Ranitidin Versus Omeprazole in Patients Taking Clopidogrel

NCT01896557 | Completed Phase 4 Results DMC

• 1 other identifier: 0136/11
• Study Type: interventional
• Target: 92
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Coronary Artery Disease; Drug Interaction Potentiation

Keywords

clopidogrel; omeprazole; ranitidin; interaction; aggregability

Outcome Measures

Primary Outcomes (2)

• 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)

• 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

Other Outcomes (3)

• Comparison of the Primary Outcome With Bioimpedance Aggregometry

  1 week after drug exposure

• Comparing the Main Outcome on Pre-specified Subgroups

  1 week after drug exposure

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

  1 week after drug exposure

Study Arms (2)

omeprazole

EXPERIMENTAL

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; Drug: Clopidogrel

ranitidine

EXPERIMENTAL

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

Drug: Ranitidine; Drug: Clopidogrel

Interventions

omeprazole DRUG

Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.

Also known as: Peprazol, Losec, PPI

omeprazole

Ranitidine DRUG

Influence of ranitidine on clopidogrel pharmacodynamics will be evaluated.

Also known as: Antak, H2 receptor blocker

ranitidine

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

Also known as: Plavix, ADP receptor blocker

omeprazole; ranitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Sao Paulo General Hospital: lead
• InCor Heart Institute: collaborator

Related Publications (1)

• 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.

  PMID: 27289472 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Omeprazole; Ranitidine; Clopidogrel; Purinergic P2Y Receptor Antagonists

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Furans; Ticlopidine; Thienopyridines; Thiophenes; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Physiological Effects of Drugs

Results Point of Contact

• Title: Remo Holanda de Mendonca Furtado
• Organization: Heart Institute of University of Sao Paulo Medical School

remo_holanda@hotmail.com

+5511 26615058

Study Officials

• José C Nicolau, Professor

  Director of Acute Coronary Care Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2013
• First Posted: July 11, 2013
• Study Start: October 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: July 6, 2018
• Results First Posted: May 23, 2016

Record last verified: 2011-10