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

October 3, 2017 updated by: Michael A. Horst, PhD, MPHS, MS, Lancaster General Hospital

The Effect of Inducing the Cytochrome P450 System on the Pharmacodynamic Efficacy of Clopidogrel

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

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Lancaster, Pennsylvania, United States, 17604
        • Lancaster General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AB: Placebo (A); St. Johns Wort (B)
Receive placebo for 7 days, 7 days washout and 7 days of St. Johns Wort
Drug: Placebo
Non-active placebo for 7 days: PO/TID
Drug: St. Johns Wort
For 7 days: 300mg PO/TID
Experimental: BA: St. Johns Wort (B); Placebo (A)
Receive St. Johns Wort for 7 days, 7 days washout and 7 days of placebo
Drug: Placebo
Non-active placebo for 7 days: PO/TID
Drug: St. Johns Wort
For 7 days: 300mg PO/TID

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean platelet reactivity (as measured in platelet reactivity units) on day 7 and day 21
Time Frame: Day 7 and Day 21
The investigators are comparing the mean platelet reactivity (as measured in platelet reactivity units) within subjects (treatment effect) between placebo and St. Johns Wort. In addition we will be assessing the period effect (difference between those getting treatment AB - placebo/St. Johns Wort and those getting treatment BA - St. Johns Wort/placebo).
Day 7 and Day 21

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Lancaster General Hospital

Collaborators

Louise von Hess Medical Research Institute
H G Barsumian MD Memorial Fund

Investigators

  • Principal Investigator: Kathy M Makkar, PharmD, Lancaster General Hospital
  • Principal Investigator: Roy S Small, MD, Lancaster General Hospital
  • Principal Investigator: Rupal P Dumasia, MD, Lancaster General Hospital
  • Principal Investigator: Jill A Rebuck, PharmD, Lancaster General Hospital
  • Principal Investigator: Michael A Horst, PhD, Lancaster General Research Institute
  • Principal Investigator: Yee M Lee, PharmD, Lancaster General Hospital
  • Principal Investigator: Richard D Paoletti, RPh, Lancaster General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2011

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

March 1, 2015

Study Registration Dates

First Submitted

March 28, 2011

First Submitted That Met QC Criteria

April 6, 2011

First Posted (Estimate)

April 7, 2011

Study Record Updates

Last Update Posted (Actual)

October 5, 2017

Last Update Submitted That Met QC Criteria

October 3, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010-56-LGH

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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