Platelet Inhibitory Effect of Clopidogrel in Patients Treated With Omeprazole, Pantoprazole, or Famotidine

This study has been completed.
Sponsor:
Collaborator:
Tel Aviv Medical Center
Information provided by (Responsible Party):
michal roll, Tel-Aviv Sourasky Medical Center
ClinicalTrials.gov Identifier:
NCT00950339
First received: April 19, 2009
Last updated: July 6, 2016
Last verified: July 2016

April 19, 2009
July 6, 2016
August 2009
June 2011   (final data collection date for primary outcome measure)
Platelet function as assessed by a CPA system [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00950339 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Platelet Inhibitory Effect of Clopidogrel in Patients Treated With Omeprazole, Pantoprazole, or Famotidine
Platelet Inhibitory Effect of Clopidogrel in Patients Treated With Omeprazole, Pantoprazole, or Famotidine

Current guidelines recommend the addition of proton pump inhibitors (PPI) to patients taking double anti-platelet therapy (Aspirin and Clopidogrel) to prevent upper GI bleeding1. Many post percutaneous coronary intervention (PCI) patients are treated with dual anti-platelet medications as well as PPI to prevent upper GI bleeding.

Recently, it was shown that PPI interact with the P450 system in the liver and reduce the platelet inhibitory effect of Clopidogrel2,3. Clopidogrel is activated by CYP2C19, which also metabolizes PPI4. Furthermore, a recent article showed increased mortality in patients taking PPI and clopidogrel compared with patients taking clopidogrel without PPI protection5. The degree of reduction in the platelet inhibitory properties of clopidogrel might vary among the different PPI4.

The use of PPI for GI protection in patients treated with dual anti-platelet therapy is not based on randomized trials, but rather on expert opinion. Since H2 blockers are also effective in preventing acid secretion and are not known to interact with the P450 system that affects clopidogrel, the investigators hypothesized that these group of drugs will not interfere with the positive antiplatelet effects of clopidogrel and therefore will offer a good alternative treatment option.

In this study we will compare 3 different anti-acids regimens and their effect on platelet function
Interventional
Phase 4
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Coronary Heart Disease
  • GI Bleeding
  • Drug: omeprazole, 20mg twice daily

    Each patient will undergo 3 phases of drug therapy:

    A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

    At the end of each phase- each patient will undergo the following evaluation:

    Platelet reactivity

    Other Name: PPI Platelet Inhibitory
  • Drug: famotidine 40mg twice daily

    Each patient will undergo 3 phases of drug therapy:

    A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

    At the end of each phase- each patient will undergo the following evaluation:

    Platelet reactivity

    Other Name: PPI Platelet Inhibitory
  • Drug: pantoprazole 40mg once daily

    Each patient will undergo 3 phases of drug therapy:

    A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

    At the end of each phase- each patient will undergo the following evaluation:

    Platelet reactivity

    Other Name: PPI Platelet Inhibitory
  • Experimental: 4 weeks of omeprazole, 20mg twice daily

    Each patient will undergo 3 phases of drug therapy:

    A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

    At the end of each phase- each patient will undergo the following evaluation:

    Platelet reactivity

    Interventions:
    • Drug: omeprazole, 20mg twice daily
    • Drug: famotidine 40mg twice daily
    • Drug: pantoprazole 40mg once daily
  • Experimental: 4 weeks of famotidine 40mg twice daily

    Each patient will undergo 3 phases of drug therapy:

    A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

    At the end of each phase- each patient will undergo the following evaluation:

    Platelet reactivity

    Interventions:
    • Drug: omeprazole, 20mg twice daily
    • Drug: famotidine 40mg twice daily
    • Drug: pantoprazole 40mg once daily
  • Experimental: 4 weeks of pantoprazole 40mg once daily

    Each patient will undergo 3 phases of drug therapy:

    A- 4 weeks of PPI treatment (omeprazole, 20mg twice daily)) B- 4 weeks of H2 blocker treatment (famotidine 40mg twice daily) C- 4 weeks of PPI treatment (pantoprazole 40mg once daily).

    At the end of each phase- each patient will undergo the following evaluation:

    Platelet reactivity

    Interventions:
    • Drug: omeprazole, 20mg twice daily
    • Drug: famotidine 40mg twice daily
    • Drug: pantoprazole 40mg once daily
Arbel Y, Birati EY, Finkelstein A, Halkin A, Kletzel H, Abramowitz Y, Berliner S, Deutsch V, Herz I, Keren G, Banai S. Platelet inhibitory effect of clopidogrel in patients treated with omeprazole, pantoprazole, and famotidine: a prospective, randomized, crossover study. Clin Cardiol. 2013 Jun;36(6):342-6. doi: 10.1002/clc.22117. Epub 2013 Apr 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
63
August 2011
June 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Subject is at least 18 years old.
  2. Subject is willing to comply with pre-specified follow-up evaluation and can be contacted by telephone.
  3. Use of Clopidogrel (>=75mg) and Aspirin(>=75mg) for at least 1 month.

Exclusion Criteria:

  1. Known allergy to PPI of H2 blockers
  2. Known thrombocytopenia or thrombocytopathia
  3. Subject is currently enrolled in another investigational study of a new drug, biologic or device at the time of study screening. NOTE: Subjects who are participating in the long term follow-up phase of a previously investigational and now FDA-approved product are not excluded by this criterion.
  4. Subject with symptomatic heart failure of LVEF ≤ 25%
  5. Acute myocardial infarction within the past 30 days.
  6. No acute inflammatory event during the past month (e.g. infection, autoimmune or acute coronary event)
  7. Concurrent medical condition with a life expectancy of less than 12 months.
  8. Known severe renal failure (serum creatinine level >2.5 mg/dl).
  9. History of bleeding diathesis or coagulopathy or inability or unwillingness to receive blood transfusions.
  10. Evidence of active gastrointestinal bleeding or a history of such bleeding that is not known to have been treated and proven to have resolved.
  11. History of hepatitis (viral, ischemic or chemically-induced); clinical jaundice, history of cirrhosis.
  12. Patient treated with anticoagulant medication (Coumadin, LMWH)
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Israel
 
NCT00950339
TASMC-09-SB-0196-09-TLV-CTIL
No
No
Not Provided
michal roll, Tel-Aviv Sourasky Medical Center
Tel-Aviv Sourasky Medical Center
Tel Aviv Medical Center
Study Chair: Shmuel Banai, MD Tel Aviv Medical Center, Israel
Tel-Aviv Sourasky Medical Center
July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP