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

Coronary Heart Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00950339
• Other study ID #: TASMC-09-SB-0196-09-TLV-CTIL
• Status: Completed
• Phase: Phase 4
• First received: April 19, 2009
• Last updated: July 6, 2016
• Start date: August 2009
• Est. completion date: August 2011

Study information

• Verified date: July 2016
• Source: Tel-Aviv Sourasky Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: August 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Gastrointestinal Hemorrhage
• GI Bleeding
• Heart Diseases
• Hemorrhage
• Myocardial Ischemia

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Israel	Tel Aviv Medical Center	Tel Aviv

Sponsors (2)

Lead Sponsor	Collaborator
Tel-Aviv Sourasky Medical Center	Tel Aviv Medical Center

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Platelet function as assessed by a CPA system		6 weeks	No