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

NCT00950339 | Completed Phase 4

• 1 other identifier: TASMC-09-SB-0196-09-TLV-CTIL
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

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.

Conditions

Coronary Heart Disease; GI Bleeding

Keywords

GI bleeding; clopidogrel; aspirin; prevention; angiography

Outcome Measures

Primary Outcomes (1)

• Platelet function as assessed by a CPA system

  6 weeks

Study Arms (3)

4 weeks of omeprazole, 20mg twice daily

EXPERIMENTAL

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

Drug: omeprazole, 20mg twice daily; Drug: famotidine 40mg twice daily; Drug: pantoprazole 40mg once daily

4 weeks of famotidine 40mg twice daily

EXPERIMENTAL

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

Drug: omeprazole, 20mg twice daily; Drug: famotidine 40mg twice daily; Drug: pantoprazole 40mg once daily

4 weeks of pantoprazole 40mg once daily

EXPERIMENTAL

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

Drug: omeprazole, 20mg twice daily; Drug: famotidine 40mg twice daily; Drug: pantoprazole 40mg once daily

Interventions

omeprazole, 20mg twice daily DRUG

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

Also known as: PPI Platelet Inhibitory

4 weeks of famotidine 40mg twice daily; 4 weeks of omeprazole, 20mg twice daily; 4 weeks of pantoprazole 40mg once daily

famotidine 40mg twice daily DRUG

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

Also known as: PPI Platelet Inhibitory

4 weeks of famotidine 40mg twice daily; 4 weeks of omeprazole, 20mg twice daily; 4 weeks of pantoprazole 40mg once daily

pantoprazole 40mg once daily DRUG

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

Also known as: PPI Platelet Inhibitory

4 weeks of famotidine 40mg twice daily; 4 weeks of omeprazole, 20mg twice daily; 4 weeks of pantoprazole 40mg once daily

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Known allergy to PPI of H2 blockers
• Known thrombocytopenia or thrombocytopathia
• 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.
• Subject with symptomatic heart failure of LVEF ≤ 25%
• Acute myocardial infarction within the past 30 days.
• No acute inflammatory event during the past month (e.g. infection, autoimmune or acute coronary event)
• Concurrent medical condition with a life expectancy of less than 12 months.
• Known severe renal failure (serum creatinine level \>2.5 mg/dl).
• History of bleeding diathesis or coagulopathy or inability or unwillingness to receive blood transfusions.
• Evidence of active gastrointestinal bleeding or a history of such bleeding that is not known to have been treated and proven to have resolved.
• History of hepatitis (viral, ischemic or chemically-induced); clinical jaundice, history of cirrhosis.
• Patient treated with anticoagulant medication (Coumadin, LMWH)

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead
• Tel Aviv Medical Center: collaborator

Study Sites (1)

Tel Aviv Medical Center

Tel Aviv, Israel

Location

Related Publications (1)

• 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.

  PMID: 23630016 DERIVED

MeSH Terms

Conditions

Coronary Disease; Gastrointestinal Hemorrhage

Interventions

Omeprazole; Famotidine; Pantoprazole

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Gastrointestinal Diseases; Digestive System Diseases; Hemorrhage; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Thiazoles; Azoles

Study Officials

• Shmuel Banai, MD

  Tel Aviv Medical Center, Israel

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Interventional cardiologist

Study Record Dates

• First Submitted: April 19, 2009
• First Posted: July 31, 2009
• Study Start: August 1, 2009
• Primary Completion: June 1, 2011
• Study Completion: August 1, 2011
• Last Updated: July 7, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)