Significance & Background Information: Celecoxib (SC-58635) is the first specific inhibitor of the enzyme cyclooxygenase-2, which is responsible for much of the inflammation in osteoarthritis (OA) and rheumatoid arthritis (RA). Older non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, also inhibit this enzyme, but in addition, they inhibit cyclooxygenase-1, which leads to the side effects (gastritis, ulcers, blood """"""""""""""""thinning"""""""""""""""") seen with NSAID use. Clinical trials of Celebrex for patients with OA and RA showed excellent relief of joint pain, stiffness and swelling (equal to naproxen, ibuprofen or diclofenac), and a much lower incidence of stomach irritation (determined by endoscopy--looking into the stomach with a lighted tube) than the older NSAIDs. Most of the irritation seen with an endoscope never causes the patient to have any symptoms. It is therefore more relevant to find out if Celebrex causes less """"""""""""""""clinically significant upper gastrointestinal adverse events"""""""""""""""" than the older NSAIDs (meaning the type of problems that would bring a patient to a physician). Hypothesis: Administration of Celebrex 400mg twice daily will result in less clinically significant upper gastrointestinal (UGI) adverse events than administration of diclofenac (brand name: Voltaren) 75mg twice daily or naproxen 500mg twice daily. Specifically, the incidence of bleeding, perforation or gastric outlet obstruction will be assessed. This dose of Celebrex was chosen because it is actually twice the usual dosage for the treatment of arthritis, and this represents a true test of the potential of the drug to cause clinically significant UGI adverse events. This dosage has been used in earlier clinical trials, and was not associated with more adverse events than the lower dosages. Here at UT-Houston, we will be comparing Celebrex with diclofenac (number one selling NSAID in Europe) whereas other sites will compare with naproxen (number one selling NSAID in US). Primary Objective: Compare the incidence of perforation, bleeding or gastric outlet obstruction associated with chronic administration of Celebrex 400mg twice daily with that associated with chronic administration of diclofenac 75mg twice daily or naproxen 500mg twice daily in patients with OA or RA. The primary analyses of this study will consist of a survival analysis of the UGI adverse events in this study pooled with those in a companion study (N49-98-02-035). Secondary Objectives: 1. Compare the chronic overall safety and tolerability of Celebrex versus diclofenac and naproxen. 2. Compare the effect of Celebrex versus diclofenac and naproxen on quality of life and patient satisfaction. 3. Compare the effect of Celebrex versus diclofenac and naproxen on indirect costs. 4. Compare the long-term efficacy of Celebrex versus diclofenac and naproxen for the treatment of OA and RA.
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