Prospective Randomized Evaluation Of Celecoxib Integrated Safety Vs Ibuprofen Or Naproxen

Study Overview
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Brief Summary
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To answer the question of overall benefit: risk of celecoxib when compared to two most commonly prescribe traditional (non-selective) nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of arthritis pain. For this purpose, patients with osteoarthritis or rheumatoid arthritis with or at risk of developing cardiovascular disease will be recruited. The cardiovascular, gastrointestinal and renal safety and symptomatic benefit in each treatment group will be assessed accordingly.

Official Title
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A Randomized, Double Blind, Parallel-group Study Of Cardiovascular Safety In Osteoarthritis Or Rheumatoid Arthritis Patients With Or At High Risk For Cardiovascular Disease Comparing Celecoxib With Naproxen And Ibuprofen

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: celecoxib
* Drug: Ibuprofen
* Drug: Naproxen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with osteoarthritis or rheumatoid Arthritis with or at risk of developing cardiovascular disease and who require and eligible for chronic, daily therapy with an NSAID to control arthritis sign and symptoms. Exclusion Criteria: Subjects have had a recent cardiovascular event, unstable cardiovascular conditions, or any major surgery (cardiac or non-cardiac) within 3 months prior to randomization; Subjects with medical or laboratory abnormality that would make the subject inappropriate for entry into this trial Subjects require treatment with aspirin > 325 mg /day Subjects with known hypersensitivity to celecoxib, ibuprofen, naproxen, aspirin or esomeprazole, etc.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: celecoxib<br>subject receives celecoxib and dummy (placebo) ibuprofen and naproxen | Drug: celecoxib<br>* 100 to 200 mg twice daily, taken by mouth<br>|
| Active Comparator: ibuprofen<br>subject receives ibuprofen and dummy (placebo) celecoxib and naproxen | Drug: Ibuprofen<br>* ibuprofen 600 mg to 800 mg three times daily, taken by mouth<br>|
| Active Comparator: naproxen<br>subject receives naproxen and dummy (placebo) celecoxib and ibuprofen | Drug: Naproxen<br>* naproxen 375mg to 500 mg twice daily, taken by mouth<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The First Occurrence of Antiplatelet Trialists Collaboration (APTC) Composite Endpoint, Confirmed by the Clinical Events Committee (CEC). | APTC events are defined as a composite of any of the following events: Death due to CV causes (including cardiac, cerebrovascular, venous thromboembolic, haemorrhagic, other vascular, or unknown cause); Non-fatal MI; Non-fatal stroke (including intracranial hemorrhages, stroke of ischemic or unknown etiology). | Intent to Treat (ITT) Population - 30 months; Modified ITT (MITT) Population - 42 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The First Occurrence of a Major Adverse Cardiovascular Events (MACE) | MACE defined as the composite of CV death (including hemorrhagic death), non-fatal MI, non-fatal stroke, hospitalization for UA, revascularization or hospitalization for TIA | ITT Population - 30 months; MITT Population - 42 months | 
| The First Occurrence of Clinically Significant Gastrointestinal Events (CSGIE) | CSGIE include: Gastroduodenal (GD) hemorrhage, Gastric outlet obstruction, Gastroduodenal, small bowel or large bowel perforation, Large bowel hemorrhage, Small bowel hemorrhage, Acute GI hemorrhage of unknown origin, including presumed small bowel hemorrhage, Symptomatic gastric or duodenal ulcer | ITT Population - 30 months; MITT Population - 42 months | 
| Change From Baseline in Patient's Assessment of Arthritis Pain (VAS) | VAS question How much pain do you have was graded on a scale from 0 to 100 with 0 indicating No pain and 100 indicating Worst possible pain. | ITT and MITT Population - Baseline to 42 months |