Pharmacodynamic Study on Efficacy of Clopidogrel With St. John's Wort (INDUCE-it)

Lancaster General Hospital

Status: Withdrawn

Conditions: Acute Coronary Syndrome

Treatments: Drug: Placebo; Drug: St. Johns Wort

Study type: Interventional

Funder types: Other

Identifiers

NCT01330589

2010-56-LGH

Details and patient eligibility

About

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

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

Full description

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

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

Hypothesis

1. Reduced platelet reactivity is present in patients receiving St. John's wort as compared to placebo when utilized in combination with clopidogrel
2. 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups

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

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: St. Johns Wort

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

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: St. Johns Wort