Double Randomization of a Monitoring Adjusted Antiplatelet Treatment Versus a Common Antiplatelet Treatment for DES Implantation, and Interruption Versus Continuation of Double Antiplatelet Therapy

NCT00827411 | Completed Phase 4 DMC

• 1 other identifier: P080403
• Study Type: interventional
• Target: 2,500
• Locations: 1 country
• Sites: 1

Brief Summary

Our first hypothesis is that dose adjustment of aspirin and clopidogrel based on biological monitoring reduces the rate of severe cardiovascular complications compared to a conventional strategy in patients scheduled for drug eluting stent implantation and followed up for one year. Our second hypothesis is that interruption of clopidogrel / Prasugrel after one year of a combined therapy of clopidogrel/Prasugrel and aspirin is associated with a higher rate of severe cardiovascular complications as compared with patients in whom aspirin and clopidogrel / Prasugrel is maintained during the subsequent 6 months of follow-up.

Conditions

Coronary Artery Disease; Acute Coronary Syndrome

Keywords

Drug Eluting Stent; Percutaneous coronary intervention; Oral antiplatelet therapy; Clopidogrel/Aspirin; Acute Coronary Syndrome

Outcome Measures

Primary Outcomes (1)

• Composite endpoint of death, myocardial infarction, stroke, urgent coronary revascularization, stent thrombosis assessed at one year for the first hypothesis and between 6 up to 18 months of follow-up for the second hypothesis

  during the study (one year in both " monitoring " and " conventional " arms and during the periode from 6 up to 18 months in the "interruption" and "pursuit" arms)

Secondary Outcomes (8)

• Stent thrombosis and urgent coronary revascularization

  at month 12 and month 30

• Rate of individual event at one year follow-up in both " monitoring " and " conventional " arms but also during the period from one year up to 24 months in the " interruption " and " pursuit " arms.

  at month 12 and month 30

• Time delay from treatment interruption (randomization 2) to any thrombotic event (stent thrombosis, urgent revascularization, acute myocardial infarction, cardiac death) treatment interruption(randomisation 2)

  at month 12 and month 30

• Treatment compliance evaluated by the number of oral antiplatelet treatment in both arms and with respect to all individual events of the primary composite endpoint

  at month 12 and month 30

• Rate of use of GP IIb/IIIa receptor antagonists in both " monitoring " and " conventional " arms before percutaneous coronary intervention and in bail out situations and in both.

  at month 12 and month 30

Study Arms (4)

1: Monitoring Arm

EXPERIMENTAL

First randomization: Monitoring Arm: dose adjustment of both aspirin and clopidogrel in suboptimal responders identified based on a point of care assay (VerifyNow).

Drug: Aspirin and clopidogrel / Prasugrel; Device: VerifyNow

2: Conventional Arm

ACTIVE COMPARATOR

First randomization: Conventional Arm: fixed dose regiment of both aspirin and clopidogrel in all patients following DES implantation according to international guidelines

Drug: Aspirin and clopidogrel / Prasugrel

3: Pursuit Arm

EXPERIMENTAL

Second randomization after one year of follow-up: Pursuit Arm: Pursuit of a dual oral antiplatelet therapy (aspirin and clopidogrel) beyond one year

Drug: Aspirin and clopidogrel / Prasugrel

4: Interruption Arm

ACTIVE COMPARATOR

Second randomization after one year of follow-up: Interruption Arm: Interruption of clopidogrel therapy.

Drug: Aspirin

Interventions

Aspirin and clopidogrel / Prasugrel DRUG

modification of aspirin and clopidogrel/Prasugrel maintenance doses based on a biological assay

1: Monitoring Arm

VerifyNow DEVICE

point of care assay VerifyNow (ACCUMETRICS San Diego USA)

1: Monitoring Arm

Aspirin DRUG

Interruption of clopidogrel / Prasugrel after one year of follow-up

4: Interruption Arm

Eligibility Criteria

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

You may qualify if:

• Patients (≥18 years) in whom elective DES stent placement is scheduled after diagnostic angiography
• Patients not treated by GPIIb/IIIa inhibitors prior to randomization.
• Provided written consent for participation in the trial prior to any study-specific procedures or requirements.

You may not qualify if:

• Oral anticoagulation (Vitamin K Antagonists).
• Contraindication for aspirin and/or clopidogrel/Prasugrel or GPIIb/IIIa inhibitors or to increasing dose of clopidogrel or aspirin
• Ongoing or recent bleeding and/or recent major surgery (\<3 weeks)
• Severe liver dysfunction
• Thrombocytopenia (Platelet count \<80000/µl).
• IIb/IIIa inhibitors within a week prior to randomization
• STEMI presentation
• Patient at risk of poor compliance to the study
• Patient not affiliated to social security
• Pregnant women, no signed inform consent
• Any invasive or surgical planned intervention during the year after stent placement

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Allies in Cardiovascular Trials Initiatives and Organized: collaborator
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Sanofi: collaborator
• Bristol-Myers Squibb: collaborator
• Medtronic: collaborator
• Cordis US Corp.: collaborator
• Fondation de France: collaborator
• Diagnostica Stago: collaborator
• Boston Scientific Corporation: collaborator

Study Sites (1)

Institut de Cardiologie- Hopital la Pitié Salpétrière

Paris, 75013, France

Location

Related Publications (6)

• Collet JP, Cuisset T, Range G, Cayla G, Elhadad S, Pouillot C, Henry P, Motreff P, Carrie D, Boueri Z, Belle L, Van Belle E, Rousseau H, Aubry P, Monsegu J, Sabouret P, O'Connor SA, Abtan J, Kerneis M, Saint-Etienne C, Barthelemy O, Beygui F, Silvain J, Vicaut E, Montalescot G; ARCTIC Investigators. Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med. 2012 Nov 29;367(22):2100-9. doi: 10.1056/NEJMoa1209979. Epub 2012 Nov 4.

  PMID: 23121439 RESULT

• Collet JP, Cayla G, Cuisset T, Elhadad S, Range G, Vicaut E, Montalescot G. Randomized comparison of platelet function monitoring to adjust antiplatelet therapy versus standard of care: rationale and design of the assessment with a double randomization of (1) a fixed dose versus a monitoring-guided dose of aspirin and clopidogrel after DES implantation, and (2) treatment interruption versus continuation, 1 year after stenting (ARCTIC) study. Am Heart J. 2011 Jan;161(1):5-12.e5. doi: 10.1016/j.ahj.2010.09.029.

  PMID: 21167334 RESULT

• Lattuca B, Silvain J, Yan Y, Pouillot C, Cuisset T, Cayla G, Henry P, Diallo A, Elhadad S, Range G, Lhermusier T, Boueri Z, Motreff P, Carrie D, Vicaut E, Montalescot G, Collet JP. Reasons for the Failure of Platelet Function Testing to Adjust Antiplatelet Therapy: Pharmacodynamic Insights From the ARCTIC Study. Circ Cardiovasc Interv. 2019 Nov;12(11):e007749. doi: 10.1161/CIRCINTERVENTIONS.118.007749. Epub 2019 Nov 7.

  PMID: 31694410 DERIVED

• Collet JP, Hulot JS, Cuisset T, Range G, Cayla G, Van Belle E, Elhadad S, Rousseau H, Sabouret P, O'Connor SA, Abtan J, Kerneis M, Saint-Etienne C, Barthelemy O, Beygui F, Silvain J, Vicaut E, Montalescot G; ARCTIC investigators. Genetic and platelet function testing of antiplatelet therapy for percutaneous coronary intervention: the ARCTIC-GENE study. Eur J Clin Pharmacol. 2015 Nov;71(11):1315-24. doi: 10.1007/s00228-015-1917-9. Epub 2015 Aug 13.

  PMID: 26265231 DERIVED

• Collet JP, Silvain J, Barthelemy O, Range G, Cayla G, Van Belle E, Cuisset T, Elhadad S, Schiele F, Lhoest N, Ohlmann P, Carrie D, Rousseau H, Aubry P, Monsegu J, Sabouret P, O'Connor SA, Abtan J, Kerneis M, Saint-Etienne C, Beygui F, Vicaut E, Montalescot G; ARCTIC investigators. Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Lancet. 2014 Nov 1;384(9954):1577-85. doi: 10.1016/S0140-6736(14)60612-7. Epub 2014 Jul 15.

  PMID: 25037988 DERIVED

• Montalescot G, Range G, Silvain J, Bonnet JL, Boueri Z, Barthelemy O, Cayla G, Belle L, Van Belle E, Cuisset T, Elhadad S, Pouillot C, Henry P, Motreff P, Carrie D, Rousseau H, Aubry P, Monsegu J, Sabouret P, O'Connor SA, Abtan J, Kerneis M, Saint-Etienne C, Beygui F, Vicaut E, Collet JP; ARCTIC Investigators. High on-treatment platelet reactivity as a risk factor for secondary prevention after coronary stent revascularization: A landmark analysis of the ARCTIC study. Circulation. 2014 May 27;129(21):2136-43. doi: 10.1161/CIRCULATIONAHA.113.007524. Epub 2014 Apr 9.

  PMID: 24718568 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Acute Coronary Syndrome

Interventions

Aspirin; Clopidogrel; Prasugrel Hydrochloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Piperazines

Study Officials

• Gilles Montalescot, PUPH

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Jean-Philippe Collet, PH

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2009
• First Posted: January 22, 2009
• Study Start: January 1, 2009
• Primary Completion: March 1, 2012
• Study Completion: January 1, 2013
• Last Updated: April 12, 2013

Record last verified: 2013-04

Locations

FR (1)