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Zotarolimus-Eluting Stent Versus Sirolimus-Eluting Stent and PacliTaxel-Eluting Stent for Coronary Lesions

Phase 4
Completed
Conditions
Coronary Artery Disease
Interventions
Device: Cypher
Device: Taxus Liberte
Device: Endeavor
Registration Number
NCT00418067
Lead Sponsor
Seung-Jung Park
Brief Summary

The purpose of this study is to establish the safety and long-term effectiveness of coronary stenting with the ABT 578-eluting balloon expandable stent (Medtronic, Minneapolis, MN) vs. the sirolimus-eluting balloon expandable stent (Cordis Johnson \& Johnson, Warren, New Jersey) and the paclitaxel-eluting stent (Taxus liberte, Boston Scientific) for the treatment of coronary stenosis in routine clinical practice.

Detailed Description

Previous studies have documented that a slow-release polymeric sirolimus-eluting stent (Cypher, Cordis) and paclitaxel-eluting stent (Taxus, Boston Scientific) reduce neointimal formation and result in decrease of angiographic restenosis and target lesion revascularization at 1-3 years in the multicenter randomized clinical trials RAVEL, SIRIUS, and TAXUS I-VI.From these studies, the two leading drug-eluting stents (DESs) of the Cypher and Taxus have been widely and rapidly accepted as a standard treatment of coronary lesions.

Recently, randomized studies were conducted to reveal different outcomes of the different two DESs. These studies showed that the sirolimus-eluting stent was better than the paclitaxel-eluting stent in terms of lower angiographic restenosis rate or the two DESs were similar in angiographic outcomes. A recent meta-analysis supported results of the former randomized studies. Patients receiving sirolimus-eluting stent had a significantly lower risk of restenosis and target vessel revascularization compared with those receiving paclitaxel-eluting stent.

With a recent approval of new DES, ABT-578-eluting stent (Endeavor, Medtronic, Minneapolis, MN), other comparison studies have been conducted to compare Endeavor ABT-578-eluting stent with the sirolimus-eluting stent and paclitaxel-eluting stent. ABT-578 and sirolimus share some common structural and biological properties. The ENDEAVOR clinical trials are currently in progress to evaluate a phosphoryl choline (PC)-coated ABT-578-eluting stent for the prevention of restenosis. The Endeavor ABT-578-eluting stent utilizes a cobalt alloy balloon-expandable stent (Driver; Medtronic) with a geometry similar to the stainless steel stent used in this preliminary study (S7; Medtronic). The Endeavor ABT-578-eluting stent also employees a PC strut surface coating as the drug delivery reservoir with a dose of 10 ug/mm of ABT-578. The Endeavor ABT-578-eluting stent, however, differs from the stent used in this experimental study by the addition of a drug-free PC coating to serve as a diffusion barrier to retard drug release from the polymer reservoir. Angiographic analysis at 4 months in the 100-patient focal de novo lesion ENDEAVOR I feasibility study demonstrated a mean in-stent percent diameter stenosis of approximately 14% and a late lumen loss of 0.3 mm with a low frequency of target lesion revascularization (1%). The clinical outcomes from the ENDEAVOR II (1,500 patients randomized to ABT-578 or bare metal stent) and the ENDEAVOR III (436 patients randomized 3:1 to ABT-578 or Cypher) trials as well as other ongoing studies showed efficacy of the PC-coated ABT-578-eluting stent. In ENDEAVOR III study, the Endeavor stent had larger late loss and higher binary restenosis in both the analysis segment and stented segment. In contrast, the TLR rates are not statistically different between the Endeavor (6.0%) and the Cypher (5.3%, p=1.0) stents. This result of this study raised several questions to warrant further randomized studies 1) is the angiographic superiority of Cypher stent applied to the more complex lesions, 2) why is the TLR rate similar in spite of significantly different angiographic outcomes, 3) which is better in the Endeavor and the Taxus stents, etc. The ENDEAVOR IV study is being conducted to compare the safety and efficacy of the Endeavor stent versus the Taxus stent. However, the inclusion of ENDEAVOR IV study was also limited that this study did not include all complex lesions. Because of the limitations of current ENDEAVOR series, a further large randomized study for the concurrent comparison of the three DESs in the treatment of real-world practice would be needed.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2645
Inclusion Criteria
  • The patient must be at least 18 years of age.
  • Significant coronary artery stenosis (>50% by visual estimate)
  • Patients with stable (CCS class 1 to 4) or acute coronary syndromes (unstable angina pectoris class IB, IC, IIB, IIC, IIIB, IIIC or NSTEMI) or patients with atypical chest pain or without symptoms but having documented myocardial ischemia, amenable to stent-assisted percutaneous coronary intervention
  • The patient or guardian agrees to the study protocol and the schedule of clinical and angiographic follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site.
Exclusion Criteria
  • The patient has a known hypersensitivity or contraindication to any of the following medications:

    • Heparin, Aspirin, Both Clopidogrel and Ticlopidine, Sirolimus, paclitaxel, ABT 578, Stainless steel and/or Contrast media (patients with documented sensitivity to contrast which can be effectively pre-medicated with steroids and diphenhydramine [e.g. rash] may be enrolled. Patients with true anaphylaxis to prior contrast media, however, should not be enrolled).

  • Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study.

  • 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 antiplatelet drugs 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 target lesion of in-stent restenosis at the stented segment of drug-eluting stent (in-stent restenosis of bare metal stent can be included).

  • Patients with EF<30%.

  • Patients with cardiogenic shock

  • Acute STEMI patients within symptom onset < 12 hours needing primary angioplasty

  • Creatinine level > 3.0mg/dL or dependence on dialysis.

  • Severe hepatic dysfunction (AST and ALT > 3 times upper normal reference values).

  • Patients with left main stem stenosis (>50% by visual estimate)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CypherCypherSirolimus-eluting stent
Taxus LiberteTaxus LibertePaclitaxel-eluting stent
EndeavorEndeavorZotarolimus-eluting stent
Primary Outcome Measures
NameTimeMethod
The composite of death (all cause-mortality), myocardial infarction, and ischemia-driven target vessel revascularizationat 12 months after the index procedure
Secondary Outcome Measures
NameTimeMethod
All-cause DeathIn-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years
Cardiac deathIn-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years
Myocardial infarctionIn-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years
Target vessel revascularization (all and ischemia-driven)In-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years
Target lesion revascularization (all and ischemia-driven)In-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years
Stent thrombosis by definition of Academic Research Consortium (ARC)In-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years
Late luminal loss in both in-stent and in-segmentat 8 month angiographic follow-up
Binary restenosis in both in-stent and in-segmentAt 8 month angiographic follow-up
Procedural success defined as achievement of a final diameter stenosis of <30% by QCA using any percutaneous method, without the occurrence of death, Q wave MI, or urgent revascularization during the hospital stay.In-hospital

Trial Locations

Locations (19)

Chonnam National University Hospital

🇰🇷

Gwangju, Korea, Republic of

Daegu Catholic University Medical Center

🇰🇷

Daegu, Korea, Republic of

Keimyung University Dongsan Medical Center

🇰🇷

Daegu, Korea, Republic of

Chonbuk National University Hospital

🇰🇷

Jeonju, Korea, Republic of

Chungnam National University Hospital

🇰🇷

Daejeon, Korea, Republic of

Soonchunhyang University Bucheon Hospital

🇰🇷

Bucheon, Korea, Republic of

Kyungpook National University Hospital

🇰🇷

Daegu, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Seoul National University Bundang Hospital

🇰🇷

Seongnam, Korea, Republic of

Pusan Natioanal University Hospital

🇰🇷

Pusan, Korea, Republic of

Korea University Hospital

🇰🇷

Seoul, Korea, Republic of

NHIC Ilsan Hospital

🇰🇷

Ilsan, Korea, Republic of

Hallym University Sacred Heart Hospital

🇰🇷

PyeongChon, Korea, Republic of

Yonsei University Wonju Christian Hospital

🇰🇷

Wonju, Korea, Republic of

Ajou University Hospital

🇰🇷

Suwon, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Ulsan University Hospital

🇰🇷

Ulsan, Korea, Republic of

St.Mary's Catholic Medical Center

🇰🇷

Seoul, Korea, Republic of

Yonsei University Medical Center

🇰🇷

Seoul, Korea, Republic of

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