Coronary Artery DiseasePhase 4NCT01896557
Ranitidin Versus Omeprazole in Patients Taking Clopidogrel
A Phase 4 study testing omeprazole, Ranitidine and Clopidogrel in people with Coronary Artery Disease and Drug Interaction Potentiation, run by University of Sao Paulo General Hospital.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Drug Interaction Potentiation
- What is being tested?
- omeprazole, Ranitidine and Clopidogrel
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- No sites listed yet
- Study dates
- Oct 2011to Jun 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
About this study
Official title: Possible Drug Interaction Between Clopidogrel and Ranitidin or Omeprazole in Patients With Stable Coronary Heart Disease: a Comparative Study
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.
Read the 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.
- Being tested
- omeprazole, Ranitidine, Clopidogrel
- Keywords
- clopidogrel, omeprazole, ranitidin, interaction, aggregability
- Medical subject headings
- Coronary Artery Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
omeprazoleDrug
Also called Peprazol, Losec, PPI
Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated.
RanitidineDrug
Also called Antak, H2 receptor blocker
Influence of ranitidine on clopidogrel pharmacodynamics will be evaluated.
ClopidogrelDrug
Also called Plavix, ADP receptor blocker
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: omeprazole; Drug: Clopidogrel |
| ranitidine | Experimental | Ranitidine 150 mg (oral route) twice a day will be given to the subjects for one week. Receives: Drug: Ranitidine; Drug: Clopidogrel |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: One week after drug exposure (omeprazole/ranitidine); 2 weeks after baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2013 (estimated)
- Study startOct 2011
- Primary completionJun 2013
- Study completionJun 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- More trials run by University of Sao Paulo General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 92 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- InCor Heart Institute
- Responsible party
- Sponsor
- Investigators
- José C Nicolau, Professor, Principal investigator, Director of Acute Coronary Care Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01896557
- Sponsor's protocol ID
- 0136/11
- Status last verified
- Oct 2011
- First submitted
- 19 Jun 2013
- Last updated
- 6 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 27289472
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Possible Drug Interaction Between Clopidogrel and Ranitidin or Omeprazole in Patients With Stable Coronary Heart Disease: a Comparative Study
- ClinicalTrials.gov ID
- NCT01896557
- Acronym / sponsor ID
- 0136/11
- Keywords
- clopidogrel, omeprazole, ranitidin, interaction, aggregability
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 92 participants (actual)
- Lead sponsor
- University of Sao Paulo General HospitalUniversity, hospital or other
- Collaborators
- InCor Heart Institute
- Study start
- Oct 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 11 Jul 2013 (estimated)
- Results
- Posted 23 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| omeprazole | Experimental | Drug: omeprazole, Drug: ClopidogrelOmeprazole 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. |
| ranitidine | Experimental | Drug: Ranitidine, Drug: ClopidogrelRanitidine 150 mg (oral route) twice a day will be given to the subjects for one week. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| omeprazoleAlso: Peprazol, Losec, PPIInfluence of omeprazole on clopidogrel pharmacodynamics will be evaluated. | Drug | omeprazole |
| RanitidineAlso: Antak, H2 receptor blockerInfluence of ranitidine on clopidogrel pharmacodynamics will be evaluated. | Drug | ranitidine |
| ClopidogrelAlso: Plavix, ADP receptor blockerClopidogrel 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 | Drug | omeprazole, ranitidine |
Primary outcome
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27289472Furtado 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
José C Nicolau, Professor principal investigator
Director of Acute Coronary Care Unit
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing omeprazole, Ranitidine and Clopidogrel in people with Coronary Artery Disease and Drug Interaction Potentiation, run by University of Sao Paulo General Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01896557, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2018; AzTrials last refreshed its copy on 6 Nov 2026.