A randomised, double-blind, parallel-group, placebo controlled study of esomeprazole i.v. (bolus infusion of 80 mg followed by a continuous infusion of 8 mg per hour) administered for 72 hours to assess prevention of rebleeding in subjects that have undergone successful primary endoscopic haemostasis of a bleeding peptic ulcer – the PUB study - NA

INTERVENTION: Product Name: Nexium 40 mg powder for solution for injection/infusion Product Code: Esomeprazole powder for solution for injection/inf Pharmaceutical Form: Powder for infusion* INN or Proposed INN: Esomeprazole sodium CAS Number: 161796‐78‐7 Current Sponsor code: Esomeprazole sodium Other descriptive name: H 199/18 sodium Concentration unit: mg/g milligram(s)/gram Concentration type: equal Concentration number: 40‐ Pharmaceutical form of the placebo: Powder for solution for infusion Route of administration of the placebo: Intravenous use Product Name: Esomeprazole capsules 40 mg (unmarked capsules for clinical trial use) Product Code: Esomeprazole capsules 40 mg Pharmaceutical Form: Capsule, hard INN or Proposed INN: Esomeprazole magnesium trihydrate CAS Number: 217087‐09‐7 Current Sponsor code: Esomeprazole magnesium trihydrate Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 40‐ CONDITION: Gatrointestinal haemorrhages NEC. (Bleeding gastric or duodenal ulcer will be investigated). MedDRA classification code Level: HLGT = High Level Group Term. See below. ; MedDRA version: 8.0 Level: HLGT Classification code 10017959 PRIMARY OUTCOME: Main Objective: The primary objective is to compare, in subjects with PUB after successful endoscopic haemostasis, the efficacy of 72 hours continuous i.v. infusion of either esomeprazole or placebo by assessment of the rate of clinically significant rebleeding during the i.v. treatment period. Primary end point(s): There is no primary endpoint in this study.; ; Primary outcome variable: Clinically significant rebleeding within 72h of continues infusion of esomeprazole or placebo. Secondary Objective: To compare, in subjects with PUB after successful endoscopic haemostasis, 72 hours continuous i.v. infusion of either esomeprazole or placebo with regard to the following, where the time period begins at start of i.v. treatment:; 1. The rate of clinically significant rebleeding within 7 days and 30 days.; 2. Proportion of mortalities within 72 hours and 30 days.; 3. Rate of “bleed‐related” mortalities within 30 days, based on the assessments by the Endpoint Committee (EpC).; 4. Proportion of subjects who, within 72 hours and 30 days, had surgery (except endoscopic treatment) due to rebleeding.; 5. Proportion of subjects who within 72 hours and 30 days, had endoscopic re‐treatment due to rebleeding.; 6. Number of blood units transfused within 72 hours and 30 days.; 7. Number of days hospitalised due to rebleeding within 30 days.; 8. Safety and tolerability. ; In addition, the safety and tolerability of open oral treatment of esomeprazole 40 mg for 27 days will be assessed. INCLUSION CRITERIA: For inclusion in the study, subjects must fulfil all of the following criteria: 1. Provision of informed consent. 2. Female or male aged 18 years and over. 3. Upper gastrointestinal bleeding (haematemesis, melaena or haematochezia) or with such sign within the last 24 hours as judged by the investigator. 4. One endoscopically confirmed bleeding gastric or duodenal peptic ulcer, at least 5 mm in diameter, classified as Forrest Ia, Ib, IIa, or IIb. Photo documentation of the source of bleeding is required. Forrest classification of PUB (Forrest et al 1974): Ia = arterial bleeding Ib = oozing bleeding IIa = non‐bleeding visible vessel IIb = adherent clot In case of Forrest IIb (adherent clot), all efforts should be made to remove the clot. If the clot cannot be removed, it is to be handled as follows: ‐ If the clot can be removed with 5 min of high‐pressure water irrigation (Laine et al 1996) or by cold snare, the ulcer shou