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

NCT ID: NCT00418067

Last Updated: 2012-08-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

2645 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-10-31

Study Completion Date

2009-01-31

Brief Summary

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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

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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.

Conditions

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Coronary Artery Disease

Keywords

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Coronary Artery Disease Stent

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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Cypher

Sirolimus-eluting stent

Group Type ACTIVE_COMPARATOR

Cypher

Intervention Type DEVICE

Sirolimus-eluting stent

Taxus Liberte

Paclitaxel-eluting stent

Group Type ACTIVE_COMPARATOR

Taxus Liberte

Intervention Type DEVICE

Paclitaxel-eluting stent

Endeavor

Zotarolimus-eluting stent

Group Type EXPERIMENTAL

Endeavor

Intervention Type DEVICE

Zotarolimus-eluting stent

Interventions

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Endeavor

Zotarolimus-eluting stent

Intervention Type DEVICE

Cypher

Sirolimus-eluting stent

Intervention Type DEVICE

Taxus Liberte

Paclitaxel-eluting stent

Intervention Type DEVICE

Other Intervention Names

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Zotarolimus-eluting stent Sirolimus-eluting stent Paclitaxel-eluting stent

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medtronic Vascular

INDUSTRY

Sponsor Role collaborator

Seung-Jung Park

OTHER

Sponsor Role lead

Responsible Party

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Seung-Jung Park

Comparison of the Efficacy of Zotarolimus(ABT 578)-Eluting Stent versus Sirolimus-Eluting Stent versus Paclitaxel-Eluting Stent for Coronary Lesions: The Prospective, Randomized, and Multi-center Trial

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Seung-Jung Park, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine

Locations

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Soonchunhyang University Bucheon Hospital

Bucheon-si, , South Korea

Site Status

Daegu Catholic University Medical Center

Daegu, , South Korea

Site Status

Keimyung University Dongsan Medical Center

Daegu, , South Korea

Site Status

Kyungpook National University Hospital

Daegu, , South Korea

Site Status

Chungnam National University Hospital

Daejeon, , South Korea

Site Status

Asan Medical Center

Gangneung, , South Korea

Site Status

Chonnam National University Hospital

Gwangju, , South Korea

Site Status

NHIC Ilsan Hospital

Ilsan, , South Korea

Site Status

Chonbuk National University Hospital

Jeonju, , South Korea

Site Status

Pusan Natioanal University Hospital

Pusan, , South Korea

Site Status

Hallym University Sacred Heart Hospital

Pyeongchon, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Korea University Hospital

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

St.Mary's Catholic Medical Center

Seoul, , South Korea

Site Status

Yonsei University Medical Center

Seoul, , South Korea

Site Status

Ajou University Hospital

Suwon, , South Korea

Site Status

Ulsan University Hospital

Ulsan, , South Korea

Site Status

Yonsei University Wonju Christian Hospital

Wŏnju, , South Korea

Site Status

Countries

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South Korea

References

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Kang SJ, Mintz GS, Park DW, Lee SW, Kim YH, Lee CW, Han KH, Kim JJ, Park SW, Park SJ. Comparison of zotarolimus-eluting stents with sirolimus-eluting and paclitaxel-eluting stents: intimal hyperplasia and vascular changes assessed by volumetric intravascular ultrasound analysis. Circ Cardiovasc Interv. 2011 Apr 1;4(2):139-45. doi: 10.1161/CIRCINTERVENTIONS.110.957936. Epub 2011 Mar 1.

Reference Type DERIVED
PMID: 21364151 (View on PubMed)

Park DW, Kim YH, Yun SC, Kang SJ, Lee SW, Lee CW, Park SW, Seong IW, Lee JH, Tahk SJ, Jeong MH, Jang Y, Cheong SS, Yang JY, Lim DS, Seung KB, Chae JK, Hur SH, Lee SG, Yoon J, Lee NH, Choi YJ, Kim HS, Kim KS, Kim HS, Hong TJ, Park HS, Park SJ. Comparison of zotarolimus-eluting stents with sirolimus- and paclitaxel-eluting stents for coronary revascularization: the ZEST (comparison of the efficacy and safety of zotarolimus-eluting stent with sirolimus-eluting and paclitaxel-eluting stent for coronary lesions) randomized trial. J Am Coll Cardiol. 2010 Oct 5;56(15):1187-95. doi: 10.1016/j.jacc.2010.03.086.

Reference Type DERIVED
PMID: 20883925 (View on PubMed)

Other Identifiers

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2006-0136

Identifier Type: -

Identifier Source: org_study_id