Zotarolimus-Versus Sirolimus-Versus PacliTaxel-Eluting Stent for Acute Myocardial Infarction Patients (ZEST-AMI)

This study has been terminated.
(The recruitment rate was much slower than expected.)
Sponsor:
Collaborator:
Cordis Corporation
Information provided by:
CardioVascular Research Foundation, Korea
ClinicalTrials.gov Identifier:
NCT00422565
First received: January 16, 2007
Last updated: January 30, 2009
Last verified: January 2009
  Purpose

The trial has the following primary objective:

To compare the safety and effectiveness of primary acute MI intervention with ABT 578-eluting balloon expandable stent (Medtronic, Minneapolis, MN) vs. sirolimus-eluting balloon expandable stent (Cordis Johnson & Johnson, Warren, New Jersey) vs. paclitaxel-eluting stent (Taxus Liberte, Boston Scientific).


Condition Intervention Phase
Myocardial Infarction
Device: Endeavor, Medtronic
Device: Cypher, Cordis
Device: Taxus Liberte, Boston Scientific
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 Safety of Zotarolimus-Eluting Stent Versus Sirolimus-Eluting Stent Versus PacliTaxel-Eluting Stent for Acute Myocardial Infarction Patients

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), MI (Q wave and non Q wave) 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: 1 month, 6 month, 1 year and thereafter annaully up to 5 years ] [ Designated as safety issue: Yes ]
  • Cardiac death [ Time Frame: 1 month, 6 month, 1 year and thereafter annaully up to 5 years ] [ Designated as safety issue: Yes ]
  • Recurrent Myocardial infarction [ Time Frame: 1 month, 6 month, 1 year and thereafter annaully up to 5 years ] [ Designated as safety issue: Yes ]
  • Target vessel revascularization (all and ischemia-driven) [ Time Frame: 1 month, 6 month, 1 year and thereafter annaully up to 5 years ] [ Designated as safety issue: No ]
  • Target lesion revascularization (all and ischemia-driven) [ Time Frame: 1 month, 6 month, 1 year and thereafter annaully up to 5 years ] [ Designated as safety issue: No ]
  • Stent thrombosis for the patients [ Time Frame: 1 month, 6 month, 1 year and thereafter annaully up to 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 repeat revascularization of the target lesion [ Time Frame: during the hospital stay ] [ Designated as safety issue: Yes ]

Enrollment: 328
Study Start Date: October 2006
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Endeavor
Zotarolimus-eluting stent
Device: Endeavor, Medtronic
Zotarolimus-eluting stent
Other Name: Zotarolimus-eluting stent
Active Comparator: Cypher
Sirolimus-eluting stent
Device: Cypher, Cordis
Sirolimus-eluting stent
Other Name: Sirolimus-eluting stent
Active Comparator: Taxus
Paclitaxel-eluting stent
Device: Taxus Liberte, Boston Scientific
Paclitaxel-eluting stent
Other Name: Paclitaxel-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. The ENDEAVOR clinical trials are currently in progress to evaluate a phosphoryl choline (PC)-coated ABT-578-eluting stent for the prevention of restenosis. 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 (1,197 patients randomized to ABT-578 or bare metal stent) showed superior efficacy of the PC-coated ABT-578-eluting stent than bare-metal stent.

In patients with acute myocardial infraction (MI), routine stent implantation has been shown to have a better procedural success rate and clinical outcome than balloon angioplasty [11]. However, restenosis and vessel reocclusion remain major challenges limiting the long-term success of percutaneous treatment.

In a clinical study of 400 patients with stent implantation in acute MI, angiographic restenosis occurred in 31%, considerably more than expected for patients with stable coronary disease. There is very little information available as to the efficacy and long-term safety of DES in acute MI. The results from the several registry and randomized trials (Cypher-AMI, Typhoon, PASSION) demonstrated the short-term or long-term safety and efficacy of DES compared to BMS.

The incomplete evidence to date is that implantation of SES in patients with Acute MI is safe and effective more than BMS and results of implantation of PES are at variance with the results of the BMS. However, up to date, there are randomized trials to compare the efficacy and safety among commonly used DES (zotarolimus- vs. sirolimus- vs. paclitaxel-eluting stents) for the treatment of acute MI patients. The results of large randomized trials and larger registries will allow us to make evidence-based decisions about which stent to use in patients with acute MI. Therefore, we designed a randomized, controlled, partially blinded trial comparing the safety and efficacy of the zotarolimus vs. sirolimus vs. paclitaxel stents in acute MI patients undergoing percutaneous coronary intervention.

  Eligibility

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

Inclusion Criteria:

  1. The patient must be at least 18 years of age.
  2. Culprit de novo lesion in a native coronary artery with significant stenosis (>50% by visual estimate) eligible for stent implantation (no limitation on stent length)
  3. Prolonged, continuous (≥ 20 min) chest pain despite nitrate and: (1) at least 1mm ST-segment elevation in at least 2 leads or reciprocal ST-segment depression ≥ 2 contiguous precordial leads, or (2) newly developed left bundle branch block
  4. Symptoms < 12 hours
  5. 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:

  1. 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).
  2. Systemic (intravenous) Sirolimus, paclitaxel or ABT-578 use within 12 months.
  3. Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study.
  4. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions.
  5. Fibrinolytic therapy for current MI treatment
  6. Previous coronary intervention on target vessel
  7. 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).
  8. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.
  9. Previously documented LVEF <30%.
  10. Evident cardiogenic shock before randomization
  11. Patients with left main stem stenosis (>50% by visual estimate)
  12. Severe calcification or tortuosity
  13. Multi-vessel disease with non-culprit vessel requiring bypass surgery
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00422565

Locations
Korea, Republic of
Soonchunhyang University Bucheon Hospital
Bucheon, Korea, Republic of
Daegu Catholic University 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
Pusan Natioanal University Hospital
Pusan, Korea, Republic of
Korea University Hospital
Seoul, Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-732
St. Mary's Catholic Medical Center
Seoul, Korea, Republic of
Ulsan University Hospital
Ulsan, Korea, Republic of
Yonsei University Wonju Christian Hospital
Wonju, Korea, Republic of
Sponsors and Collaborators
CardioVascular Research Foundation, Korea
Cordis Corporation
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

Responsible Party: Seung-Jung Park, Asan Medical Center
ClinicalTrials.gov Identifier: NCT00422565     History of Changes
Other Study ID Numbers: 2006-0137
Study First Received: January 16, 2007
Last Updated: January 30, 2009
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

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

Additional relevant MeSH terms:
Infarction
Myocardial Infarction
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Cardiovascular 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 April 17, 2014