Comparative Phase IV Study: Efficacy And Safety of TiTAN2 Versus COBALT-CHROME Stents- EVIDENCEII

Study Overview
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Brief Summary
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The purpose of this study is to compare the effectiveness and safety, at 24 months, of the TITAN2 stent to any bare-metal stent (BMS) in Cobalt-Chromium in a population presenting an indication for these stents among 40% of which present an acute coronary syndrome (ACS).

Detailed Description
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The EVIDENCE II trial is a post-registration study for TITAN2 stent initiated on the request of the French Health Authorities' (HAS) in June 2009 for the next renewal of registration on the list of reimbursable products and services in France. The study is so designed to compare the effectiveness and safety at 24 months of the TiTAN2 versus Cobalt-Chromium BMS randomly assigned. As a part of the secondary objectives, a cost-effectiveness study is also planned. The comparators are cobalt chromium stents CE marketed and free of any coating (nude BMS). All will be used in their authorized indications. A total of 1350 patients will be included over a period of a year or more and followed for 24 months for the primary endpoint (MACE rate at 24 months in the overall population : cumulative incidence of cardiac deaths, MI and target lesion revascularization (TLR)). Patients will also be clinically followed at 6 and 12 months . Medico economic datas are to collect at a similar time point. An independent Clinical Event Committee, unaware of the treatment allocation, will be in charge of the adjudication of all the cardiac events including MACE (main objective)collected. The calculation of the number of subjects specifies that 1350 patients are needed to meet the primary endpoint of the study. Enrolled patient will be randomly assigned in a 2:1 fashion as follows : 900 patients in TITAN2 arm including 360 with ACS (Arm A) 450 patients in Cobalt-chromium arm including 180 with ACS (Arm B) In case of more than one stent needed, the protocol mandated using the same stent than the one assigned in all the lesions treated.

Official Title
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A French, Multicentric, Randomized, Simple Blind, Superiority Study Comparing the Efficiency and the Safety at 24 Months of the Stent Titan2 Versus Bare Metal Stent in Cobalt-Chrome in All Comers Patients Among Which 40 % Present an ACS.

Conditions
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Silent Myocardial Infarction, Stable Angina, Acute Coronary Syndrome

Intervention / Treatment
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* Device: Titan 2 stents
* Device: Cobalt-Chromium Bare Metal Stents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with symptomatic de novo coronary lesion involving one or two vessels Patient presenting a lesion with > 50% stenosis Patient who must undergo a percutaneous coronary intervention (PCI) in the indications of Cobalt-chromium bare metal stents and TITAN2 stents and being able to be indifferently treated with one or the other of these stents. Written informed consent Expected survival > 2 years Patient reachable by phone throughout the duration of the study. Exclusion Criteria: Pregnant/Lactating women Women of childbearing potential (last menstrual period <12 months) not using effective contraception Patient under legal protection Indication of coronary artery bypass graft surgery (CABG) History of coronary artery bypass graft surgery (CABG) Intrastent restenosis lesion Bifurcation lesion with the exception of those treated with a standardized approach (provisional stenting with final kissing in the side branch) Left main coronary lesion Ostial target lesion Previous drug-eluting stenting Previous bare metal stenting or balloon angioplasty in the 12 months prior the inclusion; if this implantation involved the target artery, separate the new implanted stent at a distance ≥ 10 mm. History of stent thrombosis Heavily calcified lesion Use of the Rotablator Left ventricular ejection fraction (LVEF) < 30% Cardiac arrest, cardiogenic shock or severe heart failure (Killip stage III or IV) Severe chronic renal failure (creatinine clearance <30 ml min) Cardiac or renal transplantation Major surgery within the last 14 days Surgery scheduled within 30 days (non-ACS patients) or 12 months (if ACS) at the time of the randomization History of major bleeding Pathology with major risk of bleeding or any condition, allergy or intolerance which is incompatible with anticoagulation and / or extended antiplatelet therapy Known allergy to Titanium, Nickel, Cobalt or Chromium Patient currently participating in another clinical trial Non-compliant patient (treatment and follow-up) Patient living abroad

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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TITAN 2 stent - Hexacath France<br>Patients receiving Titan 2 stents (percutaneous coronary intervention) | Device: Titan 2 stents<br>* The intervention is called Percutaneous Coronary Intervention (PCI); Commonly known as coronary angioplasty or simply angioplasty, it is a non-surgical procedure used to treat the stenotic (narrowed) coronary arteries of the heart found in coronary heart disease. PCI is usually performed by an interventional cardiologist.<br>|
| Active Comparator: Cobalt-Chromium BMS - Any firm<br>Patients receiving Cobalt-Chromium Bare Metal Stents (free of any coating)(percutaneous coronary intervention) | Device: Cobalt-Chromium Bare Metal Stents<br>* The intervention is called Percutaneous Coronary Intervention (PCI); Commonly known as coronary angioplasty or simply angioplasty, it is a non-surgical procedure used to treat the stenotic (narrowed) coronary arteries of the heart found in coronary heart disease. PCI is usually performed by an interventional cardiologist.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MACE | The primary endpoint (MACE) is the composite of cardiac death, (Myocardial Infarction) MI and target lesion revascularization (TLR). These events will be collected post-procedure during the patient's hospitalization and at 6 , 12 and 24 month follow-up. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medico economic evaluation | Data collection of acts and diagnosis specific codes related to any adverse event with hospitalization in relation with the endoprothesis allocated. It will be then analyzed by an dedicated expert who will be able to appreciate a cost/efficiency rate for each treatment arm. | 24 months | 
| Target Lesion Revascularization (TLR ) rate | Any study stent restenosis leading to a procedure or a surgery to treat it. | 24 months | 
| Stent thrombosis rate | Stent thrombosis will be evaluated as per the ARC classification (ie degree of evidence and time to event) | 24 months | 
| Success of the procedure | Defined as an efficient reintroduction of the blood flow in the target vessel post angioplasty. It's a YES/NO question. | 24 months |