Help guide our efforts to modernize
Send us your comments by March 14, 2020. Menu

H2 Haplotype and CYP3As Polymorphisms and the Antiplatelet Response to Clopidogrel

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. Identifier: NCT00433784
Recruitment Status : Completed
First Posted : February 12, 2007
Last Update Posted : August 21, 2012
Information provided by:
Hopital du Sacre-Coeur de Montreal

Brief Summary:
The purpose of this study was to assess whether interpatient variability in the platelet response to clopidogrel is partly due to polymorphisms of the hepatic cytochrome P450 (CYP450)3A and of the clopidogrel-P2Y12 receptor genes.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Elective Percutaneous Coronary Intervention Drug: Clopidogrel Procedure: Blood sampling - platelet aggregation Procedure: Blood sampling - genotyping Phase 4

Detailed Description:

Clopidogrel owes its antiplatelet effect to irreversible inhibition of the purinergic platelet receptor, P2Y12. It is estimated that approximately 4%-30% of patients treated with conventional doses of clopidogrel do not display adequate platelet response. Moreover, patients with low response to clopidogrel may be at higher risk for atherothrombotic events. Clopidogrel, being a prodrug, requires oxidation by the hepatic cytochrome P450 (CYP450)3A to generate an active metabolite.The level of CYP3A4 activity has been shown to correlate with the inhibitory effect of clopidogrel on platelet aggregation in healthy volunteers. However, CYP3As expression and activity vary among individuals. It is estimated that most of this variability is caused by individual genetic makeup.Polymorphisms of the P2Y12 receptor may also play a role in the variability in clopidogrel response. The P2Y12-H2 haplotype was associated with higher maximal platelet aggregation in response to adenosine diphosphate (ADP) as compared to the P2Y12-H1 haplotype probably due to an increase in the number of receptors on the platelet surface. It has also been suggested that carriers of the H2 haplotype might be at higher risk of developing peripheral artery disease.

Comparisons: Presence of CYP3A5 polymorphism and of the H2 haplotype compared to absence of these polymorphisms on the antiplatelet response to clopidogrel across a wide range of clopidogrel dosing regimens in patients with suspected or demonstrated coronary artery disease (CAD) scheduled to undergo elective percutaneous coronary intervention (PCI).

Platelet aggregation was measured by optical aggregometry with (ADP) 20 μmol/L as the agonist in patients before clopidogrel initiation and at the time of diagnostic coronary angiography. Genotyping was performed by standard polymerase chain reaction (PCR) method to identify expressors of CYP3A5 and P2Y12 H2 haplotype carriers.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Diagnostic
Official Title: Evaluation of the Effect of the H2 Haplotype and CYP3As Polymorphisms on the Antiplatelet Response to Clopidogrel Given Before Elective Percutaneous Coronary Intervention
Study Start Date : September 2004
Study Completion Date : April 2006

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Effect of CYP3A5 polymorphisms and of the H2 haplotype on the inhibitory effect of clopidogrel on platelet aggregation at the time of diagnostic coronary angiography as measured by optical aggregometry with adenosine diphosphate (ADP) 20 μmol/L

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.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Documented coronary artery disease (CAD) requiring an elective diagnostic coronary angiography with or without percutaneous coronary intervention (PCI)

Exclusion Criteria:

  • Major bleeding disorders or active bleeding;
  • Acute MI within 14 days of recruitment;
  • Unstable angina with ST-segment changes of > or = 1 mm in at least two contiguous electrocardiographic leads at rest, a troponin level of > 0.06 ug/L or both within 14 days of recruitment;
  • Stroke within the last 3 months;
  • Platelet count < 100 x 109/L;
  • Prothrombin time > 1.5 times control;
  • Hematocrit < 25% or hemoglobin level < 100 g/L;
  • Alcohol or drug abuse;
  • Enrolment in other investigational drug trials within the previous month;
  • Use of thienopyridines, glycoprotein (GP) IIb/IIIa inhibitors, warfarin or acenocoumarol within the prior week;
  • Allergic reaction or any contraindication to clopidogrel or aspirin.

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 identifier (NCT number): NCT00433784

Layout table for location information
Canada, Quebec
Hôpital du Sacré-Coeur de Montréal
Montréal, Quebec, Canada, H4J 1C5
Sponsors and Collaborators
Hopital du Sacre-Coeur de Montreal
Layout table for investigator information
Principal Investigator: Jean G Diodati, MD Hopital du Sacre-Coeur de Montreal

Layout table for additonal information Identifier: NCT00433784    
Other Study ID Numbers: C.E.2004-06-24
First Posted: February 12, 2007    Key Record Dates
Last Update Posted: August 21, 2012
Last Verified: June 2008
Keywords provided by Hopital du Sacre-Coeur de Montreal:
platelet aggregation
H2 haplotype
Additional relevant MeSH terms:
Layout table for MeSH terms
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs