title: Safety and tolerability of high-dose intravenous esomeprazole for prevention of peptic ulcer rebleeding.
abstract: BACKGROUND
  Efficacy of a continuous high-dose intravenous infusion of esomeprazole, followed by an oral regimen after successful endoscopic therapy for peptic ulcer bleeding (PUB) was established in the PUB study (ClinicalTrials. gov identifier: NCT00251979). Mortality rates and detailed safety and tolerability results from this study are reported here.
  
  
  METHODS
  This was a double-blind, randomized study in patients ≥18 years with overt signs of upper gastrointestinal bleeding, following endoscopic diagnosis of a single gastric or duodenal ulcer (≥5 mm) with stigmata indicating current/ recent bleeding (Forrest class Ia, Ib, IIa, or IIb). Postendoscopic hemostasis, patients received intravenous esomeprazole (80 mg/30 minutes, then 8 mg/hour for 71.5 hours) or placebo. Postinfusion, all patients received open-label oral esomeprazole 40 mg once daily for 27 days. Mortality rates were analyzed using Fisher's exact test; other safety variables were analyzed descriptively.
  
  
  RESULTS
  A total of 767 patients were randomized; 764 comprised the safety analysis set (375 patients received esomeprazole, 389 placebo). Baseline characteristics were similar across the two treatment groups. Three deaths from the esomeprazole treatment group and eight from the placebo group occurred during the trial (0.8% versus 2.1%; P=0.22). From these 11 all-cause deaths, one (esomeprazole group; rebleeding from duodenal ulcer) occurred during the 72-hour intravenous treatment phase. Adverse event (AE) frequency was similar for the two groups over the intravenous treatment phase (esomeprazole, 39.2%; placebo, 41.9%), with gastrointestinal disorders being most commonly reported (12.3% and 19.8%, respectively). Serious AEs were mostly related to bleeding events. Infusion-site reactions (mild, transient) were reported in 4.3% of esomeprazole-treated patients versus 0.5% of placebo patients. These did not lead to treatment discontinuation.
  
  
  CONCLUSIONS
  Esomeprazole, given as a continuous high-dose intravenous infusion followed by an oral regimen after successful endoscopic therapy for PUB, was well tolerated, with no apparent safety concerns from either the high-dose intravenous treatment or oral phases.
authors.affiliation: Department of Gastroenterology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. e.j.kuipers@erasmusmc.nl
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Joseph J Y
authors.initials: JJ
authors.lastname: Sung
authors.forename: Alan
authors.initials: A
authors.lastname: Barkun
authors.forename: Joachim
authors.initials: J
authors.lastname: Mössner
authors.forename: Dennis
authors.initials: D
authors.lastname: Jensen
authors.forename: Robert
authors.initials: R
authors.lastname: Stuart
authors.forename: James Y W
authors.initials: JY
authors.lastname: Lau
authors.forename: Henrik
authors.initials: H
authors.lastname: Ahlbom
authors.forename: Tore
authors.initials: T
authors.lastname: Lind
authors.forename: Jan
authors.initials: J
authors.lastname: Kilhamn
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000359:Aftercare / Q000379:methods; D000368:Aged; D000369:Aged, 80 and over; D004304:Dosage Forms; D004311:Double-Blind Method; D064098:Esomeprazole / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016558:Hemostasis, Endoscopic; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D010437:Peptic Ulcer / Q000150:complications* / Q000401:mortality / Q000503:physiopathology; D010438:Peptic Ulcer Hemorrhage / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D054328:Proton Pump Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D055502:Secondary Prevention; D016896:Treatment Outcome
chemical_list: D004304:Dosage Forms; D054328:Proton Pump Inhibitors; D064098:Esomeprazole