Ranitidin Versus Omeprazole in Patients Taking Clopidogrel

Phase 4

Completed

Conditions: Drug Interaction Potentiation
Coronary Artery Disease

Interventions: Drug: omeprazole
Drug: Ranitidine
Drug: Clopidogrel

Registration Number: NCT01896557

Lead Sponsor: University of Sao Paulo General Hospital

Brief Summary: 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.

Detailed Description: Study population: 100 patients with Stable Coronary Artery Disease from Heart Institute

Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 92

Inclusion Criteria

Age > 18 years old
Coronary artery disease, defined as previous myocardial infarction and/or coronary angioplasty and/or 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

Exclusion Criteria

Use on the last 7 days of any other antiplatelet drug beside ASA or oral anticoagulant
Previous utilization of PPI or ranitidine in the last 7 days before randomization
Any 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ranitidine	Clopidogrel	Ranitidine 150 mg (oral route) twice a day will be given to the subjects for one week.
omeprazole	omeprazole	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.
ranitidine	Ranitidine	Ranitidine 150 mg (oral route) twice a day will be given to the subjects for one week.
omeprazole	Clopidogrel	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.

Primary Outcome Measures

Name	Time	Method
Comparing Platelet Function of Patients on Dual Antiplatelet Therapy With ASA + Clopidogrel, Between the Groups Ranitidin and Omeprazole, After One Week of Randomized Treatment	One week after randomized treatment exposure (omeprazole or ranitidine)	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, in P2Y12 Reactivity Units.
Comparing Platelet Function of Patients on Dual Antiplatelet Therapy With ASA + Clopidogrel, Between the Groups Ranitidin and Omeprazole, Using VerifyNow Method.	One week after drug exposure (omeprazole/ranitidine); 2 weeks after baseline	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, in percent Inhibition of Platelet Aggregation (IPA) from baseline. IPA was calculated as the percent change in aggregability from baseline, with the formula IPA = (on-treatment aggregability minus baseline aggregability)/baseline aggregability. Since baseline aggregation is always, per definition, equal or more than on-treatment aggregation, there is no possibility that this number might be negative.

Secondary Outcome Measures