Optimal Duration of Clopidogrel in Second-Generation Drug-Eluting Stents (OPTIMA-C)

Yonsei University Health System (YUHS)

Status and phase: Completed; Phase 4

Conditions: Ischemic Heart Disease

Treatments: Drug: 6-month dual anti-platelet therapy; Device: Zotarolimus eluting stent; Device: Biolimus eluting stent; Drug: 12-month dual anti-platelet therapy

Study type: Interventional

Funder types: Other

Identifiers

NCT03056118

3-2011-0054

Details and patient eligibility

About

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).

Full 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.

Enrollment: 1,368 patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

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1,368 participants in 4 patient groups

6-month dual anti-platelet therapy

Experimental group

Description:

maintain dual anti-platelet agents for 6 months

Treatment:

Drug: 6-month dual anti-platelet therapy

12-month dual anti-platelet therapy

Active Comparator group

Description:

maintain dual anti-platelet agents for 12 months

Treatment:

Drug: 12-month dual anti-platelet therapy

Zotarolimus eluting stent arm

Active Comparator group

Description:

implant with zotarolimus eluting stent (Resolute Integrity)

Treatment:

Device: Zotarolimus eluting stent

Biolimus eluting stent arm

Active Comparator group

Description:

implant with biolimus eluting stent (Biomatrix)

Treatment:

Device: Biolimus eluting stent