Efficacy of Xience/Promus Versus Cypher in rEducing Late Loss After stENTing

Study Overview
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Brief Summary
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Objectives To evaluate the safety and long-term effectiveness of coronary stenting with the Everolimus-eluting coronary stent system(EECSS) (XIENCETM V, Abbott Vascular, Santa Clara, CA, PromusTM, Boston Scientific, Natick, MA), compared with the sirolimus-eluting coronary stent system(SECSS) (CypherTM, Cordis Johnson & Johnson, Warren, NJ) in the treatment of coronary stenosis. To evaluate the safety and efficacy of 6-month clopidogrel therapy compared with 12-month clopidogrel therapy. Study Design: Prospective, open label, two-arm, randomized multi-center trial to test the non-inferiority of EECSS compared with the SECSS, and to test the non-inferiority of 6 months duration compared with 12 months duration of clopidogrel therapy. Patients will be randomized in a two by two factorial manner according to the type of drug eluting stent (EECSS vs. SECSS) and the duration of dual anti-platelet therapy (6 months vs. 12 months). Randomization will also be stratified per hospital for the presence of DM and the presence of long lesions (lesion length ≥ 28mm) Patient Enrollment: 1,372 patients enrolled at 17 centers in Korea. Patient Follow-Up: Clinical follow-up will occur at 1, 3, and 9 months, and at 1, 2, 3, 4, and 5 years. Investigator or designee may conduct follow-up as telephone contacts or office visits. Primary Endpoint In-segment late luminal loss (LL) at 9 months for comparison of stenting with EECSS vs. SECSS. Target vessel failure (TVF) (cardiac death, myocardial infarction, ischemia driven target vessel revascularization) at 12 months for comparison of 6 months vs. 12 months of clopidogrel therapy Secondary Endpoint All Death Cardiac death Myocardial infarction Target vessel revascularization (TVR) (all and ischemia-driven) Target lesion revascularization (TLR) (all and ischemia-driven) Stent thrombosis Acute success (device, lesion, and procedure) Bleeding Cerebrovascular accident In-stent LL at 9 months Angiographic pattern of restenosis at 9-month angiographic follow-up In-stent and in-segment % diameter stenosis (%DS) at 9 months In-stent % volume obstruction (%VO) at 9 months Incomplete stent apposition post index procedure Persisting incomplete stent apposition, late-acquired incomplete stent apposition, aneurysm, thrombosis, and persisting dissection at 9 months

Official Title
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Comparison of the Efficacy of Everolimus-Eluting Versus Sirolimus-Eluting Stent for Coronary Lesions

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: Everolimus-eluting stent (Xience or Promus)
* Device: Sirolimus-eluting stent (Cypher)
* Drug: 6-month clopidogrel therapy
* Drug: 12-month clopidogrel therapy


Participation Criteria
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Eligibility Criteria
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General Inclusion Criteria: Subject must be at least 18 years of age. Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving the XIENCE V EECS and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure. Subject must have significant coronary artery stenosis (>50% by visual estimate) Subject must have evidence of myocardial ischemia (e.g., stable, unstable angina, recent infarction, silent ischemia, positive functional study or a reversible changes in the electrocardiogram (ECG) consistent with ischemia. In subjects with coronary artery stenosis > 75%, evidence of myocardial ischemia does not have to be documented. Subjects must be an acceptable candidate for Coronary Artery Bypass Graft (CABG) surgery. Angiographically Inclusion Criteria Target lesion(s) must be located in a native coronary artery with visually estimated diameter of ≥ 2.25 mm and ≤ 4.25 mm. Target lesion(s) must be amenable for percutaneous coronary intervention General Exclusion Criteria: The patient has a known hypersensitivity or contraindication to any of the following medications (heparin, aspirin, clopidogrel, sirolimus, everolimus, Contrast media Systemic (intravenous) Sirolimus, everolimus use within 12 months. Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions. Gastrointestinal or genitourinary bleeding within the prior 3 months, or major surgery within 2 months. Current known current platelet count <100,000 cells/mm3 or Hgb <10 g/dL. An elective surgical procedure is planned that would necessitate interruption of clopidogrel during the first 12 months post enrollment. Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment). Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period. Patients who have received any stent implantation in the target vessel prior to enrollment. Patients with LVEF<25% or those with cardiogenic shock Patients with myocardial infarction within 72 hours Creatinine level ≥ 3.0mg/dL or dependence on dialysis. Severe hepatic dysfunction (AST and ALT: 3 times upper normal reference values). Angiographic Exclusion Criteria Patients with significant left main coronary artery stenosis Patients who's target lesion has in-stent restenosis at the stented segment of drug-eluting stents or bare metal stents Target lesions with chronic total occlusion True bifurcation lesions requiring two stents

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E6<br>Everolimus-eluting stent 6-month clopidogrel therapy | Device: Everolimus-eluting stent (Xience or Promus)<br>* Use everolimus-eluting stent in the treatment of coronary stenosis<br>* Other names: Promus;Drug: 6-month clopidogrel therapy<br>* Use clopidogrel for 6 months<br>* Other names: Plavix;|
| Active Comparator: S6<br>Sirolimus-eluting stent 6-month clopidogrel therapy | Device: Sirolimus-eluting stent (Cypher)<br>* Use sirolimus-eluting stent in the treatment of coronary stenosis<br>* Other names: Cypher;Drug: 6-month clopidogrel therapy<br>* Use clopidogrel for 6 months<br>* Other names: Plavix;|
| Experimental: E12<br>Everolimus-eluting stent 12-month clopidogrel therapy | Device: Everolimus-eluting stent (Xience or Promus)<br>* Use everolimus-eluting stent in the treatment of coronary stenosis<br>* Other names: Promus;Drug: 12-month clopidogrel therapy<br>* Use clopidogrel for 12 months<br>* Other names: Plavix;|
| Active Comparator: S12<br>Sirolimus-eluting stent 12-month clopidogrel therapy | Device: Sirolimus-eluting stent (Cypher)<br>* Use sirolimus-eluting stent in the treatment of coronary stenosis<br>* Other names: Cypher;Drug: 12-month clopidogrel therapy<br>* Use clopidogrel for 12 months<br>* Other names: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-segment late luminal loss (LL) at 9 months for comparison of stenting with EECSS vs. SECSS. |  | 9 months | 
| Target vessel failure (TVF) (cardiac death, myocardial infarction, ischemia driven target vessel revascularization) at 12 months for comparison of 6 months vs. 12 months of clopidogrel therapy |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All death |  | 5 years | 
| Cardiac death |  | 5 Years | 
| Myocardial infarction |  | 5 years | 
| Target vessel revascularization (TVR) (all and ischemia-driven) |  | 5 years | 
| Target lesion revascularization (TLR) (all and ischemia-driven) |  | 5 years | 
| Stent thrombosis |  | 5 years | 
| Acute success (device, lesion, and procedure) |  | Index procedure | 
| Bleeding |  | 5 years | 
| Cerebrovascular accident |  | 5 years | 
| In-stent LL at 9 months |  | 9 months | 
| Angiographic pattern of restenosis at 9-month angiographic follow-up |  | 9 months | 
| In-stent and in-segment % diameter stenosis (%DS) at 9 months |  | 9 months | 
| In-stent % volume obstruction (%VO) at 9 months |  | 9 months | 
| Incomplete stent apposition post index procedure |  | Index procedure | 
| Persisting incomplete stent apposition, late-acquired incomplete stent apposition, aneurysm, thrombosis, and persisting dissection at 9 months |  | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Everolimus, Sirolimus, drug eluting stent, Clopidogrel