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Meloxicam is a new nonsterial anti-inflammatory drugs(NSAIDs), of the enolic acid class. The structure of meloxicam is similar to piroxicam and tenoxicam. It inhibited prostaglandin production, like other NSAIDs. Meloxicam has been approved in Europe, in 1995, for treatment of rheumatic arthritis(RA) and osteoarthritis(OA). More than 20,000 patients completed clinical trial, but in Taiwan we have no more information about its safety profile. So with thistrial, wewant to known the safety profile of meloxicam in OA patients ofTaiwan.We designed a prospective, double-blind, double-dummy, randomized, parallel- group clinical trial, in ten medical centers in Taiwan. The subjects must be the outpatients of hip or knee OA, over 18 years old and pain on active movement exceeding 35mm by Visual Analogue Scale(VAS). The patients with active peptic ulcer, impairment of hepatic and renal function, or hyper- sensitivity to the trial drugs or other NSAIDs must be excluded. Following awash-out period for the previously taken NSAIDs of at least three days,patients were administered either meloxicam 7.5mg with one diclofenac-placebo once daily or diclofenac slow- releases 100mg with meloxicam-placebo once dailyaccording to the randomization scheme for 28 days. Final gloabl assessment of efficacy, pain on active movement, pain at rest, chang of arthritis condition,withdrawal due to inadequate efficacy and improvement of the Western Onterioand McMaster Universities Osteoarthritis Index were the main efficacy endpoints.Adverse events in terms of incidence, intensity, causal relationship to the trial drugs, withdrawals due to adverse events and change in laboratory valuesand tolerability were the main safety endpoints. In the inten-to-treat analysis, the frequencies of AEs in the two treatment groups were compared by calculat-ing odds rations; GI adverse events were compared by Fisher''s exact test. Differences of efficacy endpoints on the VAS were analyzed by two-side t-test.This trial was carried out in accordance with the Declaration of Helsinki, in accordance with Good Clinical Practice(GCP) and local laws. This protocol wassubmitted to the Joint Institution Review oard of Taiwan(JIRB) for ethicalreview, and reviewed by the Institution Review Board(IRB) of the hospital.October 1997 throug may 1998, overall of 343 patients were evaluated for studyeligibility, of which 282 patients received trial medication (meloxicam140;diclofenac 142). A total of 236 patients completed the trial (meloxicam 124;diclofenac 112). There was no difference between the two treatment groups withrespect to the efficacy variables. Withdrawals due to lack of efficacy occurredrarely in the both group, 1.43% in meloxicam group, and 3.5% in diclofenacgroup. The number of premature discontinuations due to AEs was significantlylower in the meloxicam group (3.57%) than in the diclofenac group (11.97%)(p=0.009; odds ratio 0.272). Significantly fewer gastrointestinal adverse eventswere reported in the meloxicam group (40.0%) compared with the diclofenac (54.23%)(p=0.017; odds ratio 0.563). The overall clinical laboratory findingsof meloxicam were comparable to those of diclofenac. SAEs were reported in zeropatient receiving meloxicam and one patient receiving diclofenac. AEs of the PUB category (perforation, ulceration, bleeding) were reported in three patients (all ulcer) treated with diclofenac and in no patient treated withmeloxicam. In conclusion, meloxicam 7.5mg once daily was as effective as diclofenac 100mg s.r. once daily in Taiwan patients with acute symptomtic osteoarthritis. Meloxicam demonstrated a more favourable gastrointestinal tolerability compared with diclofenac s.r.
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