Ranitidin Versus Omeprazole in Patients Taking Clopidogrel

Coronary Artery Disease Clinical Trial

Official title:

Possible Drug Interaction Between Clopidogrel and Ranitidin or Omeprazole in Patients With Stable Coronary Heart Disease: a Comparative Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01896557
• Other study ID #: 0136/11
• Status: Completed
• Phase: Phase 4
• Start date: October 2011
• Est. completion date: June 2013

Study information

• Verified date: October 2011
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Drug Interaction Potentiation
• Myocardial Ischemia

Intervention

Drug:
• omeprazole
Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.
• Ranitidine
Influence of ranitidine on clopidogrel pharmacodynamics will be evaluated.
• 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

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital	InCor Heart Institute

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Comparison of the Primary Outcome With Bioimpedance Aggregometry	After 1 week of randomization to ranitidin or omeprazole, the platelet function will also be analysed by other method: bioimpedance aggregometry with ADP 10 mcM as reagent	1 week after drug exposure
Other	Comparing the Main Outcome on Pre-specified Subgroups	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.	1 week after drug exposure
Other	Comparison of the Primary Outcome With PFA-100 (Collagen/ADP Cartridge)	After 1 week of randomization to ranitidin or omeprazole, the platelet function will also be analysed by other method: PFA-100(Collagen/ADP cartridge).	1 week after drug exposure
Primary	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 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.	One week after randomized treatment exposure (omeprazole or ranitidine)
Primary	Comparing Platelet Function of Patients on Dual Antiplatelet Therapy With ASA + Clopidogrel, Between the Groups Ranitidin and Omeprazole, Using VerifyNow Method.	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.	One week after drug exposure (omeprazole/ranitidine); 2 weeks after baseline