PPI and Clopidogrel Response | RxWiki

PPI and Clopidogrel Response

Overview[ - collapse ][ - ]

Purpose	Clopidogrel, in combination with aspirin, is currently the recommended treatment for secondary prevention of ischemic events in high-risk patients and for prevention of coronary artery stent thrombosis. Patients receiving aspirin and clopidogrel are frequently treated with proton pump inhibitors, such as omeprazole or pantoprazole, in order to prevent the risk of gastrointestinal bleeding, accorded to guidelines. An interaction between proton pump inhibitors and clopidogrel has been suggested, which may lead to a decrease of clopidogrel effects. It remains unclear whether this interaction between PPIs and clopidogrel might be a class effect or if this may be affected by timing regimen. The objectives of this two-phase investigation are: 1. to compare clopidogrel platelet inhibitory effects when taken at the same time versus separated at least 8 hours from omeprazole administration. 2. to compare clopidogrel-induced inhibitory effects when taken at the same time versus staggered at least 8 hours from pantoprazole administration.
Condition	Drug Interaction
Intervention	Drug: omeprazole and pantoprazole
Phase	Phase 1
Sponsor	University of Florida
Responsible Party	University of Florida
ClinicalTrials.gov Identifier	NCT01170533
First Received	July 23, 2010
Last Updated	March 5, 2012
Last verified	March 2012

Tracking Information[ + expand ][ + ]

First Received Date	July 23, 2010
Last Updated Date	March 5, 2012
Start Date	March 2009
Estimated Primary Completion Date	August 2010
Current Primary Outcome Measures	Platelet Function as Assessed by the P2Y12 Reactivity Index [Time Frame: 1 week] [Designated as safety issue: No]P2Y12 reactivity index which will be assessed by flow cytometry determination of vasodilator-stimulated phosphoprotein (VASP).
Current Secondary Outcome Measures	Not Provided

Descriptive Information[ + expand ][ + ]

Brief Title	PPI and Clopidogrel Response
Official Title	Effects of PPI Therapy on Clopidogrel-Induced Antiplatelet Effects: A Randomized Study
Brief Summary	Clopidogrel, in combination with aspirin, is currently the recommended treatment for secondary prevention of ischemic events in high-risk patients and for prevention of coronary artery stent thrombosis. Patients receiving aspirin and clopidogrel are frequently treated with proton pump inhibitors, such as omeprazole or pantoprazole, in order to prevent the risk of gastrointestinal bleeding, accorded to guidelines. An interaction between proton pump inhibitors and clopidogrel has been suggested, which may lead to a decrease of clopidogrel effects. It remains unclear whether this interaction between PPIs and clopidogrel might be a class effect or if this may be affected by timing regimen. The objectives of this two-phase investigation are: 1. to compare clopidogrel platelet inhibitory effects when taken at the same time versus separated at least 8 hours from omeprazole administration. 2. to compare clopidogrel-induced inhibitory effects when taken at the same time versus staggered at least 8 hours from pantoprazole administration.
Detailed Description	Clopidogrel, in combination with aspirin, is currently the recommended treatment for secondary prevention of ischemic events in high-risk patients and for prevention of coronary artery stent thrombosis. Patients receiving aspirin and clopidogrel are frequently treated with proton pump inhibitors, such as omeprazole or pantoprazole, in order to prevent the risk of gastrointestinal bleeding, accorded to guidelines. An interaction between proton pump inhibitors and clopidogrel has been suggested, which may lead to a decrease of clopidogrel effects. It remains unclear whether this interaction between PPIs and clopidogrel might be a class effect or if this may be affected by timing regimen. The objectives of this two-phase investigation are: 1. to compare clopidogrel platelet inhibitory effects when taken at the same time versus separated at least 8 hours from omeprazole administration. 2. to compare clopidogrel-induced inhibitory effects when taken at the same time versus staggered at least 8 hours from pantoprazole administration. The clopidogrel dose will be a 600mg loading dose followed by a 75mg daily maintenance dose, starting the next day for 7 days. Omeprazole will be used at a daily dose of 40mg and pantoprazole at 80mg. The proposed study will have a prospective, randomized, cross-over design. Subjects are randomized in a 1:1 fashion to take PPI concomitantly (CONC regimen) or staggered by 8-12 hours (STAG regimen) for one-week on a background of clopidogrel therapy. In particular, in the CONC regimen both drugs were taken in the morning, while in the STAG regimen clopidogrel was taken in the morning and omeprazole in the evening. After a 2-4 week washout period, subjects crossed-over treatment regimen. After completing these two treatment phases, subjects underwent another washout period of 2-4 weeks and were treated for 1 week with clopidogrel alone, without receiving omeprazole therapy (CLOP regimen). The sequence with the PPI pantoprazole will have the same prospective, randomized, cross-over design as the omeprazole sequence. A CLOP regimen in the absence of pantoprazole will be collected before entering randomization phase with adequate wash-out period. Blood sampling for platelet function assessments were performed at all three phases of the study at the following time points: a) baseline, b) 24 hours after LD (before intake of study medication), and c) 7 days (24 hours after the last MD).
Study Type	Interventional
Study Phase	Phase 1
Study Design	Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Open Label
Condition	Drug Interaction
Intervention	Drug: omeprazole and pantoprazole The clopidogrel dose will be a 600mg loading dose followed by a 75mg daily maintenance dose, starting the next day for 7 days. Omeprazole will be used at a daily dose of 40mg and pantoprazole at 80mg.
Study Arm (s)	Active Comparator: Omeprazole prospective, open-label, two-sequence, three-period, randomized crossover study Active Comparator: Pantoprazole prospective, open-label, two-sequence, three-period, randomized crossover study

Recruitment Information[ + expand ][ + ]

Recruitment Status	Completed
Estimated Enrollment	20
Estimated Completion Date	August 2010
Estimated Primary Completion Date	August 2010
Eligibility Criteria	Inclusion Criteria: - Healthy volunteers aged between 18 and 75 years Exclusion Criteria: 1. Known allergies to clopidogrel or omeprazole. 2. Blood dyscrasia or bleeding diathesis. 3. Recent antiplatelet treatment (< 30 days) with a glycoprotein IIb/IIIa antagonist, thienopyridine (ticlopidine, clopidogrel), cilostazol or dipyridamole. 4. Treatment with other medications that may interfere with the CYP system (ketoconazole, itraconazole, diltiazem, erythromycin, clarithromycin, fluvoxamine, fluoxetine, nefazodone, or sertraline). 5. Platelet count <100x106/microL. 6. Diabetes mellitus 7. History of coronary artery disease, gastrointestinal bleed, gastroesophageal reflux disease (GERD), cerebrovascular event or any active malignancy. 8. Active bleeding or hemodynamic instability. 9. Serum creatinine >2mg/dL. 10. Baseline ALT >2.5 times the upper limit of normal. 11. Pregnant females. 12. Patients taking omeprazole or any H2 antagonist or proton pump inhibitors
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	Accepts Healthy Volunteers
Contacts	Not Provided
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01170533
Other Study ID Numbers	UFJ 2009-2
Has Data Monitoring Committee	Yes
Information Provided By	University of Florida
Study Sponsor	University of Florida
Collaborators	Bristol-Myers Squibb Sanofi
Investigators	Principal Investigator: Dominick J Angiolillo, MD, PhD University of Florida
Verification Date	March 2012

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