Clopidogrel Proton-Pump Inhibitors Study
Information source: Sheba Medical Center
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Coronary Artery Disease
Intervention: Omeprazole (Drug); Pantoprazole (Drug)
Phase: Phase 4
Status: Suspended
Sponsored by: Sheba Medical Center Official(s) and/or principal investigator(s): Michael Shechter, MD, MA, Principal Investigator, Affiliation: Leviev Heart Center, Sheba Medical Center, Tel Hashomer
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.
Clinical Details
Official title: Clopidogrel Proton-Pump Inhibitors Study
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Primary outcome: Platelet function tests.
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 80 Years.
Gender(s): Both.
Criteria:
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.
Locations and Contacts
Leviev Heart Center, Sheba Medical Center, Tel Hashomer 52621, Israel
Additional Information
Leviev Heart Center and the Clinical Research Unit
Starting date: December 2012
Last updated: June 14, 2012
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