Zotarolimus-Eluting Stent Versus Sirolimus-Eluting Stent and PacliTaxel-Eluting Stent for Coronary Lesions (ZEST)

This study has been completed.
Sponsor:
Collaborator:
Medtronic Vascular
Information provided by (Responsible Party):
Seung-Jung Park, CardioVascular Research Foundation, Korea
ClinicalTrials.gov Identifier:
NCT00418067
First received: January 3, 2007
Last updated: August 20, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Device: Endeavor
Device: Cypher
Device: Taxus Liberte
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Comparison of the Efficacy and the Safety of Zotarolimus-Eluting Stent Versus Sirolimus-Eluting Stent and PacliTaxel-Eluting Stent for Coronary Lesions

Resource links provided by NLM:


Further study details as provided by CardioVascular Research Foundation, Korea:

Primary Outcome Measures:
  • The composite of death (all cause-mortality), myocardial infarction, and ischemia-driven target vessel revascularization [ Time Frame: at 12 months after the index procedure ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • All-cause Death [ Time Frame: In-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years ] [ Designated as safety issue: Yes ]
  • Cardiac death [ Time Frame: In-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years ] [ Designated as safety issue: Yes ]
  • Myocardial infarction [ Time Frame: In-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years ] [ Designated as safety issue: Yes ]
  • Target vessel revascularization (all and ischemia-driven) [ Time Frame: In-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years ] [ Designated as safety issue: No ]
  • Target lesion revascularization (all and ischemia-driven) [ Time Frame: In-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years ] [ Designated as safety issue: No ]
  • Stent thrombosis by definition of Academic Research Consortium (ARC) [ Time Frame: In-hospital, 30 days, 6 months, 1 year, and thereafter annually upto 5 years ] [ Designated as safety issue: Yes ]
  • Late luminal loss in both in-stent and in-segment [ Time Frame: at 8 month angiographic follow-up ] [ Designated as safety issue: No ]
  • Binary restenosis in both in-stent and in-segment [ Time Frame: At 8 month angiographic follow-up ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: In-hospital ] [ Designated as safety issue: Yes ]

Enrollment: 2645
Study Start Date: October 2006
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Cypher
Sirolimus-eluting stent
Device: Cypher
Sirolimus-eluting stent
Other Name: Sirolimus-eluting stent
Active Comparator: Taxus Liberte
Paclitaxel-eluting stent
Device: Taxus Liberte
Paclitaxel-eluting stent
Other Name: Paclitaxel-eluting stent
Experimental: Endeavor
Zotarolimus-eluting stent
Device: Endeavor
Zotarolimus-eluting stent
Other Name: Zotarolimus-eluting stent

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00418067

Locations
Korea, Republic of
Soonchunhyang University Bucheon Hospital
Bucheon, Korea, Republic of
Kyungpook National University Hospital
Daegu, Korea, Republic of
Daegu Catholic University Medical Center
Daegu, Korea, Republic of
Keimyung University Dongsan Medical Center
Daegu, Korea, Republic of
Chungnam National University Hospital
Daejeon, Korea, Republic of
Asan Medical Center
GangNeung, Korea, Republic of
Chonnam National University Hospital
Gwangju, Korea, Republic of
NHIC Ilsan Hospital
Ilsan, Korea, Republic of
Chonbuk National University Hospital
Jeonju, Korea, Republic of
Pusan Natioanal University Hospital
Pusan, Korea, Republic of
Hallym University Sacred Heart Hospital
PyeongChon, Korea, Republic of
Seoul National University Bundang Hospital
Seongnam, Korea, Republic of
St.Mary's Catholic Medical Center
Seoul, Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of
Yonsei University Medical Center
Seoul, Korea, Republic of
Korea University Hospital
Seoul, Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Ajou University Hospital
Suwon, Korea, Republic of
Ulsan University Hospital
Ulsan, Korea, Republic of
Yonsei University Wonju Christian Hospital
Wonju, Korea, Republic of
Sponsors and Collaborators
Seung-Jung Park
Medtronic Vascular
Investigators
Principal Investigator: Seung-Jung Park, MD, PhD Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine
  More Information

No publications provided by CardioVascular Research Foundation, Korea

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: 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, CardioVascular Research Foundation, Korea
ClinicalTrials.gov Identifier: NCT00418067     History of Changes
Other Study ID Numbers: 2006-0136
Study First Received: January 3, 2007
Last Updated: August 20, 2012
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by CardioVascular Research Foundation, Korea:
Coronary Artery Disease
Stent

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Sirolimus
Everolimus
Paclitaxel
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 24, 2014