BES, EES, and ZES-R in Real World Practice

Study Overview
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Brief Summary
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The primary objective of this study is to compare the rate of device-oriented composite consisted of cardiac death, myocardial infarction not clearly attributable to a nontarget vessel, and clinically indicated target lesion revascularization among the patients treated with EES, ZES-R, or BES at 24-month clinical follow-up post-index procedure. Trial end points are summarized in Table I. The hypothesis is that BES is equivalent to EES or BES is equivalent to ZES-R at the primary end point.

Detailed Description
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Previous randomized trials have shown the superior efficacy of drug-eluting stents (DES), such as sirolimus-eluting stent (SES, CYPHER, Cordis, US), paclitaxel-eluting stent (PES, TAXUS, Boston Scientific, US), and zotarolimus-eluting stent (ZES, Endeavor, Medtronic, US) compared with bare metal stents (BMS) by reducing neointimal hyperplasia, late luminal loss, and angiographic restenosis leading to decreased target lesion revascularization. Unfortunately, restenosis still occurs and late stent thrombosis can develop by delaying endoluminal healing or by chronic inflammation.Accordingly, development of new DES is required to improve efficacy by reducing revascularization and safety by reducing the risk of stent thrombosis. With the improvement of polymer, drug, and the platform, the 2nd generation DES, including everolimus-eluting stent (EES, Xience V or Xience Prime, Abbott, USA), zotarolimus-eluting stent with biolinx polymer (ZES-R, Endeavor Resolute or Endeavor Resolute Integrity, Medtronic, USA), and biolimus-eluting stent (BES, BioMatrix or Biomatrix Flex, Biosensors, USA), have been shown to be superior or non-inferior in safety and efficacy trials compared with 1st generation DES. However, it is difficult to know if there are any differences in efficacy and safety between the EES, the ZES-R, and the BES, in real world practice due to the lack of data comparing these three 2nd generation DES directly. This study provides the evidence for the CHOICE of stent when physicians are treating patients by percutaneous coronary intervention.

Official Title
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A Multicenter, Open-labeled, Randomized Controlled Trial Comparing Three 2nd Generation Drug-Eluting Stents in Real-World Practice

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: Biolimus-eluting stent
* Device: Everolimus-eluting stent
* Device: Zotarolimus-eluting stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age > 19 years Subject is able to verbally confirm understanding of risks, benefits and treatment alternatives of receiving the drug-eluting stent(s) and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure Subject must have significant stenosis (>50% by visual estimate) on a native or in-stent coronary artery Subject must have evidence of myocardial ischemia (e.g., stable, unstable angina, recent infarction, acute myocardial infarction, positive functional study or a reversible changes in the ECG consistent with ischemia). In subjects with coronary artery stenosis >75%, evidence of myocardial ischemia does not have to be documented Exclusion Criteria Subject has a known hypersensitivity or contraindication to any of the following medications: heparin, aspirin, clopidogrel, prasugrel, ticagrelor, biolimus A9, everolimus, zotarolimus, stainless steel, cobalt chromium, contrast media (Patients with documented sensitivity to contrast media, which can be effectively premedicated with steroid and diphenhydramine may be enrolled. However, those with true anaphylaxis to prior contrast media should not be enrolled.) Subject in use of systemic (intravenous) biolimus A9, everolimus or zotarolimus within 12 months. Female subject of childbearing potential, unless a recent pregnancy test is negative, who possibly plans to become pregnant any time after enrollment into this study Subject planned an elective surgical procedure that would necessitate interruption of antiplatelet during the first 12 months post enrollment Subject with non-cardiac co-morbid condition with life expectancy < 2 year or that may result in protocol non-compliance (per site investigator's medical judgment) Subject with cardiogenic shock at presentation Subject who are actively participating in another drug or device investigational study, who have not completed the primary end point follow-up period

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
Interventional Model Description: BES EES ZES-R
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Biolimus-eluting stent<br>Biomatrix stent, Biosensors, USA Biomatrix Flex stent, Biosensors, USA | Device: Biolimus-eluting stent<br>* Biolimus-eluting stent (BES, BioMatrix or BioMatrix Flex, Biosensors, USA) has bio-degradable polymer which is consisted with poly-lactic acid (PLA) and degraded into H2O and CO2 while releasing the biolimus. BES would be expected to reduce the stent thrombosis comparing with the DES with durable polymer.<br>* Other names: Biomatrix flex, Biosensors, USA;|
| Active Comparator: Everolimus-eluting stent<br>Xience Prime stent, Abbott, USA Xience V stent, Abbott, USA | Device: Everolimus-eluting stent<br>* Everolimus-eluting stent (EES, Xience V or Xience Prime, Abbott, USA) use the MULTILINK VISION stent platform and durable polymer containing everolimus. It has the thinnest strut thickness among the available DES in Korea.<br>* Other names: Xience Prime, Abbott, USA;|
| Active Comparator: Zotarolimus-eluting stent<br>Endeavor resolute, Medtronic, USA Endeavor resolute integrity, Medtronic, USA | Device: Zotarolimus-eluting stent<br>* Zotarolimus-eluting stent with biolinx polymer (ZES, Endeavor Resolute or Endeavor Resolute Intergrity, Medtronic, USA) has DRIVER stent platform. The durable polymer in this DES has changed from phosphorylcholine (PC) polymer which was used in Endeavor to Biolinx polymer which has more biocompatible features.<br>* Other names: Endeavor Resolute Integrity, Medtronic, USA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device-oriented composite | Device-oriented composite consisted of cardiac death, myocardial infarction not clearly attributable to a nontarget vessel, and clinically indicated target lesion revascularization (TLR) at 24-month clinical follow-up | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-oriented composite | Patient-oriented composite consisted of all-cause mortality, any myocardial infarction, and any revascularization at 24-month clinical follow-up | at 24 months | 
| Device-oriented composite | Device-oriented composite at 12-month clinical follow-up | 12 months | 
| Patient-oriented composite | Patient-oriented composite at 12-month clinical follow-up | 12 months | 
| Each component of device- and patient-oriented composite | Each component of device- and patient-oriented composite at 12 months | 12 months | 
| Each component of device- and patient-oriented composite | Each component of device- and patient-oriented composite at 24 months | 24 months | 
| ARC defined stent thrombosis | ARC defined stent thrombosis at 12 months | 12 months | 
| ARC defined stent thrombosis | ARC defined stent thrombosis at 24 months | 24 months | 
| Stent thrombosis | ARC defined stent thrombosis at 12 months after randomization | 12 months | 
| Stent thrombosis | ARC defined stent thrombosis at 24 months after randomization | 24 months | 
| Bleeding complications defined by BARC definition | Bleeding complications defined by BARC definition before discharge | before discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary artery disease, Percutaneous coronary intervention, Drug-eluting stent