NCT01330589

Brief Summary

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

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Apr 2011

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 28, 2011

Completed
4 days until next milestone

Study Start

First participant enrolled

April 1, 2011

Completed
6 days until next milestone

First Posted

Study publicly available on registry

April 7, 2011

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
Last Updated

October 5, 2017

Status Verified

October 1, 2017

Enrollment Period

3.9 years

First QC Date

March 28, 2011

Last Update Submit

October 3, 2017

Conditions

Acute Coronary Syndrome

Keywords

Percutaneous coronary interventionClopidogrelSt. John's WortCYP 2C19 loss-of-function allele

Outcome Measures

Primary Outcomes (1)

  • Mean platelet reactivity (as measured in platelet reactivity units) on 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

Study Arms (2)

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

EXPERIMENTAL

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

Drug: PlaceboDrug: 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

Drug: PlaceboDrug: St. Johns Wort

Interventions

PlaceboDRUG

Non-active placebo for 7 days: PO/TID

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

For 7 days: 300mg PO/TID

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

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Lancaster General Hospital

Lancaster, Pennsylvania, 17604, United States

Location

Related Publications (12)

  • Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001 Aug 16;345(7):494-502. doi: 10.1056/NEJMoa010746.

    PMID: 11519503BACKGROUND

  • Steinhubl SR, Berger PB, Mann JT 3rd, Fry ET, DeLago A, Wilmer C, Topol EJ; CREDO Investigators. Clopidogrel for the Reduction of Events During Observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002 Nov 20;288(19):2411-20. doi: 10.1001/jama.288.19.2411.

    PMID: 12435254BACKGROUND

  • Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ; CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006 Apr 20;354(16):1706-17. doi: 10.1056/NEJMoa060989. Epub 2006 Mar 12.

    PMID: 16531616BACKGROUND

  • Kimura T, Morimoto T, Kozuma K, Honda Y, Kume T, Aizawa T, Mitsudo K, Miyazaki S, Yamaguchi T, Hiyoshi E, Nishimura E, Isshiki T; RESTART Investigators. Comparisons of baseline demographics, clinical presentation, and long-term outcome among patients with early, late, and very late stent thrombosis of sirolimus-eluting stents: Observations from the Registry of Stent Thrombosis for Review and Reevaluation (RESTART). Circulation. 2010 Jul 6;122(1):52-61. doi: 10.1161/CIRCULATIONAHA.109.903955. Epub 2010 Jun 21.

    PMID: 20566955BACKGROUND

  • Savi P, Herbert JM, Pflieger AM, Dol F, Delebassee D, Combalbert J, Defreyn G, Maffrand JP. Importance of hepatic metabolism in the antiaggregating activity of the thienopyridine clopidogrel. Biochem Pharmacol. 1992 Aug 4;44(3):527-32. doi: 10.1016/0006-2952(92)90445-o.

    PMID: 1510701BACKGROUND

  • Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, Braunwald E, Sabatine MS. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 Jan 22;360(4):354-62. doi: 10.1056/NEJMoa0809171. Epub 2008 Dec 22.

    PMID: 19106084BACKGROUND

  • Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N, Steg PG, Ferrieres J, Danchin N, Becquemont L; French Registry of Acute ST-Elevation and Non-ST-Elevation Myocardial Infarction (FAST-MI) Investigators. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009 Jan 22;360(4):363-75. doi: 10.1056/NEJMoa0808227. Epub 2008 Dec 22.

    PMID: 19106083BACKGROUND

  • Wang LS, Zhu B, Abd El-Aty AM, Zhou G, Li Z, Wu J, Chen GL, Liu J, Tang ZR, An W, Li Q, Wang D, Zhou HH. The influence of St John's Wort on CYP2C19 activity with respect to genotype. J Clin Pharmacol. 2004 Jun;44(6):577-81. doi: 10.1177/0091270004265642.

    PMID: 15145964BACKGROUND

  • Barnes PM, Powell-Griner E, McFann K, Nahin RL. Complementary and alternative medicine use among adults: United States, 2002. Adv Data. 2004 May 27;(343):1-19.

    PMID: 15188733BACKGROUND

  • Wang LS, Zhou G, Zhu B, Wu J, Wang JG, Abd El-Aty AM, Li T, Liu J, Yang TL, Wang D, Zhong XY, Zhou HH. St John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther. 2004 Mar;75(3):191-7. doi: 10.1016/j.clpt.2003.09.014.

    PMID: 15001970BACKGROUND

  • 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).

    BACKGROUND

  • Lau WC, Welch TD, Shields T, Rubenfire M, Tantry US, Gurbel PA. The effect of St John's Wort on the pharmacodynamic response of clopidogrel in hyporesponsive volunteers and patients: increased platelet inhibition by enhancement of CYP3A4 metabolic activity. J Cardiovasc Pharmacol. 2011 Jan;57(1):86-93. doi: 10.1097/FJC.0b013e3181ffe8d0.

    PMID: 20980920BACKGROUND

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Hypericum extract LI 160

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular Diseases

Study Officials

  • 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

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of Research

Study Record Dates

First Submitted

March 28, 2011

First Posted

April 7, 2011

Study Start

April 1, 2011

Primary Completion

March 1, 2015

Study Completion

March 1, 2015

Last Updated

October 5, 2017

Record last verified: 2017-10

Locations

US(1)