Official Title: “PROlonging Dual Antiplatelet Treatment In Patients With Coronary Artery Disease After Graded Stent-Induced Intimal Hyperplasia studY”

The duration of dual antiplatelet treatment (i.e. asprin and thienopyridines, mainly clopidogrel) after drug-eluting stent implantation is highly debated. This study will evaluate the value of extending such treatment up to 2 years after the procedure as compared to conventional treatment according to our national health institute guidelines (i.e. 1 month after bare metal stent and 6 months after drug-eluting stent) on the composite endpoint of death and MI.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Placebo Control, Factorial Assignment, Efficacy Study

Study Primary Completion Date: December 2010

This is a randomized, multi-center, open-label, study to evaluate the efficacy and safety profile of prolonged dual antiplatelet treatment (i.e. up to 2-year) with aspirin and clopidogrel after coronary stenting compared to currently recommended antiplatelet regimens (i.e. dual antiplatelet treatment for 1 month after BMS or 6 months after DES implantation).

As the degree of intimal hyperplasia (IH) suppression provided by the coronary stent system may be expected to influence the comparison between conventional versus prolonged dual antiplatelet treatment (DAT), patients in each group will be further randomized to no (BMS), intermediate (Endeavor), moderately high (Taxus) or very high (Xience V) degree of IH suppression so to minimize the confounding role of IH suppression on the primary hypothesis.

Patients will be then follow-up on a clinical basis at 1, 6, 12, 18 and 24 months for the primary hypothesis and then every year up to five for secondary hypotheses. In the conventional dual antiplatelet therapy group receiving one or more BMS implantation at the time of PCI, length of DAT may be influenced by acuity of clinical presentation. According to the CURE study (JAMA. 2002 Nov 20;288(19):2411-20), patients presenting with non-ST segment elevation acute coronary syndromes may be felt to require longer than 1 month DAT. Thus, to impose 1-month only of DAT duration after PCI may be not regarded as conventional at current stage. Based on this consideration, the protocol will allow extension of DAT up to 6 months after PCI in the conventional BMS group in those patients satisfying the inclusion and exclusion criteria of the CURE study at discretion of the treating physician.

Dual antiplatelet treatment refers to the use of Aspirin at doses ranging from 75 up to 325 mg/day p.o. in conjunction with clopidogrel (75 mg/day).

Ticlopidine (250 mg/ twice a day) is a second-choice drug and it will be allowed in cases where clopidogrel is not well tolerated or unavailable.

Clopidogrel and ticlopidine are equipotent antiplatelet agents. Both of them belong the class of thienopyridines and they act by inhibiting the the P2Y12 ADP receptor on platelets.

Intervention(s) in this Clinical Trial

• Drug: clopidogrel treatment after bare metal stent implantation
  • extending use of clopidogrel on top of aspirin up to 24 months after coronary implantation of bare metal stent
• Drug: clopidogrel treatment after bare metal stent implantation
  • Adding clopidogrel on top of Aspirin according to the practice suggested by Italian national institute of health, i.e. 1 month after BMS implantation.
• Drug: clopidogrel after zotarolimus-eluting stent implantation
  • extending use of clopidogrel on top of aspirin up to 24 months after coronary implantation of zotarolimus-eluting stent coronary implantation
• Drug: clopidogrel after paclitaxel-eluting stent implantation
  • extending use of clopidogrel on top of aspirin up to 24 months after coronary implantation of paclitaxel-eluting stent
• Drug: clopidogrel after everolimus-eluting stent implantation
  • extending use of clopidogrel on top of aspirin up to 24 months after coronary implantation of Everolimus-eluting stent
• Drug: clopidogrel after zotarolimus-eluting stent implantation
  • Adding clopidogrel on top of Aspirin according to the practice suggested by Italian national institute of health, i.e. 6 month after DES implantation.
• Drug: clopidogrel after paclitaxel-eluting stent implantation
  • Adding clopidogrel on top of Aspirin according to the practice suggested by Italian national institute of health, i.e. 6 month after DES implantation.
• Drug: clopidogrel after everolimus-eluting stent implantation
  • Adding clopidogrel on top of Aspirin according to the practice suggested by Italian national institute of health, i.e. 6 month after DES implantation.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • treatment with Aspirin and clopidogrel for 24 months after coronary intervention with stents. This group of patients will be randomized in a 1:1:1:1 ratio to receive bare metal stent, Zotarolimus-eluting stent, paclitaxel-eluting stent or everolimus-eluting stent.
• Active Comparator: 2
  • Treatment with aspirin and clopidogrel for 1 or 6 month(s) after BMS or DES implantation, respectively. This group of patients will be randomized in a 1:1:1:1 ratio to receive bare metal stent, Zotarolimus-eluting stent, paclitaxel-eluting stent or everolimus-eluting stent

Primary Measures

• Composite of death or myocardial infarction occurring in the time window from 31 days and up to 24 months after intervention.
  • Time Frame: 24 months
    Safety Issue?: No

Secondary Measures

• To evaluate the effect of intimal hyperplasia inhibition by drug-release (i.e. different stent types) on the composite of death and myocardial infarction 2 years after intervention
  • Time Frame: 24 months
    Safety Issue?: No
• Composite of death or myocardial infarction up to 24 months after intervention
  • Time Frame: 24 months
    Safety Issue?: No
• Cumulative incidence of Stent thrombosis according to the academic consortium definition after 30 days and up to 24 months after intervention
  • Time Frame: 24 months
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Males or females ≥ 18 years of age with coronary artery disease with low, intermediate or high-risk coronary anatomy, which is considered suitable for PCI with stent placement.
• 2. Subjects who have provided written informed consent prior to initiation of any study-related procedures, prior to receiving any pre-procedural sedation and who agree to comply with all protocol-specified procedures.

Exclusion Criteria:

• 1. Women who are pregnant. Women of childbearing potential must have a negative pregnancy test (urine or serum HCG) within 7 days prior to randomization; as close to randomization as possible, within 24 hours preferred.
• 2. Allergy or intolerance to aspirin, or both clopidogrel and ticlopidine
• 3. Subjects with a contraindication to anticoagulation and/or increased bleeding risk:
• Past or present bleeding disorder including a history of the following within 1 month prior to randomization: clinically relevant gastrointestinal bleeding, gross (visible) hematuria,
• Planned major surgery including CABG after or within 1 month prior to randomization.
• Any subject with a known coagulopathy, platelet disorder, or history of thrombocytopenia.
• 4. Subjects with a history of cancer (limiting survival) not known to be disease free, with the exception of basal cell carcinoma of the skin.
• 5. History of clinically important, recent or ongoing alcohol abuse or other drug abuse.
• 6. Known platelet count <100,000/mm3 (<100 x 109/L).
• 7. Subjects who is unable to give informed consent and assurance for complete contact through 2 years.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Universitaria di Ferrara

Overall Clinical Trial Officials and Contacts

Marco Valgimigli, MD, PhD Principal Investigator University of Ferrara, Italy  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00611286

Study ID Number: SSD-03-I

ClinicalTrials.gov Identifier: NCT00611286

Health Authority: Italy: Ethics Committee