Clinical trial NCT00589927: Triple Versus Dual Antiplatelet Therapy After ABT578-Eluting Stent
Official title: Comparison of Triple Versus Dual Antiplatelet Therapy After ABT578-Eluting Stent Implantation For Long Coronary Lesions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: stents
cilostazol
Lead sponsor: CardioVascular Research Foundation, Korea
Sponsor class: OTHER
Collaborators: name: Otsuka Korea
First posted: 2008-01-10
Enrollment: 486
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate whether the cilostazol reduce neointimal hyperplasia after ZES (Zotarolimus-eluting stents) implantation, the investigators performed double-blind,randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol) and dual antiplatelet therapy (aspirin plus clopidogrel) for 8 months in patients with long coronary lesion treated with ZES.

Detailed description: Use of drug-eluting stent (DES) has reduced the incidence of restenosis rate and the need for repeat revascularization compared to using bare metal stents. DES implantation also significantly reduced the angiographic restenosis in patients with long coronary lesions.However, although the use of DES has decreased the effect of lesion length on restenosis, the restenosis after DES implantation of long coronary lesions remain at a higher risk of restenosis.

Cilostazol, a phosphodiesterase III inhibitor, has been known to reduce smooth muscle proliferation and intimal hyperplasia after endothelial injury and restenosis after balloon angioplasty and bare-metal stent (BMS) implantation when compared with aspirin and clopidogrel or ticlopidine. Recently, the impact of 6-month cilostazol treatment in addition to aspirin and clopidogrel on neointimal hyperplasia after sirolimus-(SES) or paclitaxel-eluting stent (PES) implantation for long-coronary lesions has been evaluated in our institution. It reported that cilostazol treatment achieved primary end point (in-stent late loss) and reduced need of target lesion revascularization without significant adverse drug-side effects with open-label design, which suggest that 6-month treatment of cilostazol effectively inhibits the neointimal hyperplasia after DES implantation and can be safely applied to the patients or lesions with higher risk of restenosis such as diabetes and long lesions.However, our study was done in unblinded manner and might underestimate the angiographic results due to relatively short-term follow-up angiographic follow-up(6-month.

Recently commercially available new-DES, zotarolimus-eluting stent (ZES) demonstrated significant reduction of restenosis and cardiac events during 9-month. However, it has not been tested that 8-month treatment of cilostazol also effectively inhibits the neointimal hyperplasia after ZES implantation in patients with long coronary lesions. Therefore, to evaluate whether the cilostazol reduce neointimal hyperplasia after ZES implantation, the investigators performed double-blind, randomized, multicenter, prospective study compared triple antiplatelet therapy (aspirin plus clopidogrel plus cilostazol) and dual antiplatelet therapy (aspirin plus clopidogrel) for 8 months in patients with long coronary lesion treated with ZES.

Eligibility criteria: Inclusion Criteria:

1. Clinical 1) Patients with angina and documented ischemia or patients with documented silent ischemia 2) Patients who are eligible for intracoronary stenting 3) Age \>18 years, \<75 ages
2. Angiographic 1) De novo lesion 2) Percent diameter stenosis ≥50% 3) Reference vessel size \>2.5 mm by visual estimation 4) Lesion length \>25 mm by visual estimation that is required for long Endeavor stent implantation (planned total stent length \>30mm)

Exclusion Criteria:

1. History of bleeding diathesis or coagulopathy
2. Pregnant
3. Known hypersensitivity or contra-indication to contrast agent, heparin, sirolimus and paclitaxel
4. Limited life-expectancy (less than 1 year) due to combined serious disease
5. ST-elevation acute myocardial infarction
6. Characteristics of lesion 1) Left main disease 2) In-stent restenosis 3) Graft vessels
7. Hematological disease (Neutropenia \<3000/mm3, Thrombocytopenia \<100,000/mm3)
8. Hepatic dysfunction, liver enzyme (ALT and AST) elevation \>3 times normal
9. Renal dysfunction, creatinine \>2.0mg/dL
10. Contraindication to aspirin, clopidogrel or cilostazol
11. planned bifurcation stenting

Primary outcomes:
measure: Angiographic in-stent late loss
timeFrame: 8-months after randomization
Secondary outcomes:
measure: Composite of death, MI, and target lesion or vessel revascularization at 12 months, In-stent and in-stent restenosis at 8 months, In-segment late loss at 8 months Adverse side effects during treatment
timeFrame: 12 months
Other outcomes:
Locations:
city: Bucheon
country: Korea, Republic of
facility: Soonchunhyang University Bucheon Hospital
city: Cheonan
country: Korea, Republic of
facility: Soonchunhyang University Hospital, Cheonan
city: Chuncheon
country: Korea, Republic of
facility: Kangwon National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: PyeongChon
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital,
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Hangang Sacred Heart Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul Veterans Hospital
city: Seoul
country: Korea, Republic of
facility: Soonchunhyang University Seoul Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
Study officials:
affiliation: Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine
name: Seung-Wook Park, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee SW, Park SW, Kim YH, Yun SC, Park DW, Lee CW, Kang SJ, Park SJ, Lee JH, Choi SW, Seong IW, Lee NH, Cho YH, Shin WY, Lee SJ, Lee SW, Hyon MS, Bang DW, Choi YJ, Kim HS, Lee BK, Lee K, Park HK, Park CB, Lee SG, Kim MK, Park KH, Park WJ; DECLARE-LONG II Study Investigators. A randomized, double-blind, multicenter comparison study of triple antiplatelet therapy with dual antiplatelet therapy to reduce restenosis after drug-eluting stent implantation in long coronary lesions: results from the DECLARE-LONG II (Drug-Eluting Stenting Followed by Cilostazol Treatment Reduces Late Restenosis in Patients with Long Coronary Lesions) trial. J Am Coll Cardiol. 2011 Mar 15;57(11):1264-70. doi: 10.1016/j.jacc.2010.10.035.