Rapamycin+Estradiol- vs. Rapamycin-Eluting Stents to Reduce Restenosis (ISAR-PEACE)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether adding estradiol to rapamycin better prevents coronary artery reblockage after drug-eluting 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 or absence of polymers employed for drug storage and modification of drug-release kinetics as well as type of polymer used for this purpose. 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, particularly after discontinuation of thienopyridine therapy, as well as of delayed onset of restenosis or catch-up phenomenon with DESs. Based on animal and human pathological data, investigators have linked the above-mentioned concerns to the presence of permanent polymers in DESs, which have a proinflammatory and prothrombogenic potential, and sometimes may induce a hypersensitivity reaction. On the other hand, lack of or delayed reendothelialization is considered an important factor for development of coronary reblockage. Estradiol has been shown to promote rapid reendothelialization of the stent and to reduce the restenosis after PCI. This trial will compare the anti-restenotic efficacy of the polymer-free rapamycin plus 17β estradiolvalerat -eluting stent with that of the polymer-free rapamycin-eluting stent in patients with coronary artery disease. The ISAR stent is a rough surface stainless steel stent which allows coating without the need of polymer (PF ISAR stent) in the cath lab.

Official Title
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Prospective, Randomized Trial of Rapamycin Plus Estradiol-Eluting Stents Versus Rapamycin-Eluting Stents For The Reduction of Coronary Restenosis (ISAR-PEACE)

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Device: rapamycin plus 17beta estradiolvalerat-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 with 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. Acute ST-elevation myocardial infarction. 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: aspirin, clopidogrel, rapamycin, estradiol, stainless steel. 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 |
| --- | --- |
| Experimental: 1<br>rapamycin plus 17beta estradiolvalerat-eluting stent | Device: rapamycin plus 17beta estradiolvalerat-eluting stent<br>* rapamycin plus 17beta estradiolvalerat-eluting stent was implanted due to randomisation<br>|
| Experimental: 2<br>rapamycin-eluting stent | Device: rapamycin-eluting stent<br>* rapamycin-eluting stent was implanted due to randomisation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| in-stent late luminal loss |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-segment binary angiographic restenosis |  | 1 year | 
| Need of target lesion revascularization |  | 1 year | 
| Combined incidence of death or myocardial infarction |  | 1 year | 
| Incidence of stent thrombosis. |  | 1 year |