Trial to Demonstrate the Safety and Effectiveness of the MiStent II for the Revascularization of Coronary Arteries.

Study Overview
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Brief Summary
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To compare MiStent to either the Xience or Promus stents.with the primary objective being to assess the safety and efficacy of the MiStent in a patient population requiring revascularization of de novo obstructive lesions of coronary arteries in patients with stable and unstable coronary artery disease (CAD) including non ST-Elevation Myocardial Infarction (NSTEMI)

Detailed Description
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The CRYSTAL study is a prospective, multi-center, randomized (1:1), single-blinded and controlled, investigational device exemption trial to test the non-inferiority of MiStent to commercially available everolimus drug eluting stents (Xience and Promus stents). Patients with coronary artery disease (CAD) that qualify for percutaneous coronary intervention (PCI) with stenting will be screened per the protocol inclusion and exclusion criteria.

Official Title
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CRYSTAL Study: A Multi-Center, Randomized, Controlled Trial to Demonstrate the Safety and Effectiveness of the MiStent II for the Revascularization of Coronary Arteries.

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: MiStent II coronary artery stent
* Device: Xience or Promus coronary artery stents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be ≥ 18 years of age Subject (or legal guardian) understands the trial requirements and the treatment procedures and provides written informed consent before any trial-specific tests or procedures are performed Subject is eligible for percutaneous coronary intervention (PCI) Subject has symptomatic coronary artery disease with objective evidence of ischemia or silent ischemia Subject is an acceptable candidate for coronary artery bypass grafting (CABG) Subject is willing to comply with all protocol-required follow-up evaluation Angiographic Inclusion Criteria (visual estimate): Target lesion(s) must be located in a native coronary artery with a visually estimated reference vessel diameter (RVD) ≥2.50 mm and ≤3.50 mm Target lesion(s) must be able to be treated with a single stent and the target lesion length must be ≤27 mm (by visual estimate). NOTE: Only lesion lengths that have both the control and comparable investigational stent lengths available at the same time are eligible for enrollment. Target lesion(s) must have visually estimated stenosis ≥50% and <100% with thrombolysis in Myocardial Infarction (TIMI) flow >1 and one of the following: Stenosis ≥70% or; Abnormal fractional flow reserve (FFR) defined as <0.80 or; Abnormal stress or imaging stress test or; Elevated biomarkers prior to the procedure Coronary anatomy is likely to allow delivery of a study device to the target lesions(s) The first lesion treated must be successfully predilated/pretreated Exclusion Criteria: Subject has clinical symptoms and/or electrocardiogram (ECG) changes consistent with acute ST elevation MI (STEMI) Subject has cardiogenic shock, hemodynamic instability requiring inotropic or mechanical circulatory support, intractable ventricular arrhythmias, or ongoing intractable angina Subject has received an organ transplant or is on a waiting list for an organ transplant Subject is receiving or scheduled to receive chemotherapy within 30 days before or after the index procedure Planned PCI (including staged procedures) or CABG after the index procedure Subject previously treated at any time with intravascular brachytherapy in the target vessel(s) Subject has a known allergy to contrast (that cannot be adequately premedicated) and/or the trial stent system or protocol-required concomitant medications (e.g., Cobalt-chromium alloy, stainless steel, everolimus or structurally related compounds, polymer or individual components, all P2Y12 inhibitors, or aspirin) Subject has one of the following (as assessed prior to the index procedure): Other serious medical illness (e.g., cancer, congestive heart failure) with estimated life expectancy of less than 24 months Current problems with substance abuse (e.g., alcohol, cocaine, heroin, etc.) Planned procedure that may cause non-compliance with the protocol or confound data interpretation Subject is receiving chronic (≥72 hours) anticoagulation therapy (i.e., heparin, coumadin, or other anticoagulation therapy) for indications other than acute coronary syndrome Subject has a platelet count <100,000 cells/mm3 or >700,000 cells/mm3 Subject has a white blood cell (WBC) count < 3,000 cells/mm3 Subject has documented or suspected liver disease, including laboratory evidence of hepatitis Subject is on dialysis or has baseline glomerular filtration rate (GFR) of <30 ml/min Subject has a history of bleeding diathesis, active peptic ulcer or gastrointestinal (GI) bleed, or coagulopathy or will refuse blood transfusions Subject has had a history of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within the past 6 months Subject has severe symptomatic heart failure (i.e., Left Ventricular Ejection Fraction (LVEF) <30%)) Subject is participating in another investigational drug or device clinical trial that has not reached its primary endpoint Subject intends to participate in another investigational drug or device clinical trial within 12 months after the index procedure Subject with known intention to procreate within 12 months after the index procedure (women of child-bearing potential who are sexually active must agree to use a reliable method of contraception from the time of screening through 12 months after the index procedure) Subject is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential) Angiographic Exclusion Criteria (visual estimate): Planned treatment of a single lesion with more than 1 stent Planned treatment of more than 3 lesions Planned treatment of lesions in more than 2 major epicardial vessels Planned treatment of more than 2 lesions in a single major epicardial vessel Subject has 2 target lesions in the same vessel that are separated by less than 15 mm (by visual estimate) Target lesion(s) is located in the left main or unprotected left Target lesion(s) is located within 3 mm of the origin of the left anterior descending (LAD) coronary artery or left circumflex (LCx) coronary artery by visual estimate Target lesion(s) is located within a saphenous vein graft or an arterial graft Target lesion(s) will be accessed via a saphenous vein graft or arterial graft Target lesion(s) with a TIMI flow 0 (total occlusion) or TIMI flow 1 prior to guide wire crossing Target lesion(s) treated during the index procedure that involves a complex bifurcation (e.g., bifurcation lesion requiring treatment with more than 1 stent) Target lesion(s) is restenotic from a previous stent implantation or study stent would overlap with a previous stent Subject has been treated with any type of PCI (i.e., balloon angioplasty, stent, cutting balloon atherectomy) within 24 hours prior to the index procedure Significant thrombus, present in the target vessel (by visual estimate)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: MiStent group vs. the Xience/Promus group.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MiStent II Coronary Artery Stent<br>Implantation of a coronary artery stent in an all-comers population, including patients with symptomatic coronary artery disease including patients with chronic stable angina, silent ischemia, and acute coronary syndromes, who qualify for percutaneous coronary interventions | Device: MiStent II coronary artery stent<br>* Implantation of a coronary stent patient with stable and unstable coronary artery disease including non-ST-Elevated Myocardial Infarction<br>|
| Active Comparator: Xience or Promus Coronary Artery Stents<br>Implantation of a coronary artery stent in an all-comers population, including patients with symptomatic coronary artery disease including patients with chronic stable angina, silent ischemia, and acute coronary syndromes, who qualify for percutaneous coronary interventions | Device: Xience or Promus coronary artery stents<br>* Implantation of a coronary stent patient with stable and unstable coronary artery disease including non-ST-Elevated Myocardial Infarction<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target Lesion Failure (TLF) | Any occurrence of Target Lesion Failure (TLF) TLF is defined as: Cardiac death, or Target vessel myocardial infarction (TV-MI, Q-wave and non Q-wave), or Ischemia driven target lesion revascularization. | through 12-month visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device success | Successful delivery and deployment of the study stent to the target vessel, without balloon rupture or stent embolization with post procedure diameter stenosis of < 30% (by visual estimation) in the Target Lesion. | Index Procedure | 
| Technical success | Achieving a final diameter stenosis of <30% (by visual estimation) in the target lesion using any combination of stents or devices allowed per protocol. | Index Procedure | 
| Procedural success | Post-procedure diameter stenosis <30% (by visual estimation) in all target lesions and the absence of in-hospital MI, TVR, or cardiac death. | Index Procedure | 
| Composite Endpoint POCE | POCE defined as all-cause death, any MI, or any revascularization | prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up | 
| Composite Endpoint MACE | MACE defined as all-cause death, any MI, or any TVR | prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up | 
| Composite Endpoint TVF | TVF defined as cardiac death, TV MI, or clinically indicated TVR | prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up | 
| Composite Endpoint TLF | TLF defined as cardiac death, TV MI or Ischemia driven TLR | prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up | 
| Mortality | Mortality including All death, Cardiac death, and Non-cardiac death (vascular and non-cardiovascular) | prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up | 
| Myocardial Infarction | Myocardial Infarction including All MI, TV-MI, and Non-TV-MI | prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up | 
| Revascularization | Revascularization including Target Lesion revascularization (TLR) (any, clinically- indicated TLR, non-clinically indicated TLR), Target Vessel revascularization (TVR) (any, clinically- indicated TVR, non-clinically indicated TVR), Non-TV revascularization, and Any revascularization | prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up | 
| Stent thrombosis rates | Stent thrombosis rates according to ARC classification: ST - Early (Acute, Sub-acute), Late, Very Late; ST - Definite, Probable, Possible | prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up | 
| Serious Adverse Events (SAEs) | All SAEs through 12 months' post-index procedure All device related SAEs from 12 months through 5 years' post-index procedure | prior to discharge, at 1-, 6- and 12-months and annually thereafter through 5 years' follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MiStent, Coronary Artery Disease, Coronary Disease, Myocardial Ischemia, Heart Disease, Cardiovascular Diseases, Arteriosclerosis, Arterial Occlusive Diseases, Vascular Diseases