BES, EES, and ZES-R in Real World Practice - Full Text View

Purpose

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.

Condition	Intervention	Phase
Coronary Artery Disease	Device: Biolimus-eluting stent Device: Everolimus-eluting stent Device: Zotarolimus-eluting stent	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:	A Multicenter, Open-labeled, Randomized Controlled Trial Comparing Three 2nd Generation Drug-Eluting Stents in Real-World Practice

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease

Drug Information available for: Sirolimus Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Yonsei University:

Primary Outcome Measures:

Device-oriented composite [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
Device-oriented composite consisted of cardiac death, myocardial infarction not clearly attributable to a nontarget vessel, and clinically indicated TLR at 24-month clinical follow-up

Secondary Outcome Measures:

Patient-oriented composite [ Time Frame: at 24 months ] [ Designated as safety issue: Yes ]
Patient-oriented composite consisted of all-cause mortality, any myocardial infarction, and any revascularization at 24-month clinical follow-up
Device-oriented composite [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Device-oriented composite at 12-month clinical follow-up
Patient-oriented composite [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Patient-oriented composite at 12-month clinical follow-up
Each component of device- and patient-oriented composite [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Each component of device- and patient-oriented composite at 12 months
Each component of device- and patient-oriented composite [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
Each component of device- and patient-oriented composite at 24 months
ARC defined stent thrombosis [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
ARC defined stent thrombosis at 12 months
ARC defined stent thrombosis [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
ARC defined stent thrombosis at 24 months
Stent thrombosis [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
ARC defined stent thrombosis at 12 months after randomization
Stent thrombosis [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
ARC defined stent thrombosis at 24 months after randomization
Bleeding complications defined by BARC definition [ Time Frame: before discharge ] [ Designated as safety issue: Yes ]
Bleeding complications defined by BARC definition before discharge

Estimated Enrollment:	2580
Study Start Date:	January 2013
Estimated Study Completion Date:	June 2016
Estimated Primary Completion Date:	June 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Biolimus-eluting stent Biomatrix stent, Biosensors, USA Biomatrix Flex stent, Biosensors, USA	Device: Biolimus-eluting stent Biolimus-eluting stent (BES, BioMatrixTM or BioMatrix FlexTM, Biosensors, USA) has bio-degradable polymer which is consisted with PLA (poly-lactic acid) 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. Other Names: Biomatrix, Biosensors, USA Biomatrix flex, Biosensors, USA
Active Comparator: Everolimus-eluting stent Xience Prime stent, Abbott, USA Xience V stent, Abbott, USA	Device: Everolimus-eluting stent Everolimus-eluting stent (EES, Xience VTM or Xience PrimeTM, 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. Other Names: Xience V, Abbott, USA Xience Prime, Abbott, USA
Active Comparator: Zotarolimus-eluting stent Endeavor resolute, Medtronic, USA Endeavor resolute integrity, Medtronic, USA	Device: Zotarolimus-eluting stent Zotarolimus-eluting stent with biolinx polymer (ZES, Endeavor ResoluteTM or Endeavor Resolute IntergrityTM, Medtronic, USA) has DRIVER stent platform. The durable polymer in this DES has changed from PC polymer which was used in EndeavorTM to Biolinx polymer which has more biocompatible features. Other Names: Endeavor Resolute, Medtronic, USA Endeavor Resolute Intergrity, Medtronic, USA

Detailed Description:

Previous randomized trials have shown the superior efficacy of drug-eluting stents (DES), such as sirolimus-eluting stent (SES, CYPHERTM, Cordis, US), paclitaxel-eluting stent (PES, TAXUSTM, Boston Scientific, US), and zotarolimus-eluting stent (ZES, EndeavorTM, 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 VTM or Xience PrimeTM, Abbott, USA), zotarolimus-eluting stent with biolinx polymer (ZES-R, Endeavor ResoluteTM or Endeavor Resolute IntegrityTM, Medtronic, USA), and biolimus-eluting stent (BES, BioMatrixTM or Biomatrix FlexTM, 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.

Eligibility

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

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01397175

Contacts

Contact: Junghan Yoon, M.D., Ph.D.	82-33-741-0906	jyoon@yonsei.ac.kr
Contact: Young Jin Youn, M.D.	82-33-741-1216	younyj@yonsei.ac.kr

Locations

Korea, Republic of
Wonju Christian Hospital	Recruiting
Wonju, Gangwon, Korea, Republic of, 220-701
Contact: Junghan Yoon, M.D., Ph.D. 82-33-741-0906 jyoon@yonsei.ac.kr
Contact: Young Jin Youn, M.D. 82-33-741-1216 younyj@yonsei.ac.kr
Chonnam National University Hospital	Recruiting
Chuncheon, Korea, Republic of
Contact: Myung Ho Jeong, MD, PhD myungho@chollian.net
Daegu Catholic University Hospital	Recruiting
Daegu, Korea, Republic of
Contact: Jin-Bae Lee, MD, PhD jblee@cu.ac.kr
Inha University Hospital	Recruiting
Incheon, Korea, Republic of
Contact: Keum Soo Park, MD, PhD kspark@inha.ac.kr
Suncheon St. Carollo Hospital	Recruiting
Suncheon, Korea, Republic of
Contact: Jang Hyun Cho, MD, PhD goodnew8@naver.com

Sponsors and Collaborators

Yonsei University

Gangwon Cardiovascular Health Research Institute

Investigators

Principal Investigator:

Junghan Yoon, M.D., Ph.D.

Wonju Chrisitian Hospital

More Information

Publications:

Kastrati A, Dibra A, Mehilli J, Mayer S, Pinieck S, Pache J, Dirschinger J, Schömig A. Predictive factors of restenosis after coronary implantation of sirolimus- or paclitaxel-eluting stents. Circulation. 2006 May 16;113(19):2293-300. Epub 2006 May 8.

Moses JW, Leon MB, Popma JJ, Fitzgerald PJ, Holmes DR, O'Shaughnessy C, Caputo RP, Kereiakes DJ, Williams DO, Teirstein PS, Jaeger JL, Kuntz RE; SIRIUS Investigators. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med. 2003 Oct 2;349(14):1315-23.

Pfisterer M, Brunner-La Rocca HP, Buser PT, Rickenbacher P, Hunziker P, Mueller C, Jeger R, Bader F, Osswald S, Kaiser C; BASKET-LATE Investigators. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol. 2006 Dec 19;48(12):2584-91. Epub 2006 Nov 2.

Stone GW, Ellis SG, Cox DA, Hermiller J, O'Shaughnessy C, Mann JT, Turco M, Caputo R, Bergin P, Greenberg J, Popma JJ, Russell ME; TAXUS-IV Investigators. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med. 2004 Jan 15;350(3):221-31.

Holmes DR Jr, Kereiakes DJ, Laskey WK, Colombo A, Ellis SG, Henry TD, Popma JJ, Serruys PW, Kimura T, Williams DO, Windecker S, Krucoff MW. Thrombosis and drug-eluting stents: an objective appraisal. J Am Coll Cardiol. 2007 Jul 10;50(2):109-18. Epub 2007 May 22. Review.

Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005 May 4;293(17):2126-30.

Cutlip DE, Baim DS, Ho KK, Popma JJ, Lansky AJ, Cohen DJ, Carrozza JP Jr, Chauhan MS, Rodriguez O, Kuntz RE. Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials. Circulation. 2001 Apr 17;103(15):1967-71.

Doyle B, Rihal CS, O'Sullivan CJ, Lennon RJ, Wiste HJ, Bell M, Bresnahan J, Holmes DR Jr. Outcomes of stent thrombosis and restenosis during extended follow-up of patients treated with bare-metal coronary stents. Circulation. 2007 Nov 20;116(21):2391-8. Epub 2007 Nov 5.

Daemen J, Wenaweser P, Tsuchida K, Abrecht L, Vaina S, Morger C, Kukreja N, Jüni P, Sianos G, Hellige G, van Domburg RT, Hess OM, Boersma E, Meier B, Windecker S, Serruys PW. Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet. 2007 Feb 24;369(9562):667-78.

Roukoz H, Bavry AA, Sarkees ML, Mood GR, Kumbhani DJ, Rabbat MG, Bhatt DL. Comprehensive meta-analysis on drug-eluting stents versus bare-metal stents during extended follow-up. Am J Med. 2009 Jun;122(6):581.e1-10. doi: 10.1016/j.amjmed.2008.12.019.

Kirtane AJ, Gupta A, Iyengar S, Moses JW, Leon MB, Applegate R, Brodie B, Hannan E, Harjai K, Jensen LO, Park SJ, Perry R, Racz M, Saia F, Tu JV, Waksman R, Lansky AJ, Mehran R, Stone GW. Safety and efficacy of drug-eluting and bare metal stents: comprehensive meta-analysis of randomized trials and observational studies. Circulation. 2009 Jun 30;119(25):3198-206. doi: 10.1161/CIRCULATIONAHA.108.826479. Epub 2009 Jun 15.

Mauri L, Hsieh WH, Massaro JM, Ho KK, D'Agostino R, Cutlip DE. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med. 2007 Mar 8;356(10):1020-9. Epub 2007 Feb 12.

Stone GW, Moses JW, Ellis SG, Schofer J, Dawkins KD, Morice MC, Colombo A, Schampaert E, Grube E, Kirtane AJ, Cutlip DE, Fahy M, Pocock SJ, Mehran R, Leon MB. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007 Mar 8;356(10):998-1008. Epub 2007 Feb 12.

Caixeta A, Lansky AJ, Serruys PW, Hermiller JB, Ruygrok P, Onuma Y, Gordon P, Yaqub M, Miquel-Hebert K, Veldhof S, Sood P, Su X, Jonnavithula L, Sudhir K, Stone GW; SPIRIT II and III Investigators. Clinical follow-up 3 years after everolimus- and paclitaxel-eluting stents: a pooled analysis from the SPIRIT II (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With De Novo Native Coronary Artery Lesions) and SPIRIT III (A Clinical Evaluation of the Investigational Device XIENCE V Everolimus Eluting Coronary Stent System [EECSS] in the Treatment of Subjects With De Novo Native Coronary Artery Lesions) randomized trials. JACC Cardiovasc Interv. 2010 Dec;3(12):1220-8.

Kedhi E, Joesoef KS, McFadden E, Wassing J, van Mieghem C, Goedhart D, Smits PC. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial. Lancet. 2010 Jan 16;375(9710):201-9. Epub 2010 Jan 7.

Stone GW, Midei M, Newman W, Sanz M, Hermiller JB, Williams J, Farhat N, Mahaffey KW, Cutlip DE, Fitzgerald PJ, Sood P, Su X, Lansky AJ; SPIRIT III Investigators. Comparison of an everolimus-eluting stent and a paclitaxel-eluting stent in patients with coronary artery disease: a randomized trial. JAMA. 2008 Apr 23;299(16):1903-13.

Stone GW, Rizvi A, Sudhir K, Newman W, Applegate RJ, Cannon LA, Maddux JT, Cutlip DE, Simonton CA, Sood P, Kereiakes DJ; SPIRIT IV Investigators. Randomized comparison of everolimus- and paclitaxel-eluting stents. 2-year follow-up from the SPIRIT (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) IV trial. J Am Coll Cardiol. 2011 Jun 28;58(1):19-25. Epub 2011 Apr 21.

Serruys PW, Silber S, Garg S, van Geuns RJ, Richardt G, Buszman PE, Kelbaek H, van Boven AJ, Hofma SH, Linke A, Klauss V, Wijns W, Macaya C, Garot P, DiMario C, Manoharan G, Kornowski R, Ischinger T, Bartorelli A, Ronden J, Bressers M, Gobbens P, Negoita M, van Leeuwen F, Windecker S. Comparison of zotarolimus-eluting and everolimus-eluting coronary stents. N Engl J Med. 2010 Jul 8;363(2):136-46. Epub 2010 Jun 16.

Silber S, Windecker S, Vranckx P, Serruys PW; RESOLUTE All Comers investigators. Unrestricted randomised use of two new generation drug-eluting coronary stents: 2-year patient-related versus stent-related outcomes from the RESOLUTE All Comers trial. Lancet. 2011 Apr 9;377(9773):1241-7. Epub 2011 Apr 1.

Stefanini GG, Kalesan B, Serruys PW, Heg D, Buszman P, Linke A, Ischinger T, Klauss V, Eberli F, Wijns W, Morice MC, Di Mario C, Corti R, Antoni D, Sohn HY, Eerdmans P, van Es GA, Meier B, Windecker S, Jüni P. Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial. Lancet. 2011 Dec 3;378(9807):1940-8. Epub 2011 Nov 8.

Windecker S, Serruys PW, Wandel S, Buszman P, Trznadel S, Linke A, Lenk K, Ischinger T, Klauss V, Eberli F, Corti R, Wijns W, Morice MC, di Mario C, Davies S, van Geuns RJ, Eerdmans P, van Es GA, Meier B, Jüni P. Biolimus-eluting stent with biodegradable polymer versus sirolimus-eluting stent with durable polymer for coronary revascularisation (LEADERS): a randomised non-inferiority trial. Lancet. 2008 Sep 27;372(9644):1163-73. Epub 2008 Aug 31.

Lüscher TF, Steffel J, Eberli FR, Joner M, Nakazawa G, Tanner FC, Virmani R. Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications. Circulation. 2007 Feb 27;115(8):1051-8. Review.

Responsible Party:	Yoon Junghan, Professor of Cardiology, Department of Internal Medicine, Yonsei University
ClinicalTrials.gov Identifier:	NCT01397175 History of Changes
Other Study ID Numbers:	CHOICE
Study First Received:	July 5, 2011
Last Updated:	March 1, 2013
Health Authority:	Korea: Institutional Review Board

Keywords provided by Yonsei University:

Coronary artery disease
Percutaneous coronary intervention
Drug-eluting stent

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Everolimus
Sirolimus

Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on May 23, 2013

BES, EES, and ZES-R in Real World Practice (CHOICE)