Optimal Duration of Clopidogrel in Second-Generation Drug-Eluting Stents

Phase 4

Completed

• Conditions: Ischemic Heart Disease
• Interventions: Drug: 6-month dual anti-platelet therapy; Drug: 12-month dual anti-platelet therapy; Device: Zotarolimus eluting stent; Device: Biolimus eluting stent

• Registration Number: NCT03056118
• Lead Sponsor: Gangnam Severance Hospital

Brief Summary

Investigators try to assess the safety of 6-months or 12-months maintenance of dual antiplatelet therapy (DAPT, aspirin + clopidogrel) in patients undergoing percutaneous coronary intervention using the Zotarolimus-eluting, Resolute Integrity™ stent (Medtronic Vascular Inc, Santa Rosa, CA) or the BioMatrix™ stent (Biosensors. Singapore).

Detailed Description

Dual antiplatelet therapy (DAPT) has proven the most effective treatment in reducing thrombotic complications after drug eluting stent (DES) implantation. Although the optimal duration of antiplatelet therapy is still under investigation, late stent thrombosis (ST) with DES has pushed the recommendation for duration of clopidogrel therapy for one year or more, in patients without risks for bleeding. However, recent controversies regarding the risk of stent thrombosis in patients receiving DES has brought up the issue of the appropriate duration of antiplatelet therapy after percutaneous coronary intervention, and a recent study reported that the use of extended DAPT for a period longer than 12 months in patients who had received DES was not significantly more effective than aspirin monotherapy in reducing the rate of myocardial infarction (MI) or death for cardiac causes.

Zotarolimus-eluting stent (Resolute Integrity™) and biolimus-eluting stent with biodegradable polymer system (BioMatrix™) share several similarities. Both stents are flexible thin strut stents eluting sirolimus-analogue drugs targeting at mammalian target of rapamycin. The advantages that Resolute Integrity™ stent strut is quite thin and coated with highly biocompatible polymer and BioMatrix™ stent has the abluminal drug coating system with biodegradable polymer might provide clinical studies showing that both stents are quite safe as well as efficacious. Moreover, recent report showed that continuation of clopidogrel for only 3 months after implantation of Endeavor stent seems to be safe in low-to-moderate coronary artery risk group. Based on these clinical evidences, the duration of DAPT continuation for 12 months or less after implantation of Resolute Integrity™ or BioMatrix™ stent, 'the second generation DES', would be safe, however, there are no data available about this. Therefore, the purpose of this study is to assess the safety of 6-months or 12-months maintenance of DAPT in patients undergoing percutaneous coronary intervention (PCI) using Resolute Integrity™ or BioMatrix™ stent.

Study Timeline

• Study Start: 2011-05-02
• Primary Completion: 2015-06-01
• Study Completion: 2015-09-07
• Status Verified: 2017-02
• Study First Submitted: 2017-02-08
• Study First Submitted QC: 2017-02-14
• Last Update Submitted: 2017-02-14
• Study First Posted: 2017-02-17
• Last Update Posted: 2017-02-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1368

Inclusion Criteria

1. Subject must be at least 20 years of age.
2. Subject must have evidence of myocardial ischemia (e.g. stable angina, non-ST elevation acute coronary syndrome, silent ischemia, positive functional study or a reversible changes in the electrocardiogram (ECG) consistent with ischemia).
3. Subject is able to verbally confirm understandings of risks, benefits and treatment alternatives of receiving the Resolute Integrity or BioMatrix stent and he/she or his/her legally authorized representative provides written informed consent prior to any study related procedure.

Exclusion Criteria

1. Acute ST elevation myocardial infarction
2. The patient has a known hypersensitivity or contraindication to any of the following medications: heparin, aspirin, clopidogrel, zotarolimus, biolimus, contrast media
3. Clinical conditions requiring systemic immune suppression over 2 weeks or anti-cancer therapy
4. Prior history of the following presentations: Thromboembolic disease, Stent thrombosis
5. Pregnant women or women with childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study.
6. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions.
7. Gastrointestinal or genitourinary bleeding within the prior 3 months, or major surgery within 2 months.
8. Current known current platelet count < 100,000 cells/mm3 or Hgb <10 g/dL.
9. 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
10. Patients with left ventricular ejection fraction < 35%
11. Patients with cardiogenic shock
12. Creatinine level > 2.4mg/dL
13. Severe hepatic dysfunction (aspartate aminotransferase and/or alanine aminotransferase ≥ 3 times upper normal reference values)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
6-month dual anti-platelet therapy	6-month dual anti-platelet therapy	maintain dual anti-platelet agents for 6 months
12-month dual anti-platelet therapy	12-month dual anti-platelet therapy	maintain dual anti-platelet agents for 12 months
Zotarolimus eluting stent arm	Zotarolimus eluting stent	implant with zotarolimus eluting stent (Resolute Integrity)
Biolimus eluting stent arm	Biolimus eluting stent	implant with biolimus eluting stent (Biomatrix)

Primary Outcome Measures

Name	Time	Method
A composite of major adverse cardiac events (MACE; cardiac death, target vessel MI and ischemia driven-target lesion revascularization; TLR)	12 months	1. Cardiac death: Any death due to proximate cardiac cause (eg, MI, low-output failure, fatal arrhythmia), unwitnessed death and death of unknown cause, and all procedure-related deaths, including those related to concomitant treatment, will be classified as cardiac death.; 2. MI Classification and Criteria for Diagnosis is defined by the Academic Research Consortium; 3. TLR is defined as any repeat percutaneous intervention of the target lesion or bypass surgery of the target vessel performed for restenosis or other complication of the target lesion. All TLRs should be classified prospectively as clinically indicated\* or not clinically indicated by the investigator prior to repeat angiography. An independent angiographic core laboratory should verify that the severity of percent diameter stenosis meets requirements for clinical indication and will overrule in cases where investigator reports are not in agreement.