harmonizing optimal strategy for treatment of coronary artery stenosis - safety & effectiveness of drug-eluting stents & anti-platelet regimen

Conditions: Coronary Heart Disease

Summary: objectives 1. to compare the safety and long-term effectiveness of coronary stenting with the new platform everolimus-eluting coronary stenting system (eecss, promus element) compared with the zotarolimus-eluting coronary stenting system (zecss, endeavor resolute) in patients with coronary heart disease (chd) 2. to determine the short-term efficacy and safety of triple anti-platelet therapy (tat, aspirin 100mg qd, clopidogrel 75mg qd and cilostazol 100mg bid) compared with double-dose clopidogrel dual anti-platelet therapy (ddat, aspirin 100mg qd and clopidogrel 150mg qd) in patients undergoing percutaneous coronary intervention (pci) with drug-eluting stents (des) study design prospective, open-label, 2-by-2 multifactorial, randomized, multicenter trial to test the following in chd patients 1. non-inferiority of promus element stent compared with endeavor resolute stent in reducing target lesion failure (tlf) 2. non-inferiority of tat compared with ddat in reducing net clinical outcome patients will be randomized in a 2-by-2 factorial manner according to the type of drug eluting stent (eecss vs. zecss) and the type anti-platelet regimen (tat vs. ddat). randomization will also be stratified per presence of dm. patient enrollment 3750 patients enrolled at 50 centers in republic of korea patient follow-up clinical follow-up will occur at 1, 3, 12, 24, 36 months after the procedure. angiographical follow-up will be recommended to all participants at 13 months after the procedure. investigator or designee may conduct follow-up as telephone contacts or office visits. primary endpoint 1. target lesion failure (tlf), defined as a composite of cardiac death, target vessel-related myocardial infarction (mi) and ischemia-driven target lesion revascularization (tlr) up to 12 months for the stent arm 2. net clinical outcome, defined as a composite of cardiac death, nonfatal mi, cva and major bleeding by plato criteria at 1 month for the anti-platelet arm

secondary endpoint 1. clinical and laboratory endpoint at 1 month all death and cardiac death myocardial infarction (q wave and non-q wave) stent thrombosis (definite and possible) cva (hemorrhagic and non-hemorrhagic) bleeding (major and minor) verifynow asa and verifynow p2y12 2. clinical endpoint at 12 months all death and cardiac death target vessel-related mi and all mi (q wave and non-q wave) target vessel/lesion revascularization (ischemia-driven and all) stent thrombosis (definite/possible/probable) net clinical outcome including bleeding (major and minor) acute success of procedure (device, lesion and procedure) 3. angiographic (including ivus or oct) endpoint at 13 months in-stent \& in-segment late loss in-stent \& in-segment % diameter stenosis angiographic pattern of restenosis neointimal volume, % neointimal volume and % volume obstruction on ivus or oct degree of stent strut endothelialization on oct

Eligibility criteria:
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 promus element or endeavor resolute stents, and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure. * subject must have significant lesion (\>50% by visual estimate) in any of the coronary arteries, venous or arterial bypass grafts. * 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 diameter stenosis \> 70%, evidence of myocardial ischemia does not have to be documented. angiographic inclusion criteria * target lesion(s) must be located in coronary artery, venous or arterial bypass graft with diameter of ≥ 2.5 mm and ≤ 4.00 mm. * target lesion(s) must be amenable for percutaneous coronary intervention. exclusion criteria * the patient has a known hypersensitivity or contraindication to any of the following medications: heparin, aspirin, clopidogrel, cilostazol, everolimus, zotarolimus, contrast media (patients with documented sensitivity to contrast media which can be effectively premedicated with steroids and diphenhydramine \[e.g. rash\] may be enrolled. those with true anaphylaxis to prior contrast media, however, should not be enrolled.) * systemic (intravenous) everolimus or zotarolimus 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, known coagulopathy (including heparin-induced thrombocytopenia), abnormal hemogram (hb\<10g/dl or plt count \<100,000/μl) or will refuse blood transfusions * patients with severe lv systolic dysfunction (lvef\<25%) or cardiogenic shock * gastrointestinal or genitourinary bleeding within the prior 3 months, or major surgery within 2 months. * 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. * symptomatic heart failure

Keywords: everolimus zotarolimus cilostazol clopidogrel