Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
Text Size

Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke (AAPIX)

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2015 by Centre Hospitalier Universitaire de Saint Etienne
Sponsor:
Collaborator:
Groupe de Recherche sur la Thrombose
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier:
NCT01955642
First received: September 27, 2013
Last updated: January 28, 2015
Last verified: January 2015
History of Changes
  Purpose

Ischemic stroke (AIC) is the leading cause of non-traumatic disability in adults, the second leading cause of dementia and the third leading cause of death in France.

Clopidogrel is one of the recommended first line in the secondary prevention of AIC non cardioembolic origin. However recurrences occur in approximately 9% of patients receiving clopidogrel. Some studies in patients with coronary artery disease have made ​​the connection between these treatment failures and non-biological response to clopidogrel. This non-biological response is found for approximately 30% to 50% of patients. Several mechanisms may explain this non-response. The most accepted mechanism is pharmacokinetic. Indeed, clopidogrel is a prodrug that requires intestinal absorption by P-glycoprotein (PGP) and a transformation by hepatic cytochrome into active metabolites. The genetic polymorphism of proteins involved in these two steps explain the low plasma concentration of active metabolites and thus the low efficacy of clopidogrel in some patients.

A new pharmacodynamic hypothesis suggests the involvement of platelet alpha 2-adrenergic receptors. The activation of these receptors potentiates signaling pathway P2Y12 receptor (channel inhibited by clopidogrel) and helps reduce platelet aggregation inhibiting response to clopidogrel.


Condition Intervention
Brain Ischemia
Ischemic Attack
 Drug: Clopidogrel

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Evaluation of the Biological Response to Clopidogrel in Patients With Ischemic Stroke : Role of Platelet alpha2-adrenergic Receptors

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Centre Hospitalier Universitaire de Saint Etienne:

Primary Outcome Measures:
  • adrenergic component of the platelet response [ Time Frame: 5 days after taking clopidogrel ] [ Designated as safety issue: No ]
    adrenergic component of the platelet response is estimated by the difference between the maximum percentage of platelet aggregation by light transmission aggregometry (LTA) with the addition of ADP(adenosine diphosphate) + ADP versus selective agonist (epinephrine)


Secondary Outcome Measures:
  • VASP-CMF [ Time Frame: After 5 days taking clopidogrel ] [ Designated as safety issue: No ]
    Platelet reactivity index (PRI) by VASP CMF (flow cytometry) method

  • ELISA VASP [ Time Frame: After 5 days taking clopidogrel ] [ Designated as safety issue: No ]
    Platelet reactivity index (PRI-ELISA) using ELISA VASP

  • active metabolite of clopidogrel [ Time Frame: After 5 days taking clopidogrel ] [ Designated as safety issue: No ]
    Rate of residual plasma active metabolite of clopidogrel (R-130964)

  • Genotyping of MDR-1 and P450 2C19 [ Time Frame: After 5 days taking clopidogrel ] [ Designated as safety issue: No ]
    Genotyping of MDR-1 and P450 2C19


Biospecimen Retention:   Samples With DNA

Blood DNA
Estimated Enrollment: 80
Study Start Date: September 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
AVC
Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
 Drug: Clopidogrel
75 mg milligrams per days of PLAVIX
Other Name: PLAVIX(R)

Detailed Description:

Interest in the biological response to clopidogrel in the AIC is innovative because few data are available in this area. In addition to testing a new pharmacodynamic hypothesis, we also wish to study and compare other measures of platelet function methods in order to be able to use commonly in treatment decisions.

  Eligibility
Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications

Criteria

Inclusion Criteria:

  • Consent signed
  • Patients with non-cardioembolic AIC requiring initiation of treatment with clopidogrel as usual indications
  • normal standard biological tests

Exclusion Criteria:

  • Need to continue aspirin therapy
  • Patients with a recurrence of clopidogrel AIC
  • Patient already tacking clopidogrel
  • Drugs interfering with the adrenergic system alpha blockers, alpha 2 receptor agonists (alpha-methyldopa) and alpha2 receptor inhibitors (Mianserin, Mirtazapine, yohimbine)
  • Contra indication of clopidogrel and / or any of its excipients
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01955642

Contacts
Contact: Jerome VARVAT, MD (0)477127770 ext +33 jerome.varvat@chu-st-etienne.fr
Contact: Nora MALLOUK, PhD (0)47710281 ext +33 nora.mallouk@chu-st-etienne.fr

Locations
France
CHU de Saint-Etienne Recruiting
Saint-etienne, France, 42000
Principal Investigator: Jerome VARVAT, MD         
Sub-Investigator: Pierre GARNIER, MD         
Sub-Investigator: Magali EPINAT, MD         
Sub-Investigator: Sandrine ACCASSAT, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Saint Etienne
Groupe de Recherche sur la Thrombose
Investigators
Principal Investigator: Jerome VARVAT, MD CHU de Saint-Etienne
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Saint Etienne
ClinicalTrials.gov Identifier: NCT01955642     History of Changes
Other Study ID Numbers: 1208094, 2013-000313-20
Study First Received: September 27, 2013
Last Updated: January 28, 2015
Health Authority: France: French Data Protection Authority
France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Centre Hospitalier Universitaire de Saint Etienne:
Clopidogrel
Brain Ischemia
Ischemic attack
Biological response to clopidogrel

Additional relevant MeSH terms:
Brain Ischemia
Brain Diseases
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Vascular Diseases
Clopidogrel
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
 Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on March 03, 2015