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Clopidogrel Proton-Pump Inhibitors Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01016717
Recruitment Status : Withdrawn (Since the published data resolved the study goals we decided not to start it)
First Posted : November 19, 2009
Last Update Posted : October 21, 2016
Information provided by (Responsible Party):
Sheba Medical Center

Brief Summary:
To find out the impact of two different proton-pump inhibitors (PPIs) (Omeprazole and Pantoprazole) on platelet function in patients with stable coronary artery disease (CAD) on clopidogrel therapy.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Drug: Omeprazole Drug: Pantoprazole Phase 4

Detailed Description:

On June 19, 2009 The European Medicines Agency (EMEA) has issued a public statement on a possible interaction between clopidogrel (Plavix, Sanofi-Aventis/Bristol-Myers Squibb)and proton-pump inhibitors (PPIs) and has recommended that the product information for all clopidogrel-containing medicines be amended to discourage concomitant use of PPIs unless absolutely necessary. The UK medicines regulator, the Medicines and Healthcare Products Regulatory Agency (MHRA), has also issued advice to GPs that concomitant use of a PPI with clopidogrel is not recommended unless considered essential, urging a review of the prescribing of PPIs at the next appointment for patients taking clopidogrel. This follows an "early communication" issued by the US FDA earlier this year, stating that PPIs might interfere with the effectiveness of clopidogrel and that clinicians should reevaluate starting or continuing treatment with a PPI in patients taking clopidogrel.

There is a concern that the studies on which these warnings are based have many limitations and that it is far from certain whether there really is an interaction between clopidogrel and PPIs.

Another point of uncertainty is whether there may be a difference between individual PPIs, with some pharmacodynamic studies suggesting an interaction with omeprazole but not with pantoprazole. The clinical evidence, however, is conflicting. There has been one clinical trial from Canada suggesting an interaction with omeprazole but not with pantoprazole. From a mechanistic view it is known that omeprazole is metabolized by the CYP219 enzyme, which converts clopidogrel into its active metabolite. And while pantoprazole can also be metabolized by this enzyme, it also uses other routes.

Thus, the primary goal of the current study is to find out the impact of two different PPIs (Omeprazole, Losec, and Pantoprazole) on platelet function in patients with stable coronary artery disease (CAD) on clopidogrel therapy.

Forty patients with stable CAD will be randomized to receive either omeprazole tables (Losec, 40 mg/day, Abic Inc., Israel) or pantoprazole tables (Controloc 40, 40 mg/day, Nycomed, Perrigo Inc., Israel) for 1 month (Phase 1), followed by a 4-week washout period, and the alternative treatment for 1 month (Phase 2).Platelet function tests will be assessed 4 times: before and after each study phase. Following an overnight fast, ECG and blood tests for measurements of platelet function, lipids, blood cell count, electrolytes, fasting glucose, and high-sensitivity C-reactive protein (hs-CRP), will be performed. The blood samples, except those for platelet function, will be centrifuged immediately for 15 minutes at 3000/min. The sera will be stored at -20° C, and will be tested at the end of the study. Blood samples for platelet function will be assessed immediately after the blood is drawn. All blood samples will be evaluated in the same laboratory and by the same operator who will be blinded to the patients' clinical status and PPIs allocation.

All patients will be instructed to continue taking their regular medications throughout the study period. In addition, patients will be instructed not to add any medications (including over the counter medications) and to record any change in concomitant medications throughout the study period.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Clopidogrel Proton-Pump Inhibitors Study
Study Start Date : December 2012
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Omeprazole
Patients will be taking omeprazole tablets 40 mg QD for 30 days
Drug: Omeprazole
All patients will be taking omeprazole (Losec, Abic Inc., Israel) tablets 40 mg QD for 30 days
Other Name: Losec

Active Comparator: Pantoprazole
Patients will be taking Pantoprazole tablets 40 mg QD for 30 days
Drug: Pantoprazole
Pantoprazole tablets (Controloc 40, 40 mg/day, Nycomed, Perrigo Inc., Israel). All patients will take pantoprazole tablets 40 mg QD for 30 days
Other Name: Controloc

Primary Outcome Measures :
  1. Platelet function tests. [ Time Frame: 30 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Male or female ≥ 18 years; signed informed consent
  2. Outpatient CAD patients on aspirin tablets 100-325 mg daily and clopidogrel tablets 75 mg daily.
  3. Left ventricular (LV) systolic dysfunction ≥ 40% measured within the past 6 months.
  4. No changes in cardiac medications during 2 weeks prior to enrollment.

Exclusion criteria:

  1. Presence of transplanted tissue or organ or LVAD
  2. AICD or CRT or CRTD patients.
  3. Acute MI, CABG, PCI within past 3 months.
  4. Congestive heart failure (CHF) ≥ NYHA 2.
  5. Ejection fraction < 40% measured within the past 6 months.
  6. Malignancy.
  7. Active myocarditis, or cardiomyopathy.
  8. HIV infection or immunodeficiency state.
  9. Chronic viral infection.
  10. Acute systemic infection requiring antibiotics.
  11. Chronic diarrhea or malabsorption.
  12. Statin therapy initiation ≤ 3 months.
  13. Diabetes mellitus type 1.
  14. Diabetes mellitus type 2 with HbA1C > 7%
  15. Low-density lipoprotein cholesterol (LDL-C) > 100 mg/dL.
  16. Not on statin therapy.
  17. Liver function tests (LFT) ≥ x 3 upper limit of normal (ULN) or creatinine kinase (CPK) ≥ x 10 ULN.
  18. Hypo/hyper thyroidism.
  19. Liver dysfunction.
  20. Renal failure with serum creatinine ≥ 2 mg/dL.
  21. Alcohol or drug abuse.
  22. Refuse to sign informed consent.
  23. On the following therapy: Amiodarone, coumadin, any antibiotics.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01016717

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Leviev Heart Center, Sheba Medical Center
Tel Hashomer, Israel, 52621
Sponsors and Collaborators
Sheba Medical Center
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Principal Investigator: Michael Shechter, MD, MA Leviev Heart Center, Sheba Medical Center, Tel Hashomer
Additional Information:
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Responsible Party: Sheba Medical Center Identifier: NCT01016717    
Other Study ID Numbers: SHEBA-09-7345-MS-CTIL
First Posted: November 19, 2009    Key Record Dates
Last Update Posted: October 21, 2016
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Sheba Medical Center:
platelet function
coronary disease
Additional relevant MeSH terms:
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Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Arterial Occlusive Diseases
Vascular Diseases
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action