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

• ClinicalTrials.gov Identifier: NCT03056118
• Recruitment Status: Completed
• First Posted: February 17, 2017
• Last Update Posted: February 17, 2017
• Sponsor: Gangnam Severance Hospital
• Information provided by (Responsible Party): Hyuck moon Kwon, Gangnam Severance Hospital

Tracking Information

• First Submitted Date: February 8, 2017
• First Posted Date: February 17, 2017
• Last Update Posted Date: February 17, 2017
• Actual Study Start Date: May 2, 2011
• Actual Primary Completion Date: June 1, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 14, 2017)

A composite of major adverse cardiac events (MACE; cardiac death, target vessel MI and ischemia driven-target lesion revascularization; TLR) [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Optimal Duration of Clopidogrel in Second-Generation Drug-Eluting Stents
• Official Title: Optimal Duration of Clopidogrel After Implantation of Second-Generation Drug-Eluting Stents (OPTIMA-C)
• 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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Ischemic Heart Disease

Intervention

• Drug: 6-month dual anti-platelet therapy
  Aspirin and P2Y12 inhibitor after percutaneous coronary intervention continues for 6 months
  Other Name: Aspirin and Clopidogrel
• Drug: 12-month dual anti-platelet therapy
  Aspirin and P2Y12 inhibitor after percutaneous coronary intervention continues for 12 months
  Other Name: Aspirin and Clopidogrel
• Device: Zotarolimus eluting stent
  Zotarolimus eluting stent is applied to coronary stenotic lesion
• Device: Biolimus eluting stent
  Biolimus eluting stent is applied to coronary stenotic lesion

Study Arms

• Experimental: 6-month dual anti-platelet therapy
  maintain dual anti-platelet agents for 6 months
  Intervention: Drug: 6-month dual anti-platelet therapy
• Active Comparator: 12-month dual anti-platelet therapy
  maintain dual anti-platelet agents for 12 months
  Intervention: Drug: 12-month dual anti-platelet therapy
• Active Comparator: Zotarolimus eluting stent arm
  implant with zotarolimus eluting stent (Resolute Integrity)
  Intervention: Device: Zotarolimus eluting stent
• Active Comparator: Biolimus eluting stent arm
  implant with biolimus eluting stent (Biomatrix)
  Intervention: Device: Biolimus eluting stent

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 14, 2017): 1368
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: September 7, 2015
• Actual Primary Completion Date: June 1, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT03056118
• Other Study ID Numbers: 3-2011-0054
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: If PI and scientific committee approve to share individual participant data to other researchers.

• Responsible Party: Hyuck moon Kwon, Gangnam Severance Hospital
• Study Sponsor: Gangnam Severance Hospital
• Collaborators: Not Provided

Investigators

• Principal Investigator: Hyuck moon Kwon; Gangnam Severance Hospital

• PRS Account: Gangnam Severance Hospital
• Verification Date: February 2017