title: Randomized clinical trial of dexketoprofen/tramadol 25 mg/75 mg in moderate-to-severe pain after total hip arthroplasty.
abstract: BACKGROUND
  The aim was to evaluate the analgesic efficacy and safety of the dexketoprofen/tramadol 25 mg/75 mg fixed-dose combination vs dexketoprofen (25 mg) and tramadol (100 mg) in moderate-to-severe acute pain after total hip arthroplasty.
  
  
  METHODS
  This was a randomized, double-blind, parallel-group study in patients experiencing pain of at least moderate intensity on the day after surgery, compared with placebo at first administration to validate the pain model. The study drug was administered orally every 8 h throughout a 5 day period. Rescue medication, metamizole 500 mg, was available during the treatment period. The evaluation of efficacy was based on patient assessments of pain intensity and pain relief. The primary end point was the mean sum of the pain intensity difference values throughout the first 8 h (SPID8).
  
  
  RESULTS
  Overall, 641 patients, mean age 62 (range 29-80) yr, were analysed; mean (sd) values of SPID8 were 247 (157) for dexketoprofen/tramadol, 209 (155) for dexketoprofen, 205 (146) for tramadol, and 151 (159) for placebo. The primary analysis confirmed the superiority of the combination over dexketoprofen 25 mg (P=0.019; 95% confidence interval 6.4-73) and tramadol 100 mg (P=0.012; 95% confidence interval 9.5-76). The single components were superior to placebo (P<0.05), confirming model sensitivity. Most secondary analyses supported the superiority of the combination. The incidence of adverse drug reactions was low and similar among active treatment groups.
  
  
  CONCLUSIONS
  The efficacy results confirmed the superiority of dexketoprofen/tramadol over its single components, even at higher doses (tramadol), with a safety profile fully in line with that previously known for these agents in monotherapy.
  
  
  BACKGROUND
  EudraCT 2012-004548-31 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-004548-31);ClinicalTrials.gov NCT01902134 (https://www.clinicaltrials.gov/ct2/show/NCT01902134?term=NCT01902134&rank=1).
authors.affiliation: Balliol College, University of Oxford, Oxford, UK henrymcquay@gmail.com.
authors.forename: H J
authors.initials: HJ
authors.lastname: McQuay
authors.affiliation: Pain Research & Nuffield Division of Anaesthetics, University of Oxford, The Churchill, Oxford OX1 3BJ, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Moore
authors.affiliation: Department of Orthopaedics, Uzsoki Hospital, Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Berta
authors.affiliation: Department of Joint Surgery, Hospital of Traumatology and Orthopaedics, Riga, Latvia.
authors.forename: O
authors.initials: O
authors.lastname: Gainutdinovs
authors.affiliation: Department of Anesthesiology and Intensive Care, University of Debrecen, Debrecen, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Fülesdi
authors.affiliation: Department of Traumatology and Orthopaedics, Republican Vilnius University Hospital, Vilnius, Lithuania.
authors.forename: N
authors.initials: N
authors.lastname: Porvaneckas
authors.affiliation: Department of Traumatology and Orthopaedics, Riga's 2nd Hospital, Riga, Latvia.
authors.forename: S
authors.initials: S
authors.lastname: Petronis
authors.affiliation: Clinic for Orthopaedics and Traumatology, Clinical Center Nis, University of Nis, Nis, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Mitkovic
authors.affiliation: Department of Orthopaedics, St George University Teaching Hospital, Szekesfehervar, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Bucsi
authors.affiliation: Department of Orthopaedics, MÁV Hospital, Szolnok, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Samson
authors.affiliation: Department of Traumatology, Klaipeda University Hospital, Klaipeda, Lithuania.
authors.forename: V
authors.initials: V
authors.lastname: Zegunis
authors.affiliation: Orthopedic & Trauma Center, Kiev Regional Clinical Hospital, Kiev, Ukraine.
authors.forename: M L
authors.initials: ML
authors.lastname: Ankin
authors.affiliation: Clinical Research, Menarini Ricerche S.p.A. - Menarini Group, Florence, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bertolotti
authors.affiliation: Clinical Research, Laboratorios Menarini S.A. - Menarini Group, Badalona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Pizà-Vallespir
authors.affiliation: Clinical Research, Laboratorios Menarini S.A. - Menarini Group, Badalona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Cuadripani
authors.affiliation: Clinical Research, Menarini Ricerche S.p.A. - Menarini Group, Florence, Italy.
authors.forename: M P
authors.initials: MP
authors.lastname: Contini
authors.affiliation: Clinical Research, Menarini Ricerche S.p.A. - Menarini Group, Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Nizzardo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007660:Ketoprofen / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D012720:Severity of Illness Index; D014147:Tramadol / Q000627:therapeutic use*; D016896:Treatment Outcome; D014325:Tromethamine / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014325:Tromethamine; D014147:Tramadol; D007660:Ketoprofen; C118296:dexketoprofen trometamol
keywords: analgesics; arthroplasty, replacement, hip; dexketoprofen trometamol; pain, postoperative; tramadol