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

NCT00611286 | Completed Phase 4 DMC

• 1 other identifier: SSD-03-I
• Study Type: interventional
• Target: 1,700
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Coronary Artery Disease

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Composite of death, myocardial infarction or stroke occurring in the time window from 31 days and up to 24 months after intervention.

  24 months

Secondary Outcomes (3)

• 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

  24 months

• Composite of death or myocardial infarction up to 24 months after intervention

  24 months

• Cumulative incidence of Stent thrombosis according to the academic consortium definition after 30 days and up to 24 months after intervention

  24 months

Study Arms (2)

1

EXPERIMENTAL

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; Drug: clopidogrel after zotarolimus-eluting stent implantation; Drug: clopidogrel after paclitaxel-eluting stent implantation; Drug: clopidogrel after everolimus-eluting stent implantation

2

ACTIVE COMPARATOR

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; Drug: clopidogrel after zotarolimus-eluting stent implantation; Drug: clopidogrel after paclitaxel-eluting stent implantation; Drug: clopidogrel after everolimus-eluting stent implantation

Interventions

clopidogrel treatment after bare metal stent implantation DRUG

extending use of clopidogrel on top of aspirin up to 24 months after coronary implantation of bare metal stent

Also known as: oral ADP receptor blockers, thienopyridines

1

clopidogrel after zotarolimus-eluting stent implantation DRUG

extending use of clopidogrel on top of aspirin up to 24 months after coronary implantation of zotarolimus-eluting stent coronary implantation

Also known as: ADP recepots blockers, p2y12 receptor blockers

1

clopidogrel after paclitaxel-eluting stent implantation DRUG

extending use of clopidogrel on top of aspirin up to 24 months after coronary implantation of paclitaxel-eluting stent

Also known as: ADP receptor blockers, P2Y12 receptor blocker

1

clopidogrel after everolimus-eluting stent implantation DRUG

extending use of clopidogrel on top of aspirin up to 24 months after coronary implantation of Everolimus-eluting stent

Also known as: ADP receptor blockers, P2Y12 receptor blocker

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Marco Valgimigli: lead

Study Sites (1)

Azienda Ospedaliera Universitaria di Ferrara

Ferrara, Emilia-Romagna, 44100, Italy

Location

Related Publications (13)

• Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

  PMID: 35224730 DERIVED

• Gargiulo G, Heg D, Ferrari F, Percoco G, Campo G, Tumscitz C, Colombo F, Zuffi A, Castriota F, Cremonesi A, Windecker S, Valgimigli M. Stent and Dual Antiplatelet Therapy Duration Comparisons in the Setting of a Multicenter Randomized Controlled Trial: Can the Operator Experience Affect the Study Results? J Am Heart Assoc. 2017 Dec 23;6(12):e007150. doi: 10.1161/JAHA.117.007150.

  PMID: 29275371 DERIVED

• Piccolo R, Gargiulo G, Franzone A, Santucci A, Ariotti S, Baldo A, Tumscitz C, Moschovitis A, Windecker S, Valgimigli M. Use of the Dual-Antiplatelet Therapy Score to Guide Treatment Duration After Percutaneous Coronary Intervention. Ann Intern Med. 2017 Jul 4;167(1):17-25. doi: 10.7326/M16-2389. Epub 2017 Jun 13.

  PMID: 28605779 DERIVED

• 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.

  PMID: 27572001 DERIVED

• 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.

  PMID: 26995375 DERIVED

• Costa F, Tijssen JG, Ariotti S, Giatti S, Moscarella E, Guastaroba P, De Palma R, Ando 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):e002524. doi: 10.1161/JAHA.115.002524.

  PMID: 26643501 DERIVED

• 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.

  PMID: 26342472 DERIVED

• 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.

  PMID: 25718355 DERIVED

• 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.

  PMID: 24332420 DERIVED

• 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.

  PMID: 24161321 DERIVED

• 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.

  PMID: 23315904 DERIVED

• Valgimigli M, Campo G, Monti M, Vranckx P, Percoco G, Tumscitz C, Castriota F, Colombo F, Tebaldi M, Fuca 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.

  PMID: 22438530 DERIVED

• 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.

  PMID: 21095265 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Purinergic P2Y Receptor Antagonists; Thienopyridines

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Marco Valgimigli, MD, PhD

  University of Ferrara, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of the Catheterization laboratory

Study Record Dates

• First Submitted: December 26, 2007
• First Posted: February 8, 2008
• Study Start: December 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: October 1, 2012
• Last Updated: October 10, 2012

Record last verified: 2012-10

Locations

IT (1)