Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain

The Journal of Headache and Pain

Research Article

S. Milleri¹  C. Guerrero-Bayón²  B. Pizà-Vallespir²  S. Cuadripani²  C. A. Maggi³  M. Bertolotti³  S. Scartoni³  M. P. Contini³  A. Capriati³  A. Nizzardo³  M. Peñarrocha-Diago⁴  A. García-García⁵  A. Wojtowicz⁶  D. Matenko⁶  C. Gay-Escoda⁷  R. Figueiredo⁷  Z. Tóth-Bagi⁸  D. Torres-Lagares⁹  R. Andrew Moore^1,10  P. Coulthard^1,11  T. Dietrich^1,12  C. M. Hill^1,13 

[1] Centro Ricerche Cliniche, Ospedale Policlinico G.B.Rossi, Verona, Italy;Clinical Research, Laboratorios Menarini S.A. – Menarini Group, Badalona, Spain;Clinical Research, Menarini Ricerche S.p.A – Menarini Group, Florence, Italy;Departament d’Estomatologia, Clínica Odontológica, Universidad de Valencia, Valencia, Spain;Department of Maxillofacial Surgery, Hospital Médico Quirúrgico de Conxo, Santiago de Compostela, Spain;Department of Oral Surgery, Warsaw Medical Univeristy, Warsaw, Poland;Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Barcelona, Bellvitge Institute for Biomedical Research (IDIBELL), Barcelona, Spain;Dr. Tóth Bagi Zoltán Fogászati Rendeloje, Budapest, Hungary;Hospital Universitario Virgen del Rocío, Departamento de Estomatología, Facultad de Odontología, Universidad de Sevilla, Sevilla, Spain;Pain Research and Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurology, University of Oxford, The Churchill, OX3 7LE, Oxford, UK;School of Dentistry, University of Manchester, Manchester, UK;The School of Dentistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK;University Dental Hospital, Cardiff, UK;

关键词: Dexketoprofen;    Tramadol;    Combination analgesics;    Postoperative pain;    Third molar;    Randomised controlled trial;    Dose range;   

DOI  :  10.1186/s10194-015-0541-5

 received in 2015-04-29, accepted in 2015-06-12,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundCombination analgesics are effective in acute pain, and a theoretical framework predicts efficacy for combinations. The combination of dexketoprofen and tramadol is untested, but predicted to be highly effective.MethodsThis was a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, single-dose trial in patients with moderate or severe pain following third molar extraction. There were ten treatment arms, including dexketoprofen trometamol (12.5 mg and 25 mg) and tramadol hydrochloride (37.5 mg and 75 mg), given as four different fixed combinations and single components, with ibuprofen 400 mg as active control as well as a placebo control. The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo. The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours.Results606 patients were randomised and provided at least one post-dose assessment. All combinations were significantly better than placebo. The highest percentage of responders (72 %) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group (NNT 1.6, 95 % confidence interval 1.3 to 2.1). Addition of tramadol to dexketoprofen resulted in greater peak pain relief and greater pain relief over the longer term, particularly at times longer than six hours (median duration of 8.1 h). Adverse events were unremarkable.ConclusionsDexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain. The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae.Trial registrationEudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).

【 授权许可】

CC BY   
© Moore et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.