Triple Versus Dual Antiplatelet Therapy After ABT578-Eluting Stent (DECLARELONG)

Comparison of Triple Versus Dual Antiplatelet Therapy After ABT578-Eluting Stent Implantation For Long Coronary Lesions

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: cilostazol; Drug: placebo

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.

• Study Type: Interventional
• Enrollment (Anticipated): 486
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bucheon, Korea, Republic of
    • SoonChunHyang University Bucheon Hospital
  • Cheonan, Korea, Republic of
    • Soonchunhyang University Hospital, Cheonan
  • Chuncheon, Korea, Republic of
    • Kangwon National University Hospital
  • Daejeon, Korea, Republic of
    • Chungnam National University Hospital
  • PyeongChon, Korea, Republic of
    • Hallym University Sacred Heart Hospital,
  • Seoul, Korea, Republic of, 138-736
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • SoonChunHyang University Seoul Hospital
  • Seoul, Korea, Republic of
    • Hangang Sacred Heart Hospital
  • Seoul, Korea, Republic of
    • Seoul Veterans Hospital
  • Ulsan, Korea, Republic of
    • Ulsan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cilostazol; Cilostazol 200mg loading dose within 1 hours after successful stenting, followed by 100mg bid for 8 months	Drug: cilostazol; cilostazol 200mg loading dose within 1 hours after successful stenting, followed by 100mg bid for 8 months
Placebo Comparator: placebo; Control placebo 200mg loading dose within 1 hours after successful stenting, followed by 100mg bid for 8 months	Drug: placebo; placebo 200mg loading dose within 1 hours after successful stenting, followed by 100mg bid for 8 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Angiographic in-stent late loss	8-months after randomization

Secondary Outcome Measures

Outcome Measure	Time Frame
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	12 months

Collaborators and Investigators

• Sponsor: CardioVascular Research Foundation, Korea
• Collaborators: Otsuka Korea
• Investigators: Principal Investigator: Seung-Wook Park, MD,PhD, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: December 31, 2007
• First Submitted That Met QC Criteria: December 31, 2007
• First Posted (Estimate): January 10, 2008

Study Record Updates

• Last Update Posted (Estimate): March 18, 2010
• Last Update Submitted That Met QC Criteria: March 17, 2010
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: stents; cilostazol
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Neuroprotective Agents; Protective Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Cilostazol
• Other Study ID Numbers: 2007-0003