Synergy Between Stent and Drugs to Avoid Ischemic Recurrences After Percutaneous Coronary Intervention - Full Text View

Sponsor:	Marco Valgimigli
Information provided by (Responsible Party):	Marco Valgimigli, Università degli Studi di Ferrara
ClinicalTrials.gov Identifier:	NCT00611286

Purpose

The duration of dual antiplatelet treatment (i.e. asprin and 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. minimum 1 month after bare metal stent and 6 months after drug-eluting stent) on the composite endpoint of death, MI or stroke.

Condition	Intervention	Phase
Coronary Artery Disease	Drug: clopidogrel treatment after bare metal stent implantation Drug: clopidogrel after zotarolimus-eluting stent implantation Drug: clopidogrel after paclitaxel-eluting stent implantation Drug: clopidogrel after everolimus-eluting stent implantation	Phase IV

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	PROlonging Dual Antiplatelet Treatment In Patients With Coronary Artery Disease After Graded Stent-induced Intimal Hyperplasia studY

Resource links provided by NLM:

MedlinePlus related topics: Coronary Artery Disease Heart Attack

Drug Information available for: Paclitaxel Sirolimus Clopidogrel Clopidogrel Bisulfate Everolimus CCI 779

U.S. FDA Resources

Further study details as provided by Università degli Studi di Ferrara:

Primary Outcome Measures:

Composite of death, myocardial infarction or stroke occurring in the time window from 31 days and up to 24 months after intervention. [ Time Frame: 24 months ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as safety issue: No ]
Composite of death or myocardial infarction up to 24 months after intervention [ Time Frame: 24 months ] [ Designated as 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	1700
Study Start Date:	December 2006
Estimated Study Completion Date:	December 2018
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	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 Other Names: oral ADP receptor blockers thienopyridines 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 Other Names: ADP recepots blockers p2y12 receptor blockers 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 Other Names: ADP receptor blockers P2Y12 receptor blocker 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 Other Names: ADP receptor blockers P2Y12 receptor blocker
Active Comparator: 2 Treatment with aspirin and clopidogrel for minimum 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	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. Other Names: Oral ADP receptor blocker thienopyridines 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. Other Names: ADP receptor blockers P2Y12 receptor blocker 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. Other Names: ADP receptor blockers P2Y12 receptor blockers 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. Other Names: ADP receptor blockers P2Y12 receptor blockers

Arms

Assigned Interventions

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.

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

Other Names:

oral ADP receptor blockers
thienopyridines

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

Other Names:

ADP recepots blockers
p2y12 receptor blockers

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

Other Names:

ADP receptor blockers
P2Y12 receptor blocker

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

Other Names:

ADP receptor blockers
P2Y12 receptor blocker

Active Comparator: 2

Treatment with aspirin and clopidogrel for minimum 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

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.

Other Names:

Oral ADP receptor blocker
thienopyridines

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.

Other Names:

ADP receptor blockers
P2Y12 receptor blocker

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.

Other Names:

ADP receptor blockers
P2Y12 receptor blockers

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.

Other Names:

ADP receptor blockers
P2Y12 receptor blockers

Detailed Description:

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 minimum 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.Extension of DAt up to 6 months after BMS in patients with STEMI is not recommended byt will be allowed as per protocol

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.
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:

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.
Allergy or intolerance to aspirin, or both clopidogrel and ticlopidine
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.
Subjects with a history of cancer (limiting survival) not known to be disease free, with the exception of basal cell carcinoma of the skin.
History of clinically important, recent or ongoing alcohol abuse or other drug abuse.
Known platelet count <100,000/mm3 (<100 x 109/L).
Subjects who is unable to give informed consent and assurance for complete contact through 2 years.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00611286

Locations

Italy
Azienda Ospedaliera Universitaria di Ferrara
Ferrara, Emilia Romagna, Italy, 44100

Sponsors and Collaborators

Marco Valgimigli

Investigators

Principal Investigator:

Marco Valgimigli, MD, PhD

University of Ferrara, Italy

More Information

No publications provided by Università degli Studi di Ferrara

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

Valgimigli M, Campo G, Percoco G, Monti M, Ferrari F, Tumscitz C, Zuffi A, Colombo F, Kubbajeh M, Cavazza C, Cangiano E, Tebaldi M, Minarelli M, Arcozzi C, Scalone A, Frangione A, Borghesi M, Marchesini J, Parrinello G, Ferrari R. Randomized comparison of 6- versus 24-month clopidogrel therapy after balancing anti-intimal hyperplasia stent potency in all-comer patients undergoing percutaneous coronary intervention Design and rationale for the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia study (PRODIGY). Am Heart J. 2010 Nov;160(5):804-11.

Responsible Party:	Marco Valgimigli, Head of the Catheterization laboratory, Università degli Studi di Ferrara
ClinicalTrials.gov Identifier:	NCT00611286 History of Changes
Other Study ID Numbers:	SSD-03-I
Study First Received:	December 26, 2007
Last Updated:	October 26, 2011
Health Authority:	Italy: Ethics Committee

Keywords provided by Università degli Studi di Ferrara:

Drug-eluting stent
clopidogrel
bare metal stent
landmark analysis
Patients with coronary artery disease

Additional relevant MeSH terms:

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Clopidogrel
Ticlopidine
Purinergic P2Y Receptor Antagonists
Everolimus
Sirolimus
Paclitaxel
Platelet Aggregation Inhibitors

Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cardiovascular Agents
Immunosuppressive Agents
Immunologic Factors
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on February 09, 2012