Clinical trial NCT00950339: Platelet Inhibitory Effect of Clopidogrel in Patients Treated With Omeprazole, Pantoprazole, or Famotidine
Official title: Platelet Inhibitory Effect of Clopidogrel in Patients Treated With Omeprazole, Pantoprazole, or Famotidine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Heart Disease
GI Bleeding
Keywords: GI bleeding
clopidogrel
aspirin
prevention
angiography
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Tel Aviv Medical Center
First posted: 2009-07-31
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: In this study we will compare 3 different anti-acids regimens and their effect on platelet function

Eligibility criteria: 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)

Primary outcomes:
measure: Platelet function as assessed by a CPA system
timeFrame: 6 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Tel Aviv Medical Center
Study officials:
affiliation: Tel Aviv Medical Center, Israel
name: Shmuel Banai, MD
role: STUDY_CHAIR
References:
citation: 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.