title: Dexketoprofen/tramadol 25 mg/75 mg: randomised double-blind trial in moderate-to-severe acute pain after abdominal hysterectomy.
abstract: BACKGROUND
  Dexketoprofen trometamol plus tramadol hydrochloride is a new oral combination of two analgesics, which have different mechanisms of action for the treatment of moderate to severe acute pain.
  
  
  METHODS
  Randomised, double-blind, parallel, placebo and active-controlled, single and multiple-dose study to evaluate the analgesic efficacy and safety of dexketoprofen/tramadol 25 mg/75 mg in comparison with the single agents (dexketoprofen 25 mg and tramadol 100 mg) in moderate to severe acute pain after abdominal hysterectomy. Patients received seven consecutive doses of study drug within a 3-day period, each dose separated by an 8-hour interval. A placebo arm was included during the single-dose phase to validate the pain model. Efficacy assessments included pain intensity, pain relief, patient global evaluation and use of rescue medication. The primary endpoint was the mean sum of pain intensity differences over the first 8 h (SPID8).
  
  
  RESULTS
  The efficacy analysis included 606 patients, with a mean age of 48 years (range 25-73). The study results confirmed the superiority of the combination over the single agents in terms of the primary endpoint (p <0.001). Secondary endpoints were generally supportive of the superiority of the combination for both single and multiple doses. Most common adverse drug reactions (ADRs) were nausea (4.6%) and vomiting (2.3%). All other ADRs were experienced by less than 2% of patients.
  
  
  CONCLUSIONS
  The study results provided robust evidence of the superiority of dexketoprofen/tramadol 25 mg/75 mg over the single components in the management of moderate to severe acute pain, as confirmed by the single-dose efficacy, repeated-dose sustained effect and good safety profile observed.
  
  
  BACKGROUND
  EU Clinical Trials Register (EudraCT number 2012-004545-32, registered 04 October 2012); Clinicaltrials.gov ( NCT01904149, registered 17 July 2013).
authors.affiliation: Pain Research & Nuffield Division of Anaesthetics, University of Oxford, The Churchill, Oxford, UK. andrew.moore@ndcn.ox.ac.uk.
authors.forename: R A
authors.initials: RA
authors.lastname: Moore
authors.affiliation: Balliol College, University of Oxford, Oxford, UK.
authors.forename: H J
authors.initials: HJ
authors.lastname: McQuay
authors.affiliation: Obstetrics-Gynaecology Private Clinic, Bialystok, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Tomaszewski
authors.affiliation: Division of Gynaecology, Provincial Hospital in Przemysl, Przemysl, Poland.
authors.forename: G
authors.initials: G
authors.lastname: Raba
authors.affiliation: Genesys Fertility Center, Bucharest, Romania.
authors.forename: D
authors.initials: D
authors.lastname: Tutunaru
authors.affiliation: Gynaecology, Riga East University Hospital Gynaecology Clinic, Riga, Latvia.
authors.forename: N
authors.initials: N
authors.lastname: Lietuviete
authors.affiliation: GYNPOR, s.r.o., Sliac, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Galad
authors.affiliation: Gynaecological Department, St. George Fejer County Teaching Hospital, Szekesfehervar, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Hagymasy
authors.affiliation: Gynaecological Department, Latvian marine Medical Center, Riga, Latvia.
authors.forename: D
authors.initials: D
authors.lastname: Melka
authors.affiliation: I Department of Gynaecological Oncology and Gynaecology, Medical University Hospital No 1, Lublin, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Kotarski
authors.affiliation: II Department of Gynaecology, Medical University Hospital No 4, Lublin, Poland.
authors.forename: T
authors.initials: T
authors.lastname: Rechberger
authors.affiliation: Department of Anaesthesiology and Intensive Care, University of Debrecen, Debrecen, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Fülesdi
authors.affiliation: Clinical Research, Menarini Ricerche S.p.A - Menarini Group, Florence, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Nizzardo
authors.affiliation: Clinical Research, Laboratorios Menarini S.A. - Menarini Group, Badalona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Guerrero-Bayón
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, Laboratorios Menarini S.A. - Menarini Group, Badalona, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Pizà-Vallespir
authors.affiliation: Clinical Research, Menarini Ricerche S.p.A - Menarini Group, Florence, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Bertolotti
mesh_terms: D059787:Acute Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007044:Hysterectomy / Q000009:adverse effects*; D007660:Ketoprofen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008875:Middle Aged; D059408:Pain Management / Q000379:methods; D010149:Postoperative Pain / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D012720:Severity of Illness Index; D014147:Tramadol / Q000008:administration & dosage*; D014325:Tromethamine / Q000008:administration & dosage*
chemical_list: D000701:Analgesics, Opioid; D014325:Tromethamine; D014147:Tramadol; D007660:Ketoprofen; C118296:dexketoprofen trometamol