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Completed

NCT Number: NCT01896557

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.

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Key information

Conditions

Coronary Artery Disease Arterial Occlusive Diseases Arteriosclerosis Cardiovascular Diseases Coronary Disease Drug Interaction Potentiation Heart Diseases Myocardial Ischemia Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Omeprazole

Drug

Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.

Other names: Peprazol, Losec, PPI

Ranitidine

Drug

Influence of ranitidine on clopidogrel pharmacodynamics will be evaluated.

Other names: Antak, H2 receptor blocker

clopidogrel

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

Other names: Plavix, ADP receptor blocker

Primary outcomes

  1. Comparing Platelet Function of Patients on Dual Antiplatelet Therapy With ASA + Clopidogrel, Between the Groups Ranitidin and Omeprazole, After One Week of Randomized Treatment

    Time frame: 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.

  2. Comparing Platelet Function of Patients on Dual Antiplatelet Therapy With ASA + Clopidogrel, Between the Groups Ranitidin and Omeprazole, Using VerifyNow Method.

    Time frame: 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.

Other outcomes

  1. Comparison of the Primary Outcome With Bioimpedance Aggregometry

    Time frame: 1 week after drug exposure

    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

  2. Comparing the Main Outcome on Pre-specified Subgroups

    Time frame: 1 week after drug exposure

    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.

  3. Comparison of the Primary Outcome With PFA-100 (Collagen/ADP Cartridge)

    Time frame: 1 week after drug exposure

    After 1 week of randomization to ranitidin or omeprazole, the platelet function will also be analysed by other method: PFA-100(Collagen/ADP cartridge).

Sponsors and collaborators

Lead sponsor

University of Sao Paulo General Hospital

Other

Collaborators

  • InCor Heart Institute

Registry information

Official study title

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

Important dates

Study start
2011
Primary completion
2013
Study completion
2013
First posted
Jul 11, 2013
Registry last updated
Jul 6, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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