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Synergy Between Stent and Drugs to Avoid Ischemic Recurrences After Percutaneous Coronary Intervention (PRODIGY)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00611286
First Posted: February 8, 2008
Last Update Posted: October 10, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Marco Valgimigli, Università degli Studi di Ferrara
  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 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (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:


Further study details as provided by Marco Valgimigli, 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 ]

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 ]
  • Composite of death or myocardial infarction up to 24 months after intervention [ Time Frame: 24 months ]
  • 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 ]

Estimated Enrollment: 1700
Study Start Date: December 2006
Study Completion Date: October 2012
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

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Franzone A, Piccolo R, Gargiulo G, Ariotti S, Marino M, Santucci A, Baldo A, Magnani G, Moschovitis A, Windecker S, Valgimigli M. Prolonged vs Short Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With or Without Peripheral Arterial Disease: A Subgroup Analysis of the PRODIGY Randomized Clinical Trial. JAMA Cardiol. 2016 Oct 1;1(7):795-803. doi: 10.1001/jamacardio.2016.2811.
Gargiulo G, Costa F, Ariotti S, Biscaglia S, Campo G, Esposito G, Leonardi S, Vranckx P, Windecker S, Valgimigli M. Impact of proton pump inhibitors on clinical outcomes in patients treated with a 6- or 24-month dual-antiplatelet therapy duration: Insights from the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY trial. Am Heart J. 2016 Apr;174:95-102. doi: 10.1016/j.ahj.2016.01.015. Epub 2016 Jan 25.
Costa F, Tijssen JG, Ariotti S, Giatti S, Moscarella E, Guastaroba P, De Palma R, Andò G, Oreto G, Zijlstra F, Valgimigli M. Incremental Value of the CRUSADE, ACUITY, and HAS-BLED Risk Scores for the Prediction of Hemorrhagic Events After Coronary Stent Implantation in Patients Undergoing Long or Short Duration of Dual Antiplatelet Therapy. J Am Heart Assoc. 2015 Dec 7;4(12). pii: e002524. doi: 10.1161/JAHA.115.002524.
Costa F, Adamo M, Ariotti S, Ferrante G, Navarese EP, Leonardi S, Garcia-Garcia H, Vranckx P, Valgimigli M. Left main or proximal left anterior descending coronary artery disease location identifies high-risk patients deriving potentially greater benefit from prolonged dual antiplatelet therapy duration. EuroIntervention. 2016 Feb;11(11):e1222-30. doi: 10.4244/EIJY15M08_04.
Costa F, Vranckx P, Leonardi S, Moscarella E, Ando G, Calabro P, Oreto G, Zijlstra F, Valgimigli M. Impact of clinical presentation on ischaemic and bleeding outcomes in patients receiving 6- or 24-month duration of dual-antiplatelet therapy after stent implantation: a pre-specified analysis from the PRODIGY (Prolonging Dual-Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia) trial. Eur Heart J. 2015 May 21;36(20):1242-51. doi: 10.1093/eurheartj/ehv038. Epub 2015 Feb 25.
Valgimigli M, Tebaldi M, Borghesi M, Vranckx P, Campo G, Tumscitz C, Cangiano E, Minarelli M, Scalone A, Cavazza C, Marchesini J, Parrinello G; PRODIGY Investigators. Two-year outcomes after first- or second-generation drug-eluting or bare-metal stent implantation in all-comer patients undergoing percutaneous coronary intervention: a pre-specified analysis from the PRODIGY study (PROlonging Dual Antiplatelet Treatment After Grading stent-induced Intimal hyperplasia studY). JACC Cardiovasc Interv. 2014 Jan;7(1):20-8. doi: 10.1016/j.jcin.2013.09.008. Epub 2013 Dec 11.
Campo G, Tebaldi M, Vranckx P, Biscaglia S, Tumscitz C, Ferrari R, Valgimigli M. Short- versus long-term duration of dual antiplatelet therapy in patients treated for in-stent restenosis: a PRODIGY trial substudy (Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia). J Am Coll Cardiol. 2014 Feb 18;63(6):506-12. doi: 10.1016/j.jacc.2013.09.043. Epub 2013 Oct 23.
Valgimigli M, Borghesi M, Tebaldi M, Vranckx P, Parrinello G, Ferrari R; PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY Investigators. Should duration of dual antiplatelet therapy depend on the type and/or potency of implanted stent? A pre-specified analysis from the PROlonging Dual antiplatelet treatment after Grading stent-induced Intimal hyperplasia studY (PRODIGY). Eur Heart J. 2013 Mar;34(12):909-19. doi: 10.1093/eurheartj/ehs460. Epub 2013 Jan 12.
Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C, Castriota F, Colombo F, Tebaldi M, Fucà G, Kubbajeh M, Cangiano E, Minarelli M, Scalone A, Cavazza C, Frangione A, Borghesi M, Marchesini J, Parrinello G, Ferrari R; Prolonging Dual Antiplatelet Treatment After Grading Stent-Induced Intimal Hyperplasia Study (PRODIGY) Investigators. Short- versus long-term duration of dual-antiplatelet therapy after coronary stenting: a randomized multicenter trial. Circulation. 2012 Apr 24;125(16):2015-26. doi: 10.1161/CIRCULATIONAHA.111.071589. Epub 2012 Mar 21.
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. doi: 10.1016/j.ahj.2010.07.034.

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
First Submitted: December 26, 2007
First Posted: February 8, 2008
Last Update Posted: October 10, 2012
Last Verified: October 2012

Keywords provided by Marco Valgimigli, 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
Paclitaxel
Albumin-Bound Paclitaxel
Everolimus
Sirolimus
Aspirin
Ticlopidine
Clopidogrel
Purinergic P2Y Receptor Antagonists
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents


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