The Efficacy of Three Different Limus Agent-Eluting Stents to Prevent Restenosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of 3 different drug-eluting-stent platforms to reduce coronary artery reblockage after stent implantation

Detailed Description
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Coronary artery reblockage remains still a drawback of percutaneous coronary interventions even in the era of drug-eluting stents (DES). DESs working principle consists of the delivery of controlled amounts of antiproliferative agents at the local level, which results in the suppression of neontimal proliferation, the main cause of lumen re-narrowing after stent implantation.At present, several DES platforms have been developed and evaluated for clinical use. They differ between them with regard to the stent type, anti-proliferative drug, presence of polymers employed for drug storage and modification of drug-release kinetics as well as type of polymer used for this purpose. Most of the DES platforms have used agents from the limus family. Although the majority of DESs employ polymer coating to control drug storage and release, in view of the increasing safety and efficacy associated with the long-term presence of polymers a strong interest has recently been shown in the development DES platforms that do not require permanent polymers. Trials as ACTION or JUPITER II have demonstrated that not all DESs are associated with the expected improved outcomes. On the other hand, not all successful DESs have been equally effective in the reduction of restenosis. Thus, rapamycin-eluting stents (Cypher stents) have been associated with lower angiographic and clinical restenosis rates than paclitaxel-eluting stents (Taxus stents). Similarly, Cypher stents have been superior to Endeavor stents regarding the primary end point of late luminal loss in the recent ENDEAVOR III trial. Meanwhile, the on-site rapamycin-coated stents (ISAR stents) had an equivalent antiproliferative efficacy to Taxus stents in the ISAR-TEST trial. However, none of these studies evaluated angiographic restenosis as their primary endpoint and no direct comparisons between the 3 DES -Cypher, Endeavor and ISAR stents, have been performed. The Cypher stent is a stainless steel stent coated with sirolimus with use of permanent polymers while the Endeavor stent is a cobalt alloy based stent coated with zotarolimus which also uses permanent polymers for drug-storage and release. The ISAR stent is a rough surface stainless steel stent that can be coated with sirolimus in the cath lab without requiring permanent polymeric coating.

Official Title
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Randomized Comparison of 3 Limus Agent-Eluting Stents for the Reduction of Coronary Restenosis

Conditions
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Coronary Disease

Intervention / Treatment
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* Device: Rapamycin-eluting Stent
* Device: Zotarolimus-eluting Stent
* Device: Rapamycin-eluting Stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients older than age 18 ´ presence of ischemic symptoms or evidence of myocardial ischemia in the presence of ≥50% de novo stenosis located in native coronary vessels written, informed consent by the patient or her/his legally-authorized representative for participation in the study. Exclusion Criteria: Target lesion located in the left main trunk or bypass graft In-stent restenosis Cardiogenic shock Malignancies or other comorbid conditions with life expectancy less than one year or that may result in protocol non-compliance Known allergy to the study medications: aspirin, clopidogrel, zotarolimus, sirolimus, stainless steel, or cobalt alloy Pregnancy (present, suspected or planned) or positive pregnancy test Previous enrollment in this trial Patient's inability to fully cooperate with the study protocol

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>Rapamycin-eluting Stent (Cypher) | Device: Rapamycin-eluting Stent<br>* due to randomization, Cypher stent will be implanted<br>* Other names: Cypher;|
| Active Comparator: B<br>Zotarolimus-eluting Stent (Endeavor) | Device: Zotarolimus-eluting Stent<br>* due to randomization, Endeavor stent will be implanted<br>* Other names: Endeavor;|
| Active Comparator: C<br>Rapamycin-eluting Stent | Device: Rapamycin-eluting Stent<br>* due to randomization, rapamycin-eluting stent will be implanted<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary end point of the study is the incidence of binary angiographic restenosis at 6-8 month follow-up angiography, measured by QCA in the in-segment area. |  | 6-8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The need of target lesion revascularization defined as any revascularization procedure involving the target lesion due to luminal re-narrowing in the presence of symptoms or objective signs of ischemia. |  | 9-12 months | 
| The combined incidence of death or myocardial infarction. |  | 9-12 months | 
| In-stent late luminal loss. |  | 9-12 months | 
| Incidence of stent thrombosis. |  | 9-12 months |