion diameter stenosis of ≥70%, a positive non-invasive stress test, or FFR ≤0.80 must be present), NSTEMI, or Recent STEMI (>24 hours from initial presentation and stable). Patients will undergo cardiac catheterization and possible or definite PCI with intent to stent using any non-investigational metallic drug-eluting stent (DES) Signed written informed consent Angiographic inclusion criteria: The target lesion must be located in a native coronary artery with visually estimated reference vessel diameter of ≥2.25 mm to ≤3.50 mm. Lesion length <40mm General Exclusion Criteria: Estimated creatinine clearance <30 ml/min using Cockcroft-Gault equation, unless the patient is on dialysis STEMI within 24 hours of initial time of presentation to the first treating hospital, whether at a transfer facility or the study hospital. PCI within 24 hours preceding the study procedure. PCI of a lesion within the target vessel within 12 months prior to the study procedure Planned use of bare metal stent (BMS) Planned use of bioresorbable vascular scaffold (BVS) Cardiogenic shock (defined as persistent hypotension (systolic blood pressure <90 mm/Hg for more than 30 minutes) or requiring pressors or hemodynamic support, including IABP, at time of procedure. Mobitz II second degree or complete heart block Malignant ventricular arrhythmias requiring treatment Pulmonary edema defined as patient with shortness of breath, evidence of volume overload on physical exam, and crepitations on physical exam (>1/3 of lungs) or radiographic interstitial or alveolar pulmonary edema Subject is intubated. Known LVEF <30%. Severe valvular disease (e.g. severe mitral regurgitation or severe aortic stenosis) Cerebrovascular accident or transient ischemic attack within the past 6 months, or any permanent neurologic defect attributed to CVA. Presence of one or more co-morbidities which reduces life expectancy to less than 12 months or may interfere with protocol study processes. Known allergy to protocol-required concomitant medications including aspirin; clopidogrel, prasugrel, and ticagrelor; heparin and bivalirudin; or iodinated contrast that cannot be adequately pre-medicated. Patient is participating in any other investigational drug or device clinical trial that has not reached its primary endpoint. Women who are pregnant or breastfeeding (women of child-bearing potential must have a negative pregnancy test within one week before treatment). Angiographic Exclusion Criteria: The presence of any non-study lesion in the target vessel with angiographic diameter stenosis >50%, or any additional target vessel stenosis which requires PCI either during or within 12 months after the study procedure Left main diameter stenosis ≥30% or left main PCI planned. Study target lesion in a bypass graft Ostial RCA study target lesion Chronic total occlusion (TIMI flow 0/1) study target lesion Bifurcation study lesion with a planned dual stent strategy In-stent restenosis study target lesion Any study lesion characteristic resulting in the expected inability to deliver the IVUS or OCT catheter to the lesion pre and post PCI (e.g. moderate or severe vessel calcification or tortuosity)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Coronary PCI guided by IVUS<br>Intervention = Coronary stenting with planned drug eluting stent (DES). Stenting will be performed with IVUS guidance according to local standard practice. IVUS imaging is required pre and post stent implantation. At the end of the procedure, a final IVUS imaging run must be performed. After the final IVUS run, a blinded OCT imaging run shall be performed to document final stent dimensions and results. | Procedure: Coronary PCI guided by IVUS<br>* Imaging type<br>* Other names: Intravascular Ultrasound;|
| Active Comparator: Coronary PCI guided by OCT<br>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. | Procedure: Coronary PCI guided by OCT<br>* Imaging type<br>* Other names: Optical Coherence Tomography;|
| Active Comparator: Coronary PCI guided by Angiography<br>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. | Procedure: Coronary PCI guided by Angiography<br>* Imaging type<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Endpoint (Powered): Post-PCI Median Minimum Stent Area (MSA) | Post-PCI MSA will be assessed by OCT in each randomized arm, measured at the independent OCT core laboratory blinded to imaging modality assignment. Hierarchal manner testing will be as follows: Non-inferiority: OCT vs. IVUS guided stenting Non-inferiority of OCT guided stenting to IVUS guided stenting will be analyzed for the mean difference between the post PCI MSA for the OCT and IVUS arms with non-inferiority margin of 1.0 mm^2. Superiority: OCT vs. Angiography guided stenting If the OCT guided stenting arm was found to be non-inferior to the IVUS guided stenting arm, the superiority of OCT to angiography will be tested for the mean difference between the post PCI MSA for the OCT and angiography arms. Superiority: OCT vs. IVUS guided stenting If the OCT guided stenting arm was found to be superior to the IVUS guided stenting arm, then the superiority of OCT to IVUS will be tested for the mean difference between the post PCI MSA for the OCT and IVUS arms. | Post-procedure within 1 hour | 
| Primary Safety Endpoint (Non-powered): Number of Participants With Procedural MACE (Major Adverse Cardiac Event) | Procedural MACE defined as procedural complications (angiographic dissection, perforation, thrombus, and acute closure) requiring active interventions (prolonged balloon inflations, additional stent implantations, pericardiocentesis, thrombus aspiration and other). | During procedure, an average of 1 hour | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Acute Procedural Success | Acute procedural success are classified as: A) Optimal (%) The MSA of the proximal segment is ≥95% of the proximal reference lumen area and the MSA of the distal segment is ≥95% of the distal reference lumen area. B) Acceptable (%) The MSA of the proximal segment is ≥90% and <95% of the proximal reference lumen area and the MSA of the distal segment is ≥90% and <95% of the distal reference lumen area. C) Optimal and Acceptable (%) The MSA of the proximal segment is ≥90% and <95% of the proximal reference lumen area and the MSA of the distal segment is ≥90% and <95% of the distal reference lumen area. D) Unacceptable (%) The MSA of the proximal segment is <90% of the proximal lumen area, and/or the MSA of the distal segment is <90% of the distal reference lumen area. | During procedure, an average of 1 hour | 
| Rate of Post-PCI Stent Expansion (%) | Post-PCI stent expansion is defined as the minimum stent area divided by the average of proximal and distal reference lumen areas x 100. | Up to 1 hour post-procedure | 
| Rate of Mean Stent Expansion (%) | Mean stent expansion is defined as the mean stent area (stent volume/analyzed stent length) divided by the average of proximal and distal reference lumen areas x 100. | During procedure, an average of 1 hour | 
| Number of Participants With Plaque Protrusion and Thrombus | Plaque protrusion and thrombus is defined as a mass attached to the luminal surface or floating within the lumen, meeting the following criteria: Protrusion is defined as any mass at least 0.2 mm beyond the luminal edge of a strut and will be further classified as Major and Minor. Major: Protrusion area/Stent area at site of tissue protrusion ≥10% Minor: Protrusion area/Stent area at site of tissue protrusion<10% | During procedure, an average of 1 hour | 
| Number of Participants With Untreated Reference Segment Disease | Untreated reference segment disease is defined as untreated Mean Lumen Area (MLA) ≤60% of the adjacent reference segment lumen area up to 10 mm from the proximal and distal stent edges. | During procedure, an average of 1 hour | 
| Number of Participants With Edge Dissections | Edge Dissections are classified as A) Major (%): ≥60 degrees of the circumference of the vessel at site of dissection and/or ≥3 mm in length B) Minor (%): any visible edge dissection <60 degrees of the circumference of the vessel and < 3 mm in length C) All (Major and Minor) Edge dissections will be further classified as: I. Intimal (limited to the intima layer, i.e. not extending beyond the internal elastic lamina) II. Medial (extending into the media layer) III. Adventitial (extending through the external elastic membrane | During procedure, an average of 1 hour | 
| Number of Participants With Stent Malapposition | Frequency (%) of incompletely apposed stent struts (defined as stent struts clearly separated from the vessel wall (lumen border/plaque surface) without any tissue behind the struts with a distance from the adjacent intima of ≥0.2 mm and not associated with any side branch). Malapposition will be further classified as: Major: if associated with unacceptable stent expansion Minor: if not associated with significant under-expansion | During procedure, an average of 1 hour | 
| Number of Participants With Border Detection (OCT Arm Only) | The visibility of the vessel external elastic lamina (EEL) border by OCT will be evaluated at both reference sites (proximal and distal) and the MSA before AND after intervention and then classified into 3 grades: A) Good: ≥75% (270°) of visible circumference B) Moderate: ≥50% (180°) - <75% (270°) of visible circumference C) Poor: <50% (180°) of visible circumference | Pre-PCI OCT Run procedure | 
| Number of Participants With Altered Clinical Decision Making on the Basis of the Post-stent Imaging Run | Clinical decision making will be assessed on the basis of the post-stent imaging run | During procedure, an average of 1 hour | 
| Median Intra-stent Lumen Area (Intra-stent Flow Area) | Intra-stent Lumen Area (Intra-stent Flow Area) is defined as stent area minus any protrusion | Up to 1 hour post-procedure | 
| Median Effective Lumen Area (Total Flow Area) | Effective lumen area (Total flow area) is defined as Intra-stent Lumen Area plus any area of malapposition between the stent and the vessel wall (lumen border/plaque border). | Up to 1 hour post-procedure | 
| IVUS Secondary Endpoints: Comparison of Number of Participants With Dissection IVUS vs. OCT Imaging (IVUS Arm Only) | Dissection (Major, Minimal, All) will be compared between IVUS and OCT Imaging cohorts | During procedure, an average of 1 hour | 
| IVUS Secondary Endpoints: Comparison of Number of Participants With Malapposition IVUS vs. OCT Imaging (IVUS Arm Only) | Malapposition (Major, Minimal, All) will be compared between IVUS and OCT Imaging cohorts | During procedure, an average of 1 hour | 
| IVUS Secondary Endpoints: Comparison of Number of Participants With Plaque or Thrombus Protrusion IVUS vs. OCT Imaging (IVUS Arm Only) | Protrusion (Major, Minimal, All) will be compared between IVUS and OCT Imaging cohorts | During procedure, an average of 1 hour | 
| Non OCT Secondary Endpoints - Angiographic Endpoints (QCA): Median Minimal Lumen Diameter | Angiographic Endpoints (QCA) will be assessed as Minimal lumen diameter | Baseline | 
| Non OCT Secondary Endpoints - Angiographic Endpoints (QCA): Median Minimal Lumen Diameter | Angiographic Endpoints (QCA) will be assessed as Minimal lumen diameter | Final Post-PCI, up to 1 hour after PCI procedure | 
| Non OCT Secondary Endpoints - Angiographic Endpoints (QCA): Median Diameter Stenosis | Angiographic Endpoints (QCA) will be assessed as diameter stenosis | Baseline | 
| Non OCT Secondary Endpoints - Angiographic Endpoints (QCA): Median Diameter Stenosis | Angiographic Endpoints (QCA) will be assessed as diameter stenosis | Final Post-PCI, up to 1 hour after PCI procedure | 
| Non OCT Secondary Endpoints (Angiographic Endpoints (QCA)) - Median Acute Lumen Gain Post-intervention | Angiographic Endpoints (QCA) will be assessed as Acute lumen gain post-intervention | Final Post-PCI, up to 1 hour after PCI procedure | 
| Non OCT Secondary Endpoints - Angiographic Endpoints (QCA): Median Maximum Stent Size/Reference Vessel Diameter Ratio | Angiographic Endpoints (QCA) will be assessed as Maximum stent size/reference vessel diameter ratio. Maximum stent size refers to the largest stent diameter used in a treated segment. If only one stent was used, it is that stent diameter. If more than one stent were used, it is the larger of the stent diameters. | Baseline | 
| Non OCT Secondary Endpoints - Angiographic Endpoints (QCA): Median Maximum Stent Size/Reference Vessel Diameter Ratio | Angiographic Endpoints (QCA) will be assessed as Maximum stent size/reference vessel diameter ratio. Maximum stent size refers to the largest stent diameter used in a treated segment. If only one stent was used, it is that stent diameter. If more than one stent were used, it is the larger of the stent diameters. | Final Post-PCI, up to 1 hour after PCI procedure | 
| Non OCT Secondary Endpoints - Angiographic Endpoints (QCA): Number of Participants With Angiographic Dissection ≥ NHLBI Type B | Angiographic Endpoints (QCA) will be assessed as Angiographic dissection ≥ NHLBI type B | Final Post-PCI, up to 1 hour after PCI procedure | 
| Procedural Endpoints (Site Reported): Median Total Stent Length | Median Total Stent Length will be measured in millimeters. | During procedure, an average of 1 hour | 
| Procedural Endpoints (Site Reported): Median Stents Per Lesion | Median Stents per lesion will be measured in counts | During procedure, an average of 1 hour | 
| Procedural Endpoints (Site Reported) - Median Maximal Stent Size | Median Maximal stent size will be measured in millimeters. | During procedure, an average of 1 hour | 
| Procedural Endpoints (Site Reported) - Median Post-dilatation Inflations | Post dilatation inflations will be assessed in terms of use of balloon inflations | During procedure, an average of 1 hour | 
| Procedural Endpoints (Site Reported): Median Maximum Inflation Pressure (Atm.) | Median Maximum inflation pressure will be measured in atm. | During procedure, an average of 1 hour | 
| Procedural Endpoints (Site Reported): Number of Participants With Additional Interventions | Participants will be analyzed for the use of additional inventions Additional interventions used on the basis of the post stent imaging run will be either use of Larger Balloon, Use of Higher Inflation Pressures, Use of Additional Inflations, Use of Additional Stent(s), Thrombus Aspiration, or Other Interventions | During procedure, an average of 1 hour | 
| Additional Procedural and Clinical Endpoints: Number of Participants With Angiography Defined Procedural Success Rate | Angiography defined procedural success rate is defined as a final lesion angiographic diameter stenosis <30% (QCA) and TIMI III flow (QCA) without dissection ≥ NHLBI type C, perforation, prolonged chest pain or ST segment elevation or depression changes (>30 minutes), or procedural death. | During procedure, an average of 1 hour | 
| Additional Procedural and Clinical Endpoints - Number of Participants With Device Success Rate | Device success rate (site reported): Successful OCT or IVUS imaging obtained pre and post PCI in the respective arms (does not include blinded OCT runs in the IVUS and Angiography arms) | During procedure, an average of 1 hour | 
| Additional Procedural and Clinical Endpoints - Number of Participants With Target Lesion Failure (TLF) | Target Lesion Failure (TLF) at 1 year defined as cardiovascular death, target vessel myocardial infarction, or ischemia driven target-lesion revascularization. Target lesion is defined as the lesion designated for randomization to OCT vs. IVUS vs. Angiography. | 1 year | 
| Additional Procedural and Clinical Endpoints - Number of Participants With Peri-procedural Myocardial Infarction | Number of Participants With Periprocedural Myocardial Infarction will be assessed at 1 year | 1 Year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Percutaneous Coronary Intervention, Intravascular Ultrasound, Optical Coherence Tomography, SJM-CIP-10034