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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by Lancaster General Hospital
Sponsor:
Collaborators:
H. G. Barsumian Memorial Fund
Louise von Hess Medical Research Institute
Information provided by (Responsible Party):
Michael A. Horst, PhD, MPHS, MS, Lancaster General Hospital
ClinicalTrials.gov Identifier:
NCT01330589
First received: March 28, 2011
Last updated: January 16, 2013
Last verified: January 2013
  Purpose

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

Condition Intervention
Acute Coronary Syndrome
Drug: Placebo
Drug: St. Johns Wort

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effect of Inducing the Cytochrome P450 System on the Pharmacodynamic Efficacy of Clopidogrel

Resource links provided by NLM:


Further study details as provided by Lancaster General Hospital:

Primary Outcome Measures:
  • Mean platelet reactivity (as measured in platelet reactivity units) on day 7 and day 21 [ Time Frame: Day 7 and Day 21 ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 84
Study Start Date: April 2011
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01330589

Contacts
Contact: Kathy M Makkar, Pharm.D. 717-544-7416 kamakkar@lghealth.org

Locations
United States, Pennsylvania
Lancaster General Hospital Recruiting
Lancaster, Pennsylvania, United States, 17604
Sponsors and Collaborators
Lancaster General Hospital
H. G. Barsumian Memorial Fund
Louise von Hess Medical Research Institute
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
  More Information

Publications:
Lau W, Carville D, Guyer K, Neer C. St. John's wort enhances the platelet inhibitor effect of clopidogrel in clopidogrel "resistant" healthy volunteers. J Am Coll Cardiol 2005;4:382A(abstract).
Lau WC, Welch TD, Shields TA, Rubenfire M, Gurbel PA. The effect of St. John's wort on the pharmacodynamic efficacy of clopidogrel in hyporesponsive volunteers. J Am Coll Cardiol 2010;55:A171(abstract).

Responsible Party: Michael A. Horst, PhD, MPHS, MS, Director of Research, Lancaster General Hospital
ClinicalTrials.gov Identifier: NCT01330589     History of Changes
Other Study ID Numbers: 2010-56-LGH
Study First Received: March 28, 2011
Last Updated: January 16, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Lancaster General Hospital:
Percutaneous coronary intervention
Clopidogrel
St. John's Wort
CYP 2C19 loss-of-function allele

Additional relevant MeSH terms:
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Clopidogrel
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 18, 2014