Effect of Primidone on Platelet Responsiveness in Patients Determined to be Clopidogrel Resistant
The purpose of this study is to determine whether adding primidone will improve the metabolism of clopidogrel thereby increasing metabolite levels within the blood stream and platelet response to clopidogrel in patients who were previously found to lack adequate response to clopidogrel. This information could help overcome clopidogrel resistance in patients who are at risk for stroke or transient ischemic attack (TIA).
Secondary Stroke Prevention
|Study Design:||Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Effect of Primidone on Platelet Responsiveness in Patients Determined to be Clopidogrel Resistant|
- Platelet Aggregometry [ Time Frame: Platelet aggregometry will be performed at Visit 1 and Visit 2 which will be 20-28 days following Visit 1. ] [ Designated as safety issue: No ]Platelet Aggregometry will be used to assess platelet responsiveness to clopidogrel following treatment with investigational medication. Blood will be placed in plastic cuvettes and probes will be inserted. Wires on the probes measure platelet aggregation in electrical impedance. A baseline is obtained and then adenosine diphosphate (ADP) is added to cause aggregation. Clopidogrel prevents platelet aggregation through irreversible binding of its active metabolite to the ADP receptors on the platelet surface. The change in impedance from baseline is directly proportional to the extent of platelet aggregation and is expressed in ohms of resistance.
- Area Under the Curve of Clopidogrel Metabolite Levels [ Time Frame: Metabolite Levels Drawn 30 minutes, 1 hour, 2 hours, 3 hours and 4 hours post clopidogrel dose at Visit 1 and Visit 2 which will be 20-28 days following Visit 1. ] [ Designated as safety issue: No ]Whole blood from the subjects will be drawn 30 minutes, 1 hour, 2 hours, 3 hours and 4 hours post clopidogrel dose. Once the blood is drawn, the metabolite will be derivatized to keep the metabolite stable in blood. Derivatization of the metabolite, involves spiking blood samples with 2-bromo-3'methoxyacetophenone contained in an acetonitrile solution. Once derivatization has been done, metabolite levels will be analyzed using liquid chromatography mass spectrometry (LCMS). Once concentration levels of the active metabolite are known, the area under the curve will be calculated under trapezoid rule (linear up, log down).
|Study Start Date:||August 2013|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Participants will receive primidone in addition to their clopidogrel regimen. For the first 3 days of the study, participants will take 125 mg of primidone (one-half tablet). After 3 days of 125 mg, the primidone dose will be increased to 250 mg (1 tablet) taken at bedtime for the next 17-25 days. The participant will then be asked to return and be retested.
Primidone is an antiepileptic used for the management of generalized tonic-clonic seizures and for the management of complex partial seizures. One of primidone's active metabolite is phenobarbital, which is a potent cytochrome P450 inducer. In this study, primidone will be used to induce CYP 1A2 in order to provide more efficient metabolism of clopidogrel to its active form
Other Name: Mysoline (brand)
Please refer to this study by its ClinicalTrials.gov identifier: NCT02008123
|United States, New York|
|Dent Neurologic Institute|
|Amherst, New York, United States, 14226|
|Principal Investigator:||Vernice Bates, M.D.||Dent Neurologic Institute|