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

NCT01955642 | Completed

• 2 other identifiers: 12080942013-000313-20
• Study Type: observational
• Target: 91
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Brain Ischemia; Ischemic Attack

Keywords

Clopidogrel; Brain Ischemia; Ischemic attack; Biological response to clopidogrel

Outcome Measures

Primary Outcomes (1)

• adrenergic component of the platelet response

  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)

  5 days after taking clopidogrel

Secondary Outcomes (4)

• VASP-CMF

  After 5 days taking clopidogrel

• ELISA VASP

  After 5 days taking clopidogrel

• active metabolite of clopidogrel

  After 5 days taking clopidogrel

• Genotyping of MDR-1 and P450 2C19

  After 5 days taking clopidogrel

Study Arms (1)

AVC

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

Drug: Clopidogrel

Interventions

Clopidogrel DRUG

75 mg milligrams per days of PLAVIX

Also known as: PLAVIX(R)

AVC

Eligibility Criteria

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

Study Population

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

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Groupe de Recherche sur la Thrombose: collaborator

Study Sites (1)

CHU de Saint-Etienne

Saint-Etienne, 42000, France

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood DNA

MeSH Terms

Conditions

Brain Ischemia

Interventions

Clopidogrel

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

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

• Jerome VARVAT, MD

  CHU de Saint-Etienne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2013
• First Posted: October 7, 2013
• Study Start: September 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 31, 2015

Record last verified: 2015-12

Locations

FR (1)