Ranitidin Versus Omeprazole in Patients Taking Clopidogrel

NCT ID: NCT01896557

Last Updated: 2018-07-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2013-06-30

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.

Conditions

Coronary Artery Disease; Drug Interaction Potentiation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

omeprazole

Intervention Type: DRUG

Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.

Clopidogrel

Intervention Type: DRUG

Clopidogrel added to ASA therapy at the first medical visit, Open label 75 mg once a day will be given to all individuals as part of the protocol (since main outcome of interest is clopidogrel effect. Actual comparison arms are double blind ranitidine and omeprazole

ranitidine

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

Group Type: EXPERIMENTAL

Ranitidine

Intervention Type: DRUG

Influence of ranitidine on clopidogrel pharmacodynamics will be evaluated.

Clopidogrel

Intervention Type: DRUG

Clopidogrel added to ASA therapy at the first medical visit, Open label 75 mg once a day will be given to all individuals as part of the protocol (since main outcome of interest is clopidogrel effect. Actual comparison arms are double blind ranitidine and omeprazole

Interventions

omeprazole

Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.

Intervention Type: DRUG

Ranitidine

Influence of ranitidine on clopidogrel pharmacodynamics will be evaluated.

Intervention Type: DRUG

Clopidogrel

Clopidogrel added to ASA therapy at the first medical visit, Open label 75 mg once a day will be given to all individuals as part of the protocol (since main outcome of interest is clopidogrel effect. Actual comparison arms are double blind ranitidine and omeprazole

Intervention Type: DRUG

Other Intervention Names

Peprazol; Losec; PPI; Antak; H2 receptor blocker; Plavix; ADP receptor blocker

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

InCor Heart Institute

OTHER

Sponsor Role: collaborator

University of Sao Paulo General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

José C Nicolau, Professor

Role: PRINCIPAL_INVESTIGATOR

Director of Acute Coronary Care Unit

References

Furtado RHM, Giugliano RP, Strunz CMC, Filho CC, Ramires JAF, Filho RK, Neto PAL, Pereira AC, Rocha TR, Freire BT, D'Amico EA, Nicolau JC. Drug Interaction Between Clopidogrel and Ranitidine or Omeprazole in Stable Coronary Artery Disease: A Double-Blind, Double Dummy, Randomized Study. Am J Cardiovasc Drugs. 2016 Aug;16(4):275-284. doi: 10.1007/s40256-016-0172-5.

Reference Type: DERIVED

PMID: 27289472 (View on PubMed)

Other Identifiers

0136/11

Identifier Type: -

Identifier Source: org_study_id