Ranitidin Versus Omeprazole in Patients Taking Clopidogrel

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2011 by University of Sao Paulo General Hospital.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
InCor Heart Institute
Information provided by (Responsible Party):
University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier:
NCT01896557
First received: June 19, 2013
Last updated: July 10, 2013
Last verified: October 2011
  Purpose

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.


Condition Intervention Phase
VA Drug Interactions [VA Drug Interaction]
Drug: omeprazole
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Possible Drug Interaction Between Clopidogrel and Ranitidin or Omeprazole in Patients With Stable Coronary Heart Disease: a Comparative Study

Resource links provided by NLM:


Further study details as provided by University of Sao Paulo General Hospital:

Primary Outcome Measures:
  • Comparing platelet function of patients on dual antiplatelet therapy with ASA + clopidogrel, between the groups ranitidin and omeprazole, using VerifyNow method. [ Time Frame: 1 week after drug exposure ] [ Designated as safety issue: No ]
    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(Accumetrics - USA).


Secondary Outcome Measures:
  • Comparison of the primary outcome with other two methods of platelet aggregability: PFA-100 and bioimpedance aggregometry [ Time Frame: 1 week after drug exposure ] [ Designated as safety issue: No ]
    After 1 week of randomization to ranitidin or omeprazole, the platelet function will also be analysed by two other methods: PFA-100 (Siemens-USA) and bioimpedance aggregometry.


Other Outcome Measures:
  • Comparing the main outcome on pre-specified subgroups [ Time Frame: 1 week after drug exposure ] [ Designated as safety issue: No ]

    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 CYP2C19.


Enrollment: 100
Study Start Date: October 2011
Estimated Study Completion Date: August 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: omeprazole
Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.
Other Names:
  • Peprazol
  • Losec
  • PPI

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 CABG surgery and/or coronariography showing obstruction of at least 50 % in one of major epicardial vesses
  • 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 coronay 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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 vesses
  • 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 coronay 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01896557

Sponsors and Collaborators
University of Sao Paulo General Hospital
InCor Heart Institute
Investigators
Principal Investigator: José C Nicolau, Professor Director of Acute Coronary Care Unit
  More Information

No publications provided

Responsible Party: University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier: NCT01896557     History of Changes
Other Study ID Numbers: 0136/11
Study First Received: June 19, 2013
Last Updated: July 10, 2013
Health Authority: Brazil: National Committee of Ethics in Research

Keywords provided by University of Sao Paulo General Hospital:
clopidogrel
omeprazole
ranitidin
interaction
aggregability

Additional relevant MeSH terms:
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Omeprazole
Ranitidine
Ranitidine bismuth citrate
Clopidogrel
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Hematologic Agents
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents

ClinicalTrials.gov processed this record on July 23, 2014