Celecoxib Versus Naproxen for Prevention of Recurrent Ulcer Bleeding in Arthritis Patients

Study Overview
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Brief Summary
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The aim of this study is to compare celecoxib plus a PPI (esomeprazole) versus naproxen plus a PPI (esomeprazole) in preventing recurrent ulcer bleeding in arthritis patients with a history of ulcer bleeding who require concomitant ASA. We hypothesized that among patients with a history of ulcer bleeding who require concomitant ASA, celecoxib plus esomprazole would be superior to naproxen plus esomeprazole for the prevention of recurrent ulcer bleeding.

Detailed Description
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Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly consumed drugs worldwide for the relief of pain and arthritis. However, the use of NSAIDs increases the risk of ulcer bleeding by 4-fold. Current evidence indicates that combination of conventional NSAIDs and a proton pump inhibitor (PPI) reduces the risk of ulcer complications. The alternative strategy is to replace conventional, non-selective NSAIDs with NSAIDs selective for cyclooxygenase-2 (COX-2 inhibitors). Recently, there are concerns about the cardiovascular safety of COX-2 inhibitors and conventional NSAIDs. Because of such concern, patients requiring anti-inflammatory analgesics who have cardiovascular risk factors (e.g. smoking, hypertension, hyperlipidemia, diabetes) should receive prophylactic low-dose aspirin. However, concomitant low-dose aspirin negates the gastric sparing effect of COX-2 inhibitors and augments the gastric toxicity of nonselective NSAIDs. Thus, gastroprotective agents such as PPIs should be co-prescribed to patients with high ulcer risk who are taking aspirin plus a COX-2 inhibitor or a nonselective NSAID.

Official Title
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A Double-blind Randomized Comparison of Celecoxib Plus Esomeprazole Versus Naproxen Plus Esomeprazole for Prevention of Recurrent Ulcer Bleeding in Patients With Arthritis and Cardiothrombotic Diseases (NSAID#8 Study)

Conditions
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Arthritis, Cardiovascular Diseases, Cerebrovascular Disorders

Intervention / Treatment
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* Drug: Celecoxib(drug)
* Drug: Naproxen(drug)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age >18, a history of endoscopically proven gastroduodenal ulcer bleeding, H. pylori negative a history of cardiothrombotic disease requiring ASA, and anticipated regular use of NSAIDs for the duration of trial Exclusion Criteria: concomitant use of anticoagulants; a history of gastric or duodenal surgery other than a patch repair; the presence of erosive esophagitis, gastric outlet obstruction, renal failure (defined by a serum creatinine level of more than 200 umol/L), pregnancy, terminal illness, or cancer

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NSAID #1<br>Celecoxib and Naproxen Placebo | Drug: Celecoxib(drug)<br>* Celecoxib 100 mg bd<br>* Other names: Celebrex;|
| Active Comparator: NSAID #2<br>Naproxen and Celecoxib Placebo | Drug: Naproxen(drug)<br>* Naproxen 500 mg bd<br>* Other names: Naprosyn;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent ulcer bleeding within 18 months according to pre-specified criteria |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patients' global assessment of arthritis |  | 18 months | 
| major CV events according to the Antithrombotic Trialists' criteria |  | 18 months | 
| non-fatal myocardial infarction |  | 18 months | 
| non-fatal stroke |  | 18 months | 
| death from a vascular cause |  | 18 months |