Celecoxib, Ibuprofen and the Antiplatelet Effect of Aspirin

Study Overview
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Brief Summary
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Study design: Single center, placebo-controlled, double blind, parallel groups. To evaluate the potential interaction between aspirin and ibuprofen or celecoxib in patients with osteoarthritis (OA) and documented stable ischemic heart disease, a total of 24 patients chronically treated with aspirin will be randomly assigned to one of the 3 treatment groups: 1) celecoxib 200 mg bid; 2) ibuprofen 600 mg tid; 3) placebo.

Detailed Description
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Patients with arthritis and vascular disease may receive both NSAIDs and lowdose aspirin for the secondary prevention of important vascular events. The use of COX-2 inhibitors may have the potential advantage vs. nonselective NSAIDs in reducing the probability of interfering with permanent inactivation of COX-1 platelet by low-dose aspirin, in this setting. In fact, recent studies suggest that the likelihood of COX-inhibitors to present this pharmacodynamic interaction is inversely related to their COX-2 selectivity. Thus, differently from the non-selective NSAID ibuprofen, prior administration of the selective COX-2 inhibitor rofecoxib, does not antagonize the irreversible inhibition induced by aspirin in healthy subjects. Aim of this study is to determine whether celecoxib given at therapeutic dose at steady state alters the antiplatelet activity of low-dose aspirin, in comparison with ibuprofen.

Official Title
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A Placebo-Controlled, Double-Blind, Randomized Study of the Potential Interaction Between Aspirin and Ibuprofen or Celecoxib.

Conditions
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Ischemic Heart Disease, Osteoarthritis

Intervention / Treatment
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* Drug: celecoxib
* Drug: ibuprofen
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female, age 18-75; subjects with osteoarthritis and documented stable ischemic heart disease; the patient is on long-term aspirin prophylaxis for the ischemic condition; the patient requires or is eligible for chronic treatment with an antiinflammatory and/or analgesic drugs given to control osteoarthritis symptoms; female subjects of childbearing potential must have a negative pregnancy test, use adequate contraception during the study and not be lactating; written informed consent before undergoing any study procedure. Exclusion Criteria: active gastrointestinal disease (e.g. Crohn's disease or ulcerative colitis) or any evidence of concomitant disease which may lead to early termination of the study; history of active peptic ulceration, gastrointestinal bleeding, esophageal, gastric or duodenal ulcer; known hypersensitivity to COX-2 inhibitors, analgesics, antipyretics, sulfonamides or NSAIDs; treatment with any investigational drug within the previous 30 days; previous participation in this study; evidence of neoplasm or any other severe disease of any organ, including any psychiatric illness; clinically relevant deviations from the normal range in laboratory tests; recent history or suspicion of alcohol abuse or drug addiction; subjects unlikely to be collaborative or to give reliable answers; pregnancy or lactation; female or childbearing potential without a clinical accepted contraceptive method; any severe pathology that can interfere with the treatment or the clinical or instrumental tests of the trial; intake of antiaggregant, anticoagulant, diuretic, beta-blocker, ACE- inhibitor, lithium, methotrexate, cimetidine, digoxin; contraindications to NSAIDs.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: celecoxib<br>* celecoxib capsules 200 mg bid for 1 week<br>|
| Experimental: 2<br> | Drug: ibuprofen<br>* ibuprofen tablets 600 mg tid for 1 week<br>|
| Placebo Comparator: 3<br> | Drug: placebo<br>* placebo capsules tid for 1 week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum thromboxane (TX)B2 |  | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| urinary 11-dehydro-thromboxane (TX)B2, arachidonic acid- and ADP-induced platelet aggregation by Born's aggregometer, whole-blood aggregation in the platelet function analyzer (PFA) system, LPS-stimulated prostaglandin(PG)E2 |  | 1 week |