Zotarolimus and Everolimus-Eluting Stents ProsPectively Compared in Real World

Coronary Artery Disease Clinical Trial

— ZEPPELIN  

Official title:

Randomized Comparison of Zotarolimus- and Everolimus-Eluting Stents for Coronary Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00768846
• Other study ID #: GE IDE No. S03008
• Status: Recruiting
• Phase: Phase 4
• First received: October 6, 2008
• Last updated: October 11, 2008
• Start date: September 2008
• Est. completion date: June 2011

Study information

• Verified date: October 2008
• Source: Deutsches Herzzentrum Muenchen
• Contact: Julinda Mehilli, MD
• Phone: +49-1218
• Email: mehilli[@]dhm.mhn.de
• Is FDA regulated: No
• Health authority: Germany: German Institute of Medical Documentation and Information
• Study type: Interventional

Clinical Trial Summary

The zotarolimus-eluting Endeavor Resolute stent is not inferior to the everolimus- eluting Xience V stent platform regarding a composite of cardiac death, myocardial infarction or target lesion revascularisation in a real-world population.

Description:

The use of stents has become common practice in the percutaneous treatment of coronary artery disease. Restenosis affected 20-40% of de novo coronary lesions treated with bare metal stents. Drug-eluting stents (DES) have emerged as the most effective strategy for the prevention of restenosis. The first available DES were the Sirolimus-eluting Cypher and the Paclitaxel-eluting Taxus stent. Although their mid-term efficacy has been well-established, there is an ongoing debate on the potential of an increased incidence of late stent thrombosis, as well as of delayed onset of restenosis or catch-up phenomenon with DES. Recent evidence demonstrates that there might be differences between various DES in terms of safety and efficacy. The differences might be related to the drug, polymer or stent design. Everolimus (SDZ-RAD) and zotarolimus (ABT-578) are new antiproliferative agents that share some common structural and biological properties with sirolimus ("limus-group"). Both drugs bind to the intracellular sirolimus receptor, FK 506-binding protein 12 (FKBP 12). The drug-FKBP12 complex inhibits cell cycle progression via inactivation of the mammalian target of Rapamycin (mTOR) thereby regulating vascular smooth muscle cell migration and proliferation. Preclinical studies showed improved endothelialization and limited chronic inflammation of the everolimus-eluting stent compared with previous drug-eluting stents. Moreover, first randomized clinical trials of everolimus-eluting stents have shown promising results regarding safety, feasibility and efficacy in the suppression of neointimal proliferation. Safety and efficacy of the zotarolimus-eluting Endeavor stent have been investigated in the Endeavor clinical program. In the Endeavor III and IV trials, the Endeavour stent proved inferior to the Cypher and Taxus stents regarding angiographic endpoints. However, rates of target vessel failure were similar in both groups. The Endeavor RESOLUTE stent platform uses a new polymer with potential improvements of drug release compared to the Endeavor stent. The RESOLUTE clinical trial is the first-in man, observational, uncontrolled, non-randomized study evaluating the Endeavor Resolute drug-eluting stent with the new polymer. The trial enrolled a total of 130 patients with native coronary artery lesions. There are no data available comparing the zotarolimus-eluting Endeavor Resolute stent with the everolimus-eluting Xience V stent. Thus the aim of this prospective, randomized study is to compare the efficacy and safety of these two "new generation" drug-eluting stent platforms in a real world population.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2600
• Est. completion date: June 2011
• Est. primary completion date: May 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients older than 18 years with symptomatic coronary artery disease undergoing PCI with stent implantation.

• Written, informed consent by the patient or her/his legally-authorized representative for participation in the study.

Exclusion Criteria:

• Cardiogenic shock.

• Malignancies or other comorbid conditions (for example severe liver, renal and pancreatic disease) with life expectancy less than 12 months or that may result in protocol non-compliance.

• Known allergy to the study medications: everolimus, zotarolimus, cobalt chrome.

• Inability to take clopidogrel for at least 6 months.

• Pregnancy (present, suspected or planned) or positive pregnancy test. (In women with childbearing potential a pregnancy test is mandatory.)

• Previous enrollment in this trial.

• Patient's inability to fully cooperate with the study protocol.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Device:
• Endeavor Resolute Stent
Zotarolimus-eluting Endeavor Resolute Stent
• Xience V Stent
Everolimus-eluting Xience V Stent

Locations

Country	Name	City	State
Germany	1st Medizinische Klinik Klinikum rechts der Isar	Munich
Germany	Deutsches Herzzentrum Munich	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Deutsches Herzzentrum Muenchen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	A composite of cardiac death, myocardial infarction related to the target vessel or target lesion revascularisation		1 year after randomization	Yes
Secondary	Late luminal loss		6-8 months	No
Secondary	Binary angiographic restenosis		6-8 months	No
Secondary	All cause mortality		1 year	Yes
Secondary	Stent thrombosis		1 year	Yes