title: Dexketoprofen/tramadol: randomised double-blind trial and confirmation of empirical theory of combination analgesics in acute pain.
abstract: BACKGROUND
  Combination 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.
  
  
  METHODS
  This 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.
  
  
  RESULTS
  606 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.
  
  
  CONCLUSIONS
  Dexketoprofen 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.
  
  
  BACKGROUND
  EudraCT (2010-022798-32); Clinicaltrials.gov (NCT01307020).
authors.affiliation: Pain Research and Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurology, University of Oxford, The Churchill, Oxford, OX3 7LE, UK, andrew.moore@ndcn.ox.ac.uk.
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Moore
authors.forename: C
authors.initials: C
authors.lastname: Gay-Escoda
authors.forename: R
authors.initials: R
authors.lastname: Figueiredo
authors.forename: Z
authors.initials: Z
authors.lastname: Tóth-Bagi
authors.forename: T
authors.initials: T
authors.lastname: Dietrich
authors.forename: S
authors.initials: S
authors.lastname: Milleri
authors.forename: D
authors.initials: D
authors.lastname: Torres-Lagares
authors.forename: C M
authors.initials: CM
authors.lastname: Hill
authors.forename: A
authors.initials: A
authors.lastname: García-García
authors.forename: P
authors.initials: P
authors.lastname: Coulthard
authors.forename: A
authors.initials: A
authors.lastname: Wojtowicz
authors.forename: D
authors.initials: D
authors.lastname: Matenko
authors.forename: M
authors.initials: M
authors.lastname: Peñarrocha-Diago
authors.forename: S
authors.initials: S
authors.lastname: Cuadripani
authors.forename: B
authors.initials: B
authors.lastname: Pizà-Vallespir
authors.forename: C
authors.initials: C
authors.lastname: Guerrero-Bayón
authors.forename: M
authors.initials: M
authors.lastname: Bertolotti
authors.forename: M P
authors.initials: MP
authors.lastname: Contini
authors.forename: S
authors.initials: S
authors.lastname: Scartoni
authors.forename: A
authors.initials: A
authors.lastname: Nizzardo
authors.forename: A
authors.initials: A
authors.lastname: Capriati
authors.forename: C A
authors.initials: CA
authors.lastname: Maggi
mesh_terms: D059787:Acute Pain / Q000175:diagnosis / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000698:Analgesia / Q000379:methods; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D036262:Empirical Research; D005260:Female; D006801:Humans; D007660:Ketoprofen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D059408:Pain Management / Q000379:methods; D014147:Tramadol / Q000008:administration & dosage*; D014325:Tromethamine / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014325:Tromethamine; D014147:Tramadol; D007660:Ketoprofen; C118296:dexketoprofen trometamol