title: Less small-bowel injury with lumiracoxib compared with naproxen plus omeprazole.
abstract: OBJECTIVE
  The selective cyclooxygenase-2 inhibitor lumiracoxib has been shown to reduce endoscopically detected ulcers and ulcer complications in the upper gastrointestinal tract compared with nonselective nonsteroidal anti-inflammatory drugs. We investigated whether lumiracoxib would reduce small-bowel injury compared with naproxen plus omeprazole.
  
  
  METHODS
  Healthy volunteers were randomized to receive lumiracoxib 100 mg once daily, naproxen 500 mg twice daily plus omeprazole 20 mg once daily, or placebo in a 16-day double-blind, parallel-group study. Small-bowel mucosal injury and inflammation were assessed by video capsule endoscopy, the lactulose:L-rhamnose permeability assessment, and the fecal calprotectin test.
  
  
  RESULTS
  Of 152 randomized subjects, 139 completed the study with valid video capsule endoscopies (lumiracoxib, n = 47; naproxen plus omeprazole, n = 45; placebo, n = 47). Compared with placebo, an increased number of subjects on naproxen plus omeprazole had small-bowel mucosal breaks (77.8% vs 40.4%, P < .001), with increased permeability (P = .023) and increased fecal calprotectin (increase, 96.8 vs 14.5 mg/kg for placebo; P < .001). With lumiracoxib, 27.7% of subjects had small-bowel mucosal breaks (P = .196 vs placebo; P < .001 vs naproxen), there was no increase in permeability (P = .157 vs placebo; P = .364 vs naproxen), and no increase in fecal calprotectin (-5.7 mg/kg; P = .377 vs placebo; P < .001 vs naproxen).
  
  
  CONCLUSIONS
  As assessed by 3 different measures, acute small-bowel injury on lumiracoxib treatment is less frequent than with naproxen plus omeprazole and similar to placebo.
authors.affiliation: Wolfson Digestive Diseases Centre, University Hospital, Nottingham, United Kingdom. cj.hawkey@nottingham.ac.uk
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hawkey
authors.forename: Christian
authors.initials: C
authors.lastname: Ell
authors.forename: Bernd
authors.initials: B
authors.lastname: Simon
authors.forename: Jörg
authors.initials: J
authors.lastname: Albert
authors.forename: Martin
authors.initials: M
authors.lastname: Keuchel
authors.forename: Mark
authors.initials: M
authors.lastname: McAlindon
authors.forename: Paul
authors.initials: P
authors.lastname: Fortun
authors.forename: Stefan
authors.initials: S
authors.lastname: Schumann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bolten
authors.forename: Anthony
authors.initials: A
authors.lastname: Shonde
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Hugot
authors.forename: Vincent
authors.initials: V
authors.lastname: Yu
authors.forename: Udayasankar
authors.initials: U
authors.lastname: Arulmani
authors.forename: Gerhard
authors.initials: G
authors.lastname: Krammer
authors.forename: Rosemary
authors.initials: R
authors.lastname: Rebuli
authors.forename: Ervin
authors.initials: E
authors.lastname: Toth
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D053705:Capsule Endoscopes; D018592:Cross-Over Studies; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D016099:Endoscopy, Gastrointestinal / Q000379:methods; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007421:Intestine, Small / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000008:administration & dosage / Q000009:adverse effects*; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects*; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D014456:Ulcer / Q000139:chemically induced* / Q000473:pathology
chemical_list: D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac; D009288:Naproxen; D009853:Omeprazole; C473384:lumiracoxib