Ranitidin Versus Omeprazole in Patients Taking Clopidogrel

University of Sao Paulo General Hospital

Status and phase: Completed; Phase 4

Conditions: Coronary Artery Disease; Drug Interaction Potentiation

Treatments: Drug: Clopidogrel; Drug: omeprazole; Drug: Ranitidine

Study type: Interventional

Funder types: Other

Identifiers

NCT01896557

0136/11

Details and patient eligibility

About

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.

Full 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.

Enrollment: 92 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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92 participants in 2 patient groups

omeprazole

Experimental group

Description:

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.

Treatment:

Drug: omeprazole

Drug: Clopidogrel

ranitidine

Experimental group

Description:

Ranitidine 150 mg (oral route) twice a day will be given to the subjects for one week.

Treatment:

Drug: Ranitidine

Drug: Clopidogrel