Clinical trial NCT00698607: Efficacy of Xience/Promus Versus Cypher in rEducing Late Loss After stENTing
Official title: Comparison of the Efficacy of Everolimus-Eluting Versus Sirolimus-Eluting Stent for Coronary Lesions
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Everolimus
Sirolimus
drug eluting stent
Clopidogrel
Lead sponsor: Seoul National University Hospital
Sponsor class: OTHER
Collaborators: name: Abbott
name: Boston Scientific Corporation
First posted: 2008-06-17
Enrollment: 1466
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: In-segment late luminal loss (LL) at 9 months for comparison of stenting with EECSS vs. SECSS.
timeFrame: 9 months
measure: 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
timeFrame: 12 months
Secondary outcomes:
measure: All death
timeFrame: 5 years
measure: Cardiac death
timeFrame: 5 Years
measure: Myocardial infarction
timeFrame: 5 years
measure: Target vessel revascularization (TVR) (all and ischemia-driven)
timeFrame: 5 years
measure: Target lesion revascularization (TLR) (all and ischemia-driven)
timeFrame: 5 years
measure: Stent thrombosis
timeFrame: 5 years
measure: Acute success (device, lesion, and procedure)
timeFrame: Index procedure
measure: Bleeding
timeFrame: 5 years
measure: Cerebrovascular accident
timeFrame: 5 years
measure: In-stent LL at 9 months
timeFrame: 9 months
measure: Angiographic pattern of restenosis at 9-month angiographic follow-up
timeFrame: 9 months
measure: In-stent and in-segment % diameter stenosis (%DS) at 9 months
timeFrame: 9 months
measure: In-stent % volume obstruction (%VO) at 9 months
timeFrame: 9 months
measure: Incomplete stent apposition post index procedure
timeFrame: Index procedure
measure: Persisting incomplete stent apposition, late-acquired incomplete stent apposition, aneurysm, thrombosis, and persisting dissection at 9 months
timeFrame: 9 months
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: 28 Yongon Dong, Jongro Gu
Study officials:
affiliation: Seoul National University Hospital
name: Hyo-Soo Kim, MD, PhD
role: STUDY_CHAIR
affiliation: Yonsei University
name: Yangsoo Jang, MD, PhD
role: STUDY_CHAIR
affiliation: Yonsei Univercity Wonju hospital
name: Jung-Han Yoon, MD, PhD
role: STUDY_CHAIR
affiliation: Gachon Kil Medical Center
name: Ahn Tae-Hoon, MD, PhD
role: STUDY_CHAIR
affiliation: Samsung Medical Center
name: Hyun-Cheol Kwon, MD, PhD
role: STUDY_CHAIR
affiliation: Seoul National University Bundang Hospital
name: In-Ho Chae, MD, PhD
role: STUDY_CHAIR
affiliation: Hallym University Medical Center
name: Young-Jin Choi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kandong Sacred heart Hospital
name: Kyoo-Rok Han, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ewha Women's University Hospital
name: Si-Hoon Park, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Chonnam National University Hospital
name: Myeong-Ho Chung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yonsei University
name: Hyuk-Moon Kwon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Health Insurance Service Ilsan Hospital
name: Dong-Woon Chun, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inje University Sanggye Hospital
name: Byung-Ok Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Korea University Anam Hospital
name: Do-Sun Lim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pusan National University Hospital
name: Taek-Jong Hong, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Borame Hospital
name: Woo-Young Chung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hallym University Kangnam Sacred Heart Hospital
name: Jae-Hun Chung, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.