A New Strategy Regarding Discontinuation of Dual Antiplatelet

• ClinicalTrials.gov Identifier: NCT01145079
• Recruitment Status: Completed
• First Posted: June 16, 2010
• Last Update Posted: March 6, 2013
• Sponsor: Yonsei University
• Information provided by (Responsible Party): Yonsei University

Study Description

Brief Summary:

Drug-eluting stents (DES), markedly reducing the neointimal hyperplasia after stent implantation compared with bare-metal stents (BMS), have improved angiographic and clinical outcomes in the complex lesions and patients with high risks. However, currently, the fatal events related with stent thrombosis still occur and are the major limitation of the use of DES. Especially, late or very late thrombosis after DES implantation is an uncommon but life-threatening fatal complication presented with sudden death or myocardial infarction (MI) causing heart failure. The most powerful predictor for stent thrombosis is the discontinuation of clopidogrel. In consideration of current data regarding stent thrombosis and clinical situation of discontinuation of antiplatelet, zotarolimus-eluting stent (ZES) [Endeavor®, Medtronic Vascular, Santa Rosa, CA] might be anticipated to be safer than other DES during the long-term follow-up owing to healthy endothelialization. Endeavor® stent was consists of zotarolimus, thin-strut, cobalt-chromium alloy stent platform (DriverTM stent; Medtronic Vascular, Santa Rosa, CA), and phosphorylcholine coating. The ENDEAVOR II study demonstrated clinically and statistically significant improvement in all of study endpoints, including a 47 percent reduction in the primary endpoint of target vessel failure (TVF). In addition, the ENDEAVOR II trial showed a 0.5 percent rate of stent thrombosis at 30 days - with no late thrombosis beyond 30 days and no late stent malapposition. Because reendothelialization after ZES implantation may occur within 3 months, 3-month dual antiplatelet therapy is recommended in many clinical trials and real world practice. Shorter maintenance of dual antiplatelet therapy might minimize the risk for stent thrombosis in cases of discontinuation of antiplatelet and prevent waste medications and bleeding complications related with dual antiplatelet therapy. However, there have been no non-inferior or superior data of ZES considering all these circumstances. Therefore, the investigators hypothesize that ZES with 3-month dual antiplatelet therapy may be safe and beneficial in patients with coronary artery disease during follow-up than other DES, in spite of higher late lumen loss. To test this hypothesis, the investigators will perform a multi-center, randomized, prospective trial aimed at demonstrating the efficacy of the ZES versus other DES in patients with coronary artery disease in real world practice.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Disease	Device: Zotarolimus-eluting stent; Device: Zotarolimus-eluting stent for ACS and DM; Device: Everolimus-eluting stent for long lesion; Device: Sirolimus-eluting stent for short lesion	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 982 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A New Strategy Regarding Discontinuation of Dual Antiplatelet; Real Safety and Efficacy of a 3-month Dual Antiplatelet Therapy Following Zotarolimus-eluting Stents Implantation (RESET Trial)
• Study Start Date: May 2009
• Actual Primary Completion Date: January 2012
• Actual Study Completion Date: January 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Endeavor arm	Device: Zotarolimus-eluting stent; Zotarolimus-eluting stent
Active Comparator: Endeavor resolute arm	Device: Zotarolimus-eluting stent for ACS and DM; Zotarolimus-eluting stent for ACS and DM
Active Comparator: Xience arm	Device: Everolimus-eluting stent for long lesion; Everolimus-eluting stent for long lesion
Active Comparator: Cypher arm	Device: Sirolimus-eluting stent for short lesion; Sirolimus-eluting stent for short lesion

Outcome Measures

Primary Outcome Measures :

1. Primary Outcome The composite of cardio-vascular death, MI, stent thrombosis, TVR and bleeding (minor or major) following randomly assigned DES implantation [ Time Frame: 12 months after stent implantation ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Coronary artery disease including stable angina, unstable angina, acute non-ST elevation myocardial infarction and acute ST elevation myocardial infarction
• Age 20 years of older
• Patients with typical chest pain or evidences of myocardial ischemia (e.g., stable, unstable angina, silent ischemia and positive functional study or reversible changes in the electrocardiogram (ECG) consistent with ischemia
• Patients with signed informed consent
• Lesion and stent length for ACS and DM subgroup : Length of single lesion < 24 mm and, Summation of total length of all inserted DES in 3 vessel < 60 mm
• Lesion and stent length for ACS and DM subgroup : Length of single lesion < 24 mm and, Summation of total length of all inserted DES in 3 vessel < 60 mm
• Lesion and stent length for long lesion subgroup : Length of single stent per single lesion > 28 mm and, Summation of total length of all inserted DES in 3 vessel ≤ 90 mm, Possible overlapping stent
• Lesion and stent length for short lesion subgroup : Length of single lesion < 24 mm and, Summation of total length of all inserted DES in 3 vessel < 60 mm
• Significant coronary artery stenosis (>50% by visual estimate) considered for coronary revascularization with stent implantation
• Reference vessel diameter of 2.5 to 4.0 mm by operator assessment
• Lesion success (30% or less residual stenosis by visual assessment over the entire stent length, with TIMI-3 flow and no more than an NHLBI type B peri-stent dissection

Exclusion Criteria:

• Contraindication to anti-platelet agents & bleeding history within prior 3 months
• Known hypersensitivity or contraindication to any of the following medications: Heparin, Aspirin, Clopidogrel, limus related drug
• Prior history of the following presentations : Cerebral vascular accident (not including transient ischemic attack, Peripheral artery occlusive diseases, Thromboembolic disease, Stent thrombosis
• Severe hepatic dysfunction (3 times normal reference values)
• Significant renal dysfunction (Serum creatinine > 2.0 mg/dl)
• Significant leukopenia, neutropenia, thrombocytopenia, anemia, or known bleeding diathesis
• Cardiogenic shock
• LVEF < 40%
• Pregnant women or women with potential childbearing
• Life expectancy 3 year
• Overlapped DESs(only long lesion subgroup is possible overlapping)
• Left main disease requiring PCI
• Bifurcation lesion with 2-stent technique
• Target lesions with in-stent restenosis at the stented segment of DES or BMS
• Lesions with chronic total occlusion
• History of PCI with DES
• In-stent restenosis lesion

Contacts and Locations

Locations

Korea, Republic of

Severance Cardiovascular Hospital, Yonsei University College of Medicine

Seoul, Korea, Republic of, 120-752

Sponsors and Collaborators

Yonsei University

Investigators

• Principal Investigator: Myeong Ki Hong, MD, PhD; Severance Cardiovascular Hospital, Yonsei University College of Medicine

More Information

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

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.

Kim JS, Kang TS, Mintz GS, Park BE, Shin DH, Kim BK, Ko YG, Choi D, Jang Y, Hong MK. Randomized comparison of clinical outcomes between intravascular ultrasound and angiography-guided drug-eluting stent implantation for long coronary artery stenoses. JACC Cardiovasc Interv. 2013 Apr;6(4):369-76. doi: 10.1016/j.jcin.2012.11.009. Epub 2013 Mar 20.

Kim BK, Hong MK, Shin DH, Nam CM, Kim JS, Ko YG, Choi D, Kang TS, Park BE, Kang WC, Lee SH, Yoon JH, Hong BK, Kwon HM, Jang Y; RESET Investigators. A new strategy for discontinuation of dual antiplatelet therapy: the RESET Trial (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation). J Am Coll Cardiol. 2012 Oct 9;60(15):1340-8. doi: 10.1016/j.jacc.2012.06.043. Epub 2012 Sep 19.

• Responsible Party: Yonsei University
• ClinicalTrials.gov Identifier: NCT01145079 History of Changes
• Other Study ID Numbers: 4-2009-0115
• First Posted: June 16, 2010
• Last Update Posted: March 6, 2013
• Last Verified: March 2013

Additional relevant MeSH terms:

Coronary Artery Disease; Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Sirolimus; Everolimus; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antifungal Agents