Ignite Creation Date:
2024-05-05 @ 10:03 PM
Last Modification Date:
2024-10-26 @ 10:13 AM
Study NCT ID:
NCT01016717
Status:
WITHDRAWN
Last Update Posted:
2016-10-21
First Post:
2009-11-18
Brief Title:
Clopidogrel Proton-Pump Inhibitors Study
Sponsor:
Sheba Medical Center
Organization:
Sheba Medical Center
Study Overview
Official Title:
Clopidogrel Proton-Pump Inhibitors Study
Status:
WITHDRAWN
Status Verified Date:
2016-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Since the published data resolved the study goals we decided not to start it
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
Detailed Description:
On June 19 2009 The European Medicines Agency EMEA has issued a public statement on a possible interaction between clopidogrel Plavix Sanofi-AventisBristol-Myers Squibband 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 mgday Abic Inc Israel or pantoprazole tables Controloc 40 40 mgday Nycomed Perrigo Inc Israel for 1 month Phase 1 followed by a 4-week washout period and the alternative treatment for 1 month Phase 2Platelet 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 3000min 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
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 mgday Abic Inc Israel or pantoprazole tables Controloc 40 40 mgday Nycomed Perrigo Inc Israel for 1 month Phase 1 followed by a 4-week washout period and the alternative treatment for 1 month Phase 2Platelet 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 3000min 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None