title: Evaluation of etoricoxib in patients undergoing total knee replacement surgery in a double-blind, randomized controlled trial.
abstract: BACKGROUND
  Optimal postoperative pain management is important to ensure patient comfort and early mobilization.
  
  
  METHODS
  In this double-blind, placebo- and active-controlled, randomized clinical trial, we evaluated postoperative pain following knee replacement in patients receiving placebo, etoricoxib (90 or 120 mg), or ibuprofen 1800 mg daily for 7 days. Patients ≥18 years of age who had pain at rest ≥5 (0-10 Numerical Rating Scale [NRS]) after unilateral total knee replacement were randomly assigned to placebo (N = 98), etoricoxib 90 mg (N = 224), etoricoxib 120 mg (N = 230), or ibuprofen 1800 mg (N = 224) postoperatively. Co-primary endpoints included Average Pain Intensity Difference at Rest over Days 1-3 (0- to 10-point NRS) and Average Total Daily Dose of Morphine over Days 1-3. Pain upon movement was evaluated using Average Pain Intensity Difference upon Knee Flexion (0- to 10-point NRS). The primary objective was to demonstrate analgesic superiority for the etoricoxib doses vs. placebo; the secondary objective was to demonstrate that the analgesic effect of the etoricoxib doses was non-inferior to ibuprofen. Adverse experiences (AEs) including opioid-related AEs were evaluated.
  
  
  RESULTS
  The least squares (LS) mean (95% CI) differences from placebo for Pain Intensity Difference at Rest over Days 1-3 were -0.54 (-0.95, -0.14); -0.49 (-0.89, -0.08); and -0.45 (-0.85, -0.04) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.05 for etoricoxib vs. placebo). Differences in LS Geometric Mean Ratio morphine use over Days 1-3 from placebo were 0.66 (0.54, 0.82); 0.69 (0.56, 0.85); and 0.66 (0.53, 0.81) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.001 for etoricoxib vs. placebo). Differences in LS Mean Pain Intensity upon Knee Flexion were -0.37 (-0.85, 0.11); -0.46 (-0.94, 0.01); and -0.42 (-0.90, 0.06) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. Opioid-related AEs occurred in 41.8%, 34.7%, 36.5%, and 36.3% of patients on placebo, etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively.
  
  
  CONCLUSIONS
  Postoperative use of etoricoxib 90 and 120 mg in patients undergoing total knee replacement is both superior to placebo and non-inferior to ibuprofen in reducing pain at rest and also reduces opioid (morphine) consumption.
  
  
  BACKGROUND
  NCT00820027.
authors.affiliation: Department of Anaesthesiology and Intensive Care, Orebro University Hospital, Örebro, SE 701 85, Sweden. narendra.rawal@orebroll.se.
authors.forename: Narinder
authors.initials: N
authors.lastname: Rawal
authors.forename: Eugene
authors.initials: E
authors.lastname: Viscusi
authors.forename: Paul M
authors.initials: PM
authors.lastname: Peloso
authors.forename: Harold S
authors.initials: HS
authors.lastname: Minkowitz
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Sandhya
authors.initials: S
authors.lastname: Shah
authors.forename: Anish
authors.initials: A
authors.lastname: Mehta
authors.forename: Denesh K
authors.initials: DK
authors.lastname: Chitkara
authors.forename: Sean P
authors.initials: SP
authors.lastname: Curtis
authors.forename: Dimitris A
authors.initials: DA
authors.lastname: Papanicolaou
mesh_terms: D000368:Aged; D019645:Arthroplasty, Replacement, Knee; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage; D009294:Narcotics / Q000008:administration & dosage; D010149:Postoperative Pain / Q000188:drug therapy*; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D013450:Sulfones / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D009294:Narcotics; D011725:Pyridines; D013450:Sulfones; D009020:Morphine; D007052:Ibuprofen; D000077613:Etoricoxib