Trial | NCT01330589  Report issue

Title

Pharmacodynamic Study on Efficacy of Clopidogrel With St. John's Wort
The Effect of Inducing the Cytochrome P450 System on the Pharmacodynamic Efficacy of Clopidogrel

  • Phase

    N/A

  • Study Type

    Interventional

  • Status

    Withdrawn

  • Study Participants

    0
The purpose of this study is to evaluate whether patients post PCI receiving clopidogrel who are carriers of at least one CYP 2C19 loss-of-function allele may achieve improved pharmacodynamic efficacy of clopidogrel when treated with the CYP 2C19 enzyme inducing agent, St. John's wort, as compared with placebo.

Hypothesis

Reduced platelet reactivity is present in patients receiving St. John's wort as compared to placebo when utilized in combination with clopidogrel
The combination or St. John's wort and clopidogrel results in enhanced platelet inhibition
Objective The purpose of this study is to evaluate whether patients post PCI receiving clopidogrel who are carriers of at least one CYP 2C19 loss-of-function allele may achieve improved pharmacodynamic efficacy of clopidogrel when treated with the CYP 2C19 enzyme inducing agent, St. John's wort, as compared with placebo.

Specific Aims

To identify the difference in platelet reactivity in patients receiving St. John's wort or placebo
To characterize the difference in platelet inhibition in patients receiving St. John's wort or placebo

Hypothesis

Reduced platelet reactivity is present in patients receiving St. John's wort as compared to placebo when utilized in combination with clopidogrel
The combination or St. John's wort and clopidogrel results in enhanced platelet inhibition

Study Design The study is a prospective, randomized, double-blind, placebo-controlled, cross-over study of patients post PCI who require dual-antiplatelet therapy with aspirin and clopidogrel. Approximately 84 patients will be enrolled and undergo pharmacogenetic testing to assess clopidogrel responsiveness utilizing CYP P450 2C19 genotyping (Plavitest®). Based upon an assumption of 30% genetic non-responsiveness and a dropout rate of 20%, to achieve a final sample size of 20 subjects in the randomized crossover portion of the study, the investigators need to enroll approximately 84 subjects. Patients identified as carriers of at least one CYP 2C19 loss-of-function allele (i.e. clopidogrel reduced-metabolizers) will remain in the study and be randomly assigned to receive placebo or St. John's wort. Patients not carrying a CYP 2C19 loss-of-function allele (i.e. clopidogrel normal metabolizers) will not require any further follow-up as these patients are considered to display a normal response to clopidogrel. On day 7 following the initiation of the study drug, platelet function testing will be performed. Following a 7 day washout period, patients will be crossed over into the other study group to receive 7 days of study medication. On day 21, the patients will undergo platelet function testing and the study medication will be discontinued.
Study Started
Apr 30
2011
Primary Completion
Mar 31
2015
Study Completion
Mar 31
2015
Last Update
Oct 05
2017

Drug Placebo

Non-active placebo for 7 days: PO/TID

Drug St. Johns Wort

For 7 days: 300mg PO/TID

AB: Placebo (A); St. Johns Wort (B) Experimental

Receive placebo for 7 days, 7 days washout and 7 days of St. Johns Wort

BA: St. Johns Wort (B); Placebo (A) Experimental

Receive St. Johns Wort for 7 days, 7 days washout and 7 days of placebo

Criteria 

Inclusion Criteria:

Patients age 18 or older
Patients with a history of ACS and/or who receive PCI with stent placement at Lancaster General Hospital requiring dual antiplatelet therapy with aspirin and clopidogrel.

Exclusion Criteria:

Patients with active or any known history of bleeding such as gastrointestinal, intracranial, or any other bleeding diathesis
History of major surgery in the last year (any surgical procedure that involves general anesthesia or respiratory assistance)
Clinical findings associated with an increased risk of bleeding at the judgment of the investigator
Patients actively receiving anticoagulation therapy
Hemoglobin < 10 g/dL
Platelets < 150,000/mm3
Known hepatic dysfunction
History of intracranial malignancy or stroke
Patients receiving thienopyridines chronically prior to PCI
Concurrent use of CYP P450 2C19 substrates, or inhibiting/ inducing medications with the exception of proton pump inhibitors
Illicit drug or alcohol abuse
Daily treatment with nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors
Allergy to St. Johns wort or lactose
Patients expected to discontinue dual antiplatelet therapy prior to completion of the study protocol
Patients unable to adhere to the study protocol
No Results Posted