Ranitidin Versus Omeprazole in Patients Taking Clopidogrel
Previous reports have shown a possible drug interaction between clopidogrel and proton pump inhibitors (PPI´s), which could result in increased number of adverse cardiovascular events among patients on dual antiplatelet therapy(DAPT). Because of this, ranitidin has been proposed as an alternative drug to PPI´s for prophylaxis of gastrointestinal bleeding in patients who need DAPT. The study´s aim is to test the hypothesis that ranitidin doesn´t have any influence on clopidogrel pharmacodynamic.
|Study Design:||Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Possible Drug Interaction Between Clopidogrel and Ranitidin or Omeprazole in Patients With Stable Coronary Heart Disease: a Comparative Study|
- Comparing platelet function of patients on dual antiplatelet therapy with ASA + clopidogrel, between the groups ranitidin and omeprazole, using VerifyNow method. [ Time Frame: 1 week after drug exposure ] [ Designated as safety issue: No ]One week after starting double-blind, double-dummy, randomized therapy with ranitidin or omeprazole on patients treated with DAPT, platelet function will be compared with the method VerifyNow.
- Comparison of the primary outcome with other two methods of platelet aggregability: PFA-100 and bioimpedance aggregometry [ Time Frame: 1 week after drug exposure ] [ Designated as safety issue: No ]After 1 week of randomization to ranitidin or omeprazole, the platelet function will also be analysed by two other methods: PFA-100 (Siemens-USA) and bioimpedance aggregometry.
- Comparing the main outcome on pre-specified subgroups [ Time Frame: 1 week after drug exposure ] [ Designated as safety issue: No ]
The main outcome will be compared on pre-specified subgroups:
- elderly (age > 65 yrs-old) versus non-elderly
- male versus female
- smoking versus non-smoking patients
- obese (BMI > 30 kg/m2) versus non-obese
- diabetic versus non-diabetic
- patients in use or not in use of statins
- presence or not of genetic polymorphisms on cytochrome 2C19.
|Study Start Date:||October 2011|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Omeprazole 20 mg (oral route) twice a day will be given to the subjects for one week. This intervention will be compared with ranitidin 150 mg (oral route) twice a day.
Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.
Study population: 100 patients with Stable Coronary Artery Disease from Heart Institute
- Age > 18 years old
- Coronary artery disease, defined as previous myocardial infarction and/or coronary angioplasty and/or Coronary Artery Bypass Graft (CABG) surgery and/or coronariography showing obstruction of at least 50 % in one of major epicardial vessels
- Treatment with Acetylsalicylic Acid (ASA) 100 mg/day
- Use in the last 7 days of oral anticoagulant or any other antiplatelet drug beside ASA
- Previous utilization of PPI or ranitidine in the last 7 days before randomization
- Active bleeding
- Pregnancy or woman of childbearing age without contraceptive method
- Hemoglobin < 10 g/dL or hematocrit < 30 %, hematocrit > 50 %, platelets < 100.000/mm3 or > 500.000/mm3; creatinin clearance < 50 ml/minute
- Percutaneous coronary intervention (PCI) on the last 30 days before randomization (or PCI on the last year when drug-eluted stents are used); CABG surgery on the last 90 days; acute coronary syndrome on the last 60 days
- Active malignant neoplasm
- Active peptic ulcer disease on the last 60 days or upper gastrointestinal bleeding any time in life
- Known allergy to the drugs clopidogrel, ranitidine or omeprazole
- Refuse to participate in the study]
Methodology: The study has a double-blind, double-dummy prospective design. Clopidogrel action is evaluated by platelet function tests: VerifyNow, bioimpedance aggregometry and Platelet Function Analyzer-100 (PFA-100). The patients have measurements of platelet function on three moments: before starting clopidogrel; 1 week after DAPT with clopidogrel (without loading dose) plus ASA; and after 1 week of randomization to ranitidin 150 mg bid or omeprazole 20 mg bid.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01896557
|Principal Investigator:||José C Nicolau, Professor||Director of Acute Coronary Care Unit|