Efficacy of Xience/Promus Versus Cypher in rEducing Late Loss After stENTing (EXCELLENT)

• ClinicalTrials.gov Identifier: NCT00698607
• Recruitment Status: Unknown
• First Posted: June 17, 2008
• Last Update Posted: June 29, 2010
• Sponsor: Seoul National University Hospital
• Collaborators: Abbott; Boston Scientific Corporation
• Information provided by: Seoul National University Hospital

Study Description

Brief Summary:

Objectives

1. To evaluate the safety and long-term effectiveness of coronary stenting with the Everolimus-eluting coronary stent system(EECSS) (XIENCETM V, Abbott Vascular, Santa Clara, CA, PromusTM, Boston Scientific, Natick, MA), compared with the sirolimus-eluting coronary stent system(SECSS) (CypherTM, Cordis Johnson & Johnson, Warren, NJ) in the treatment of coronary stenosis.
2. To evaluate the safety and efficacy of 6-month clopidogrel therapy compared with 12-month clopidogrel therapy.

Study Design: Prospective, open label, two-arm, randomized multi-center trial to test the non-inferiority of EECSS compared with the SECSS, and to test the non-inferiority of 6 months duration compared with 12 months duration of clopidogrel therapy. Patients will be randomized in a two by two factorial manner according to the type of drug eluting stent (EECSS vs. SECSS) and the duration of dual anti-platelet therapy (6 months vs. 12 months). Randomization will also be stratified per hospital for the presence of DM and the presence of long lesions (lesion length ≥ 28mm)

Patient Enrollment: 1,372 patients enrolled at 17 centers in Korea.

Patient Follow-Up: Clinical follow-up will occur at 1, 3, and 9 months, and at 1, 2, 3, 4, and 5 years. Investigator or designee may conduct follow-up as telephone contacts or office visits.

Primary Endpoint

• In-segment late luminal loss (LL) at 9 months for comparison of stenting with EECSS vs. SECSS.
• Target vessel failure (TVF) (cardiac death, myocardial infarction, ischemia driven target vessel revascularization) at 12 months for comparison of 6 months vs. 12 months of clopidogrel therapy

Secondary Endpoint

• All Death
• Cardiac death
• Myocardial infarction
• Target vessel revascularization (TVR) (all and ischemia-driven)
• Target lesion revascularization (TLR) (all and ischemia-driven)
• Stent thrombosis
• Acute success (device, lesion, and procedure)
• Bleeding
• Cerebrovascular accident
• In-stent LL at 9 months
• Angiographic pattern of restenosis at 9-month angiographic follow-up
• In-stent and in-segment % diameter stenosis (%DS) at 9 months
• In-stent % volume obstruction (%VO) at 9 months
• Incomplete stent apposition post index procedure
• Persisting incomplete stent apposition, late-acquired incomplete stent apposition, aneurysm, thrombosis, and persisting dissection at 9 months

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Device: Everolimus-eluting stent (Xience or Promus); Device: Sirolimus-eluting stent (Cypher); Drug: 6-month clopidogrel therapy; Drug: 12-month clopidogrel therapy	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 1466 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Comparison of the Efficacy of Everolimus-Eluting Versus Sirolimus-Eluting Stent for Coronary Lesions
• Study Start Date: June 2008
• Estimated Primary Completion Date: April 2010
• Estimated Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: E6; Everolimus-eluting stent 6-month clopidogrel therapy	Device: Everolimus-eluting stent (Xience or Promus); Use everolimus-eluting stent in the treatment of coronary stenosis; Other Names: Xience; Promus; Drug: 6-month clopidogrel therapy; Use clopidogrel for 6 months; Other Name: Plavix
Active Comparator: S6; Sirolimus-eluting stent 6-month clopidogrel therapy	Device: Sirolimus-eluting stent (Cypher); Use sirolimus-eluting stent in the treatment of coronary stenosis; Other Name: Cypher; Drug: 6-month clopidogrel therapy; Use clopidogrel for 6 months; Other Name: Plavix
Experimental: E12; Everolimus-eluting stent 12-month clopidogrel therapy	Device: Everolimus-eluting stent (Xience or Promus); Use everolimus-eluting stent in the treatment of coronary stenosis; Other Names: Xience; Promus; Drug: 12-month clopidogrel therapy; Use clopidogrel for 12 months; Other Name: Plavix
Active Comparator: S12; Sirolimus-eluting stent 12-month clopidogrel therapy	Device: Sirolimus-eluting stent (Cypher); Use sirolimus-eluting stent in the treatment of coronary stenosis; Other Name: Cypher; Drug: 12-month clopidogrel therapy; Use clopidogrel for 12 months; Other Name: Plavix

Outcome Measures

Primary Outcome Measures :

1. In-segment late luminal loss (LL) at 9 months for comparison of stenting with EECSS vs. SECSS. [ Time Frame: 9 months ]
2. Target vessel failure (TVF) (cardiac death, myocardial infarction, ischemia driven target vessel revascularization) at 12 months for comparison of 6 months vs. 12 months of clopidogrel therapy [ Time Frame: 12 months ]

Secondary Outcome Measures :

1. All death [ Time Frame: 5 years ]
2. Cardiac death [ Time Frame: 5 Years ]
3. Myocardial infarction [ Time Frame: 5 years ]
4. Target vessel revascularization (TVR) (all and ischemia-driven) [ Time Frame: 5 years ]
5. Target lesion revascularization (TLR) (all and ischemia-driven) [ Time Frame: 5 years ]
6. Stent thrombosis [ Time Frame: 5 years ]
7. Acute success (device, lesion, and procedure) [ Time Frame: Index procedure ]
8. Bleeding [ Time Frame: 5 years ]
9. Cerebrovascular accident [ Time Frame: 5 years ]
10. In-stent LL at 9 months [ Time Frame: 9 months ]
11. Angiographic pattern of restenosis at 9-month angiographic follow-up [ Time Frame: 9 months ]
12. In-stent and in-segment % diameter stenosis (%DS) at 9 months [ Time Frame: 9 months ]
13. In-stent % volume obstruction (%VO) at 9 months [ Time Frame: 9 months ]
14. Incomplete stent apposition post index procedure [ Time Frame: Index procedure ]
15. Persisting incomplete stent apposition, late-acquired incomplete stent apposition, aneurysm, thrombosis, and persisting dissection at 9 months [ Time Frame: 9 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

General Inclusion Criteria:

1. Subject must be at least 18 years of age.
2. Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving the XIENCE V EECS and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure.
3. Subject must have significant coronary artery stenosis (>50% by visual estimate)
4. Subject must have evidence of myocardial ischemia (e.g., stable, unstable angina, recent infarction, silent ischemia, positive functional study or a reversible changes in the electrocardiogram (ECG) consistent with ischemia. In subjects with coronary artery stenosis > 75%, evidence of myocardial ischemia does not have to be documented.
5. Subjects must be an acceptable candidate for Coronary Artery Bypass Graft (CABG) surgery.

Angiographically Inclusion Criteria

1. Target lesion(s) must be located in a native coronary artery with visually estimated diameter of ≥ 2.25 mm and ≤ 4.25 mm.
2. Target lesion(s) must be amenable for percutaneous coronary intervention

General Exclusion Criteria:

1. The patient has a known hypersensitivity or contraindication to any of the following medications (heparin, aspirin, clopidogrel, sirolimus, everolimus, Contrast media
2. Systemic (intravenous) Sirolimus, everolimus use within 12 months.
3. Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study.
4. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions.
5. Gastrointestinal or genitourinary bleeding within the prior 3 months, or major surgery within 2 months.
6. Current known current platelet count <100,000 cells/mm3 or Hgb <10 g/dL.
7. An elective surgical procedure is planned that would necessitate interruption of clopidogrel during the first 12 months post enrollment.
8. Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment).
9. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.
10. Patients who have received any stent implantation in the target vessel prior to enrollment.
11. Patients with LVEF<25% or those with cardiogenic shock
12. Patients with myocardial infarction within 72 hours
13. Creatinine level ≥ 3.0mg/dL or dependence on dialysis.
14. Severe hepatic dysfunction (AST and ALT: 3 times upper normal reference values).

Angiographic Exclusion Criteria

1. Patients with significant left main coronary artery stenosis
2. Patients who's target lesion has in-stent restenosis at the stented segment of drug-eluting stents or bare metal stents
3. Target lesions with chronic total occlusion
4. True bifurcation lesions requiring two stents

Contacts and Locations

Locations

Korea, Republic of

Seoul National University Hospital

Seoul, 28 Yongon Dong, Jongro Gu, Korea, Republic of, 110-744

Sponsors and Collaborators

Seoul National University Hospital

Abbott

Boston Scientific Corporation

Investigators

• Study Chair: Hyo-Soo Kim, MD, PhD; Seoul National University Hospital
• Study Chair: Yangsoo Jang, MD, PhD; Yonsei University
• Study Chair: Jung-Han Yoon, MD, PhD; Yonsei Univercity Wonju hospital
• Study Chair: Ahn Tae-Hoon, MD, PhD; Gachon Kil Medical Center
• Study Chair: Hyun-Cheol Kwon, MD, PhD; Samsung Medical Center
• Study Chair: In-Ho Chae, MD, PhD; Seoul National University Bundang Hospital
• Principal Investigator: Young-Jin Choi, MD, PhD; Hallym University Medical Center
• Principal Investigator: Kyoo-Rok Han, MD, PhD; Kandong Sacred heart Hospital
• Principal Investigator: Si-Hoon Park, MD, PhD; Ewha Women's University Hospital
• Principal Investigator: Myeong-Ho Chung, MD, PhD; Chonnam National University Hospital
• Principal Investigator: Hyuk-Moon Kwon, MD, PhD; Yonsei University
• Principal Investigator: Dong-Woon Chun, MD, PhD; National Health Insurance Service Ilsan Hospital
• Principal Investigator: Byung-Ok Kim, MD, PhD; Inje University Sanggye Hospital
• Principal Investigator: Do-Sun Lim, MD, PhD; Korea University Anam Hospital
• Principal Investigator: Taek-Jong Hong, MD, PhD; Pusan National University Hospital
• Principal Investigator: Woo-Young Chung, MD, PhD; Borame Hospital
• Principal Investigator: Jae-Hun Chung, MD, PhD; Hallym University Kangnam Sacred Heart Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jang JY, Jung HW, Lee BK, Shin DH, Kim JS, Hong SJ, Ahn CM, Kim BK, Ko YG, Choi D, Hong MK, Park KW, Gwon HC, Kim HS, Kwon HM, Jang Y. Impact of PRECISE-DAPT and DAPT Scores on Dual Antiplatelet Therapy Duration After 2nd Generation Drug-Eluting Stent Implantation. Cardiovasc Drugs Ther. 2021 Apr;35(2):343-352. doi: 10.1007/s10557-020-07008-7.

Kang J, Han JK, Kang DY, Zheng C, Yang HM, Park KW, Kang HJ, Koo BK, Kim HS. SYNTAX Score and SYNTAX Score II Can Predict the Clinical Outcomes of Patients with Left Main and/or 3-Vessel Disease Undergoing Percutaneous Coronary Intervention in the Contemporary Cobalt-Chromium Everolimus-Eluting Stent Era. Korean Circ J. 2020 Jan;50(1):22-34. doi: 10.4070/kcj.2019.0097. Epub 2019 Sep 30.

Jang JY, Shin DH, Kim JS, Hong SJ, Ahn CM, Kim BK, Ko YG, Choi D, Hong MK, Park KW, Gwon HC, Kim HS, Jang Y. Optimal duration of DAPT after second-generation drug-eluting stent in acute coronary syndrome. PLoS One. 2018 Nov 26;13(11):e0207386. doi: 10.1371/journal.pone.0207386. eCollection 2018.

Ko YG, Shin DH, Kim JS, Kim BK, Choi D, Hong MK, Gwon HC, Ahn T, Chae IH, Yoon JH, Kim HS, Jang Y; EXCELLENT investigators. Comparison of neointimal hyperplasia and peri-stent vascular remodeling after implantation of everolimus-eluting versus sirolimus-eluting stents: intravascular ultrasound results from the EXCELLENT study. Int J Cardiovasc Imaging. 2013 Aug;29(6):1229-36. doi: 10.1007/s10554-013-0199-5. Epub 2013 Mar 3.

Gwon HC, Hahn JY, Park KW, Song YB, Chae IH, Lim DS, Han KR, Choi JH, Choi SH, Kang HJ, Koo BK, Ahn T, Yoon JH, Jeong MH, Hong TJ, Chung WY, Choi YJ, Hur SH, Kwon HM, Jeon DW, Kim BO, Park SH, Lee NH, Jeon HK, Jang Y, Kim HS. Six-month versus 12-month dual antiplatelet therapy after implantation of drug-eluting stents: the Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting (EXCELLENT) randomized, multicenter study. Circulation. 2012 Jan 24;125(3):505-13. doi: 10.1161/CIRCULATIONAHA.111.059022. Epub 2011 Dec 16.

Park KW, Chae IH, Lim DS, Han KR, Yang HM, Lee HY, Kang HJ, Koo BK, Ahn T, Yoon JH, Jeong MH, Hong TJ, Chung WY, Jo SH, Choi YJ, Hur SH, Kwon HM, Jeon DW, Kim BO, Park SH, Lee NH, Jeon HK, Gwon HC, Jang YS, Kim HS. Everolimus-eluting versus sirolimus-eluting stents in patients undergoing percutaneous coronary intervention: the EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) randomized trial. J Am Coll Cardiol. 2011 Oct 25;58(18):1844-54. doi: 10.1016/j.jacc.2011.07.031.

Park KW, Yoon JH, Kim JS, Hahn JY, Cho YS, Chae IH, Gwon HC, Ahn T, Oh BH, Park JE, Shim WH, Shin EK, Jang YS, Kim HS. Efficacy of Xience/promus versus Cypher in rEducing Late Loss after stENTing (EXCELLENT) trial: study design and rationale of a Korean multicenter prospective randomized trial. Am Heart J. 2009 May;157(5):811-817.e1. doi: 10.1016/j.ahj.2009.02.008.

• Responsible Party: Hyo-Soo, Kim, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT00698607
• Other Study ID Numbers: EXCELLENT
• First Posted: June 17, 2008
• Last Update Posted: June 29, 2010
• Last Verified: June 2010

Keywords provided by Seoul National University Hospital:

Everolimus; Sirolimus; drug eluting stent; Clopidogrel

Additional relevant MeSH terms:

Coronary Artery Disease; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Sirolimus; Everolimus; Clopidogrel; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antifungal Agents