Clopidogrel and Response Variability Investigation Study 2

NCT00822666 | Completed Phase 3

• 1 other identifier: P070117
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the role of the genetic variant 2C19\*2 on the pharmacodynamic response as assessed by optical aggregometry and on the pharmacokinetic response as assessed by measuring active metabolites following an oral administration of a loading dose of 300/900mg of clopidogrel in patients with established coronary artery disease.

Conditions

Coronary Artery Disease

Keywords

Platelet aggregation; Platelet; Thrombosis; Clopidogrel

Outcome Measures

Primary Outcomes (1)

• Inhibition of residual platelet activity 6 hours after a loading dose of clopidogrel

  6 hours

Secondary Outcomes (5)

• Maximum platelet aggregation instead of IRPA

  during the study

• RPA with 5µM and 50 µM of ADP

  during the study

• 3. Measure of clopidogrel and its active metabolites (carboxylated and thiol) at different time points following the loading dose (H0, H1, H2 ,H6) with respect to the presence of the genetic variant CYP2C19*2

  H0, H1, H2, H6

• Relationship between active metabolites concentration and IRPA

  during the study

• Relationship between active metabolites and dose of clopidogrel

  during the study

Study Arms (2)

1

ACTIVE COMPARATOR

patients homozygous for the 2C19\*1 genetic variant

Drug: clopidogrel

2

EXPERIMENTAL

carriers of the 2C19\*2 genetic variant (homozygous or heterozygous)

Drug: clopidogrel

Interventions

clopidogrel DRUG

comparison of two loading strategies of clopidogrel (300mg vs 900mg) in the two genetic profiles

1; 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18
• Male gender
• Included in the AFIJI registry
• No high bleeding risk profile
• No recent history of acute coronary syndrome (\< 3 months)
• Written informed consent obtained
• Genotype CYP2C19 : \*1/\*1, \*1/\*2 ou \*2/\*2
• Genotype P2Y12 : H1/H1 ou H1/H2

You may not qualify if:

• Female gender
• Patient with a contraindication to clopidogrel
• Patient who has received a loading dose of clopidogrel in the past 7 days
• Patient treated with ticlopidine or GP2B/3A receptor antagonist prior to loading
• Non compliance
• Génotype P2Y12 : H2/H2.
• Patient treated with drugs interacting with platelet aggregation (NSAID, persantine, serotonin inhibitors )
• Patient treated with drugs interacting 2C19
• Not affiliated to the national health insurance
• Patient participating to another randomized study

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator

Study Sites (1)

Hopital la Pitié-Salpétrière Institut de cardiologie

Paris, 75013, France

Location

Related Publications (2)

• Hulot JS, Collet JP, Cayla G, Silvain J, Allanic F, Bellemain-Appaix A, Scott SA, Montalescot G. CYP2C19 but not PON1 genetic variants influence clopidogrel pharmacokinetics, pharmacodynamics, and clinical efficacy in post-myocardial infarction patients. Circ Cardiovasc Interv. 2011 Oct 1;4(5):422-8. doi: 10.1161/CIRCINTERVENTIONS.111.963025. Epub 2011 Oct 4.

  PMID: 21972404 DERIVED

• Collet JP, Hulot JS, Anzaha G, Pena A, Chastre T, Caron C, Silvain J, Cayla G, Bellemain-Appaix A, Vignalou JB, Galier S, Barthelemy O, Beygui F, Gallois V, Montalescot G; CLOVIS-2 Investigators. High doses of clopidogrel to overcome genetic resistance: the randomized crossover CLOVIS-2 (Clopidogrel and Response Variability Investigation Study 2). JACC Cardiovasc Interv. 2011 Apr;4(4):392-402. doi: 10.1016/j.jcin.2011.03.002.

  PMID: 21511218 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Thrombosis

Interventions

Clopidogrel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jean-Philippe Collet, MD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2009
• First Posted: January 14, 2009
• Study Start: October 1, 2008
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: December 11, 2012

Record last verified: 2009-01

Locations

FR (1)