Abstract
Background: Dexketoprofen trometamol (DKP.TRIS) is the tromethamine salt of dexketoprofen, the S-enantiomer responsible for the pharmacological activity of ketoprofen. DKP.TRIS has rapid absorption and onset of action in pain relief.
Objective: To compare the efficacy and tolerability of DKP.TRIS and diclofenac, a nonsteroidal anti-inflammatory drug widely accepted as reference therapy for symptomatic treatment of osteoarthritis, in patients with chronic pain due to knee osteoarthritis.
Design: This was a multicentre, randomised, comparative, double-blind study.
Methods: Radiological evidence of osteoarthritis, shown by the presence of Kellgren grade 2 to 4 changes, was required. Patients were evaluated before and after a washout period of 7 to 14 days and after 1 and 2 weeks of treatment with DKP.TRIS 25mg three times daily orally or diclofenac 50mg three times daily orally. Primary end-points were reduction of pain measured on a visual analogue scale (VAS, 0 to 100mm) and disability measured by the Lequesne index of severity for knee osteoarthritis (ISK). Tolerability was evaluated by laboratory parameters and frequency and nature of adverse events.
Results: Of 117 patients recruited to the study, 115 were treated (61 with DKP.TRIS, 54 with diclofenac) and 99 (54/45) completed the 2-week treatment period. Patient characteristics were homogenous between groups. Pain measured on the VAS decreased by 43% from 61.7 ± 18.5mm (mean ± SD) at baseline to 34.7 ± 22.3mm at the end of treatment with DKP.TRIS compared with a 29% decrease from 62.1 ± 22.7mm to 40.6 ± 22.2mm for diclofenac [p = 0.027; 95% confidence interval (CI) for the difference between treatments: 1.7, 27.9]. Median ISK scores improved from 11 (range 9 to 12) to 8 (6 to 10) in the DKP.TRIS group versus 10.75 (9 to 12.5) to 8.5 (6 to 10.5) in the diclofenac group. There were no group differences for secondary end-points. Adverse events were comparable overall between groups.
Conclusion: Oral DKP.TRIS 25mg three times daily is at least as effective as diclofenac 50mg three times daily for the short term treatment of pain in patients with osteoarthritis of the knee.
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References
Swedberg JA. Osteoarthritis. Am Fam Physician 1992; 45: 557–68
Al Arfag A, Davis P. Osteoarthritis: current drug treatment regimens. Drugs 1991; 41(2): 193–201
Mauleön D, Artigas R, Garcia ML, et al. Preclinical and clinical development of dexketoprofen. Drugs 1996; 52Suppl. 5: 24–46
Beltrán J, Martín Mola E, Figueroa M, et al. Comparison of dexketoprofen trometamol and ketoprofen in the treatment of osteoarthritis of the knee. J Clin Pharmacol 1998; 38Suppl. 18: 74–80
Ezcurdia M, Cartejoso FJ, Lanzön R, et al. Comparison of the efficacy and tolerability of dexketoprofen and ketoprofen in the treatment of primary dysmenorrhea. J Clin Pharmacol 1998; 38Suppl. 18: 65–73
Gay C, Planas E, Donado M, et al. Analgesic effect of low doses of dexketoprofen in the dental pain model: a randomised, double-blind, placebo-controlled study. Clin Drug Invest 1996; 11:320–30
McGurk M, Robinson P, Rajayogeswaran V, et al. Clinical comparison of dexketoprofen trometamol, ketoprofen, and placebo in postoperative dental pain. J Clin Pharmacol 1998; 38Suppl. 18: 46–54
Bagán JV, López Arranz JS, Valencia E, et al. Clinical comparison of dexketoprofen trometamol and dipyrone in postoperative dental pain. J Clin Pharmacol 1998; 38Suppl. 18: 55–64
Veys EM. 20 years’ experience with ketoprofen. Scand J RheumatolSuppl. 1991; 90Suppl. 1: 1–44
Food and Drug Administration, US Department of Health and Human Services. Guidelines for the clinical evaluation of analgesic drugs. Bathesda (MD): Food and Drug Administration, 1992
British Medical Association and the Royal Pharmaceutical Association of Great Britain. Drugs used in the treatment of musculoskeletal and joint diseases. British National Formulary (London) 1996; 31: 403–25
European League Against Rheumatism. Guidelines for the clinical investigation of drugs used in rheumatic diseases. WHO Regional Office for Europe, Copenhagen, Denmark, March 1985
Food and Drug Administration, US Department of Health and Human Services. Guidelines for the clinical evaluation of anti-inflammatory and antirheumatic drugs (adults and children). Bethesda (MD):Food and Drug Administration, 1988
Lequesne MG, Mery C, Samson M, et al. Indexes of severity for osteoarthritis of the hip and knee. Validation — value in comparison with other assessment tests. Scand J Rheumatol Suppl. 1987; 65: 85–9
Kellgren JH, Lawrence JS. Radiological assessment of osteoarthritis. Am J Rheum Dis 1957; 16: 494–501
Bellamy N, Carette S, Ford PM. Osteoarthritis antirheumatic drug trials. I. Effects of standardization procedures on observer-dependent outcome measures. J Rheumatol 1992; 19: 436–43
Bellamy N, Carette S, Ford PM. Osteoarthritis antirheumatic drug trials. II. Tables for calculating sample size for clinical trials. J Rheumatol 1992; 19: 444–50
Bellamy N, Carette S, Ford PM. Osteoarthritis antirheumatic drug trials. III. Setting the delta for clinical trials. J Rheumatol 1992; 19:451–7
Dupont WD. Power and sample size calculations: a review and computer program. Control Clin Trials 1990; 11: 116–28
Carné X, Moreno V, Porta Serra M, et al. Epidemiología para clínicos: El cálculo del núméro de pacientes necessarios en la planificación de un estudio clínico. Med Clin (Barc) 1989; 92: 72–7
Kantor TG, Furst DE. Osteoarthritis. In: Max MB, Portenoy RK, Laska EM, editors. Advances in pain research and therapy. New York: Raven Press, 1991: 305–15
Caldwell J, Hutt AJ, Fournel-Gigleux S. The metabolic chiral inversion and dispositional enantioselectivity of the 2-aryl-propionic acids and their biological consequences. Biochem Pharmacol 1988; 37: 105–14
Cooper SA. Ketoprofen in oral surgery pain: a review. J Clin Pharmacol 1988; 28 (12 Suppl.): 40–6
Hayball P, Nation RL, Bochner F. Enantioselective pharmacodynamics of the nonsteroidal antiinflammatory drug ketoprofen: in vitro inhibition of human platelet cyclo-oxygenase activity. Chirality 1992; 4: 484–7
Suesa N, Fernández MF, Gutiérrez M, et al. Stereoselective cyclooxygenase inhibition in cellular models by the en-antiomers of ketoprofen. Chirality 1993; 5: 589–95
McCormack K, Urquhart E. Correlation between nonsteroidal anti-inflammatory drug efficacy in a clinical pain model and the dissociation of their anti-inflammatory and analgesic properties in animal models. Clin Drug Invest 1995; 9: 88–97
Barbanoj MJ, Gich I, Artigas R, et al. Pharmacokinetics of dexketoprofen trometamol in healthy volunteers after single and repeated doses. J Clin Pharmacol 1998; 38Suppl. 18: 73–80
McEwen J, De Luca M, Casini A, et al. The effect of food and an antacid on the bioavailability of dexketoprofen trometamol.J Clin Pharmacol 1998; 38Suppl. 18: 41–5
Fosslien E. Adverse effects of nonsteroidal anti-inflammatory drugs on the gastrointestinal system. Ann Clin Lab Sci 1998; 28: 67–81
Singh G, Ramey DR. NSAID induced gastrointestinal complications: the ARAMIS perspective — 1997. J Rheumatol 1998; 25Suppl. 51:8–16
Scheiman JM. NSAIDS and GI injury. Pt I. Epidemiology and pathogenesis. Drugs Today 1997; 33: 499–508
Insel PA. Analgesic-antipyretics and antiinflammatory agents; drugs employed in the treatment of rheumatoid arthritis and gout. In: Goodman S, Gilman A, Rall T, Nies AS, et al., editors. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. New York: Pergamon Press, 1990: 638–81
Hawkey C, Kahan A, Steinbrück K, et al., International Melissa Study Group. Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. Br J Rheumatol 1998; 37: 937–45
Porto A, Reis C, Perdigoto B, et al. Gastroduodenal tolerability of nimesulide and diclofenac in patients with osteoarthritis. Curr Ther Res 1998; 59: 654–65
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This study was supported by Laboratorios Menarini SA, Barcelona, Spain.
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Marenco, J.L., Pérez, M., Navarro, F.J. et al. A Multicentre, Randomised, Double-Blind Study to Compare the Efficacy and Tolerability of Dexketoprofen Trometamol versus Diclofenac in the Symptomatic Treatment of Knee Osteoarthritis. Clin. Drug Investig. 19, 247–256 (2000). https://doi.org/10.2165/00044011-200019040-00002
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DOI: https://doi.org/10.2165/00044011-200019040-00002