title: [Treating pain after dental surgery: a randomised, controlled, double-blind trial to assess a new formulation of paracetamol, opium powder and caffeine versus tramadol or placebo].
abstract: BACKGROUND
  The aim of this study was to evaluate the analgesic efficacy and the safety of the association, paracetamol, opium prepared and caffeine, in two different dosages as compared to the conventional analgesic tramadol hydrochloride, on acute postoperative dental pain.
  
  
  METHODS
  We conducted a randomised, double-blind, multicentre, parallel-group clinical trial to test the efficacy and safety of single doses of two associations; paracetamol 500 mg, caffeine 50mg, opium prepared 25, and paracetamol 500 mg, caffeine 50mg, opium prepared 50mg, as compared to tramadol hydrochloride 100mg (called hereafter tramadol 100), and placebo, in the control of postoperative pain following the removal of 2 ipsilateral impacted third molars. The primary efficacy criterion was the sum of pain intensity differences as assessed every 30 minutes within 3 hours after the baseline assessment and administration of study treatment (SPID(0-3h)).
  
  
  RESULTS
  Of the 232 randomised patients, 228 (98%) completed the study. Analysis of the primary efficacy criterion (SPID(0-3h)) established: (i) the superiority of the 3 active study treatments vs. placebo (p<0.005); (ii) non-inferiority of paracetamol, caffeine, and opium 25mg, and paracetamol, caffeine, and opium 50mg vs. tramadol. Besides, both formulations of paracetamol, caffeine, and opium showed: (i) a faster onset of analgesic effect as compared to tramadol 100; (ii) a significantly stronger analgesic efficacy than tramadol 100, as measured 1 hour after the treatment intake; this superiority lasted all over the study duration for paracetamol, caffeine, and opium 50mg but not for paracetamol, caffeine, and opium 25mg. No unexpected safety concerns occurred, the two formulations of paracetamol, caffeine, and opium showed a good safety profile especially with paracetamol, caffeine, and opium 25mg as compared to tramadol.
  
  
  CONCLUSIONS
  This study evidenced the non-inferiority of the paracetamol, caffeine, and opium 25mg or 50mg vs. tramadol 100, and even though the strengths of the tested formulations were higher than that of the 2009, commercialised formulation of paracetamol, caffeine, and opium, efficacy was not offset by an alteration of the well recognised safety profile of the less strengthened formulation of the product being in use for decades.
authors.affiliation: CHU de Clermont-Ferrand, 63000 Clermont-Ferrand, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Borel
authors.forename: Christophe
authors.initials: C
authors.lastname: Deschaumes
authors.forename: Laurent
authors.initials: L
authors.lastname: Devoize
authors.forename: Cédric
authors.initials: C
authors.lastname: Huard
authors.forename: Thierry
authors.initials: T
authors.lastname: Orliaguet
authors.forename: Claude
authors.initials: C
authors.lastname: Dubray
authors.forename: Martine
authors.initials: M
authors.lastname: Baudet-Pommel
authors.forename: Radhouane
authors.initials: R
authors.lastname: Dallel
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000627:therapeutic use*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000627:therapeutic use*; D002110:Caffeine / Q000008:administration & dosage / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000627:therapeutic use*; D002626:Chemistry, Pharmaceutical; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008964:Molar, Third / Q000601:surgery; D009892:Opium / Q000008:administration & dosage / Q000627:therapeutic use*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D010919:Placebos; D012449:Safety; D014081:Tooth Extraction; D014095:Tooth, Impacted / Q000601:surgery; D014147:Tramadol / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000697:Central Nervous System Stimulants; D004338:Drug Combinations; D010919:Placebos; D000082:Acetaminophen; D014147:Tramadol; D002110:Caffeine; D009892:Opium