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| Name | Class |
|---|---|
| InCor Heart Institute | OTHER |
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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.
Study population: 100 patients with Stable Coronary Artery Disease from Heart Institute
Inclusion Criteria:
Exclusion Criteria:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| ranitidine | Experimental | Ranitidine 150 mg (oral route) twice a day will be given to the subjects for one week. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| omeprazole | Drug | Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Comparing the Main Outcome on Pre-specified Subgroups |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| José C Nicolau, Professor | Director of Acute Coronary Care Unit | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27289472 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated. |
| FG001 | Ranitidine | Ranitidine 150 mg BID oral route was added to clopidogrel. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clopidogrel Alone |
|
| ||||||||||||||||||
| Clopidogrel + GI Protector |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated. |
| BG001 | Ranitidine |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Age according to categories (bellow versus more than or equal to 65 years-old) |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | P2Y12 Reactivity Units | One week after randomized treatment exposure (omeprazole or ranitidine) |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. omeprazole: Influence of omeprazole on clopidogrel pharmacodynamics will be evaluated. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspepsia | Gastrointestinal disorders | Non-systematic Assessment | Dyspepsia after clopidogrel was introduced without GI protector |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Remo Holanda de Mendonca Furtado | Heart Institute of University of Sao Paulo Medical School | +5511 26615058 | remo_holanda@hotmail.com |
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| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D009853 | Omeprazole |
| D011899 | Ranitidine |
| D000077144 | Clopidogrel |
| D058921 | Purinergic P2Y Receptor Antagonists |
| ID | Term |
|---|---|
| D053799 | 2-Pyridinylmethylsulfinylbenzimidazoles |
| D013454 | Sulfoxides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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| Ranitidine | Drug | Influence of ranitidine on clopidogrel pharmacodynamics will be evaluated. |
|
|
| 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 |
|
|
The main outcome will be compared on pre-specified subgroups:
|
| 1 week after drug exposure |
| 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 |
| NOT COMPLETED |
|
|
Ranitidine 150 mg BID oral route was added to clopidogrel. |
| BG002 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ranitidine |
Ranitidine 150 mg BID oral route was added to clopidogrel. |
|
|
| 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. | Posted | Mean | Standard Deviation | Percentage | One week after drug exposure (omeprazole/ranitidine); 2 weeks after baseline |
|
|
|
| Other Pre-specified | 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 | Platelet aggregation was measured after one week of randomized treatment therapy | Posted | Mean | Standard Deviation | Ohms | 1 week after drug exposure |
|
|
|
| Other Pre-specified | Comparing the Main Outcome on Pre-specified Subgroups | The main outcome will be compared on pre-specified subgroups:
| Not Posted | 1 week after drug exposure | Participants |
| Other Pre-specified | 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). | Platelet aggregation by PFA-100 was measured after one week of randomized treatment therapy | Posted | Mean | Standard Deviation | seconds | 1 week after drug exposure |
|
|
|
| 0 |
| 44 |
| 1 |
| 44 |
| EG001 | Ranitidine | Ranitidine 150 mg BID oral route was added to clopidogrel. | 0 | 48 | 0 | 48 |
|
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| D001161 |
| Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D011725 |
| Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D005663 | Furans |
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D058919 | Purinergic P2 Receptor Antagonists |
| D058914 | Purinergic Antagonists |
| D058905 | Purinergic Agents |
| D018377 | Neurotransmitter Agents |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D045505 | Physiological Effects of Drugs |