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
|Official Title:||Clopidogrel Proton-Pump Inhibitors Study|
- Platelet function tests. [ Time Frame: 30 days ] [ Designated as safety issue: No ]
|Study Start Date:||December 2012|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Active Comparator: Omeprazole
Patients will be taking omeprazole tablets 40 mg QD for 30 days
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
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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01016717
|Leviev Heart Center, Sheba Medical Center|
|Tel Hashomer, Israel, 52621|
|Principal Investigator:||Michael Shechter, MD, MA||Leviev Heart Center, Sheba Medical Center, Tel Hashomer|