High Dose Esomeprazole Na for Prevention of Rebleeding After Successful Endoscopic Therapy of a Bleeding Peptic Ulcer

Phase 3

Completed

Conditions: Bleeding Peptic Ulcer

Interventions: Drug: Cimetidine
Drug: Esomeprazole Na
Drug: Esomeprazole Mg

Registration Number: NCT01757275

Lead Sponsor: AstraZeneca

Brief Summary: To describe the rate of clinically significant rebleeding during 72 hours continuous i.v. infusion of high dose esomeprazole Na in patients in China with primary successful endoscopic haemostatic therapy of a bleeding peptic ulcer, with cimetidine i.v. in

Detailed Description: A multi-center, randomised, double-blind, parallel-group phase III study to assess high dose esomeprazole Na i.v. treatment (bolus infusion of 80 mg followed by a continuous infusion of 8 mg per hour administered for 72 hours) for prevention of rebleeding

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 239

Inclusion Criteria

Provision of informed consent prior to any study specific procedures.
Female or male aged =18 years and =70 years.
Acute upper gastrointestinal bleeding (haematemesis, melaena or haematochezia) or such signs within the last 24 hours as judged by the investigator.
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 should be provided.
Successful haemostasis (which is considered to have been established if bleeding has stopped and, if applicable, formerly bleeding vessels are flattened or cavitated) achieved by endoscopic treatment and confirmed by site staff.

Exclusion Criteria

Endoscopic suspicion of gastric malignancy or juxta pyloric stenosis as judged by the investigator.
Sign of multi PUB or concomitant other gastro bleeding from esophageal varices, reflux esophagitis, gastritis, Mallory Weiss rifts, ulcus simplex, Dieulafoy's lesion, colon, small bowel, or ulcer distal to the stom in Billroth-resected patients.
Need for treatment during the first 7 days of the study with NSAIDs, Cyclooxygenase-2 (COX-2) inhibitors, acetyl salicylic acid (ASA) (including low dose) or clopidogrel.
Planned treatment with: warfarin (including other vitamin K antagonists), cisapride, phenytoin, atazanavir, nelfinavir, digoxin, methotrexate, clopidogrel, tacrolimus, theophylline, lidocaine, nifedipine.
Chemotherapy or radiation therapies within 2 weeks prior to randomisation or planned during the course of the study.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cimetidine	Cimetidine	-
Esomeprazole	Esomeprazole Na	-
Esomeprazole	Esomeprazole Mg	-

Primary Outcome Measures

Name	Time	Method
Rate of Clinically Significant Rebleeding Within 72 Hours	72 hours	Diagnostic criteria for clinically significant rebleeding based on either A, B or C: A) Endoscopy - initiated by clinical signs of bleeding defined as one of B1 or B2 or B3 and endoscopic verification, ie one of A1 or A2. A1: Blood in stomach (this criteria cannot be used during the first 6 hours after primary endoscopic haemostasis). A2: A verified active bleeding from a peptic ulcer (Forrest Ia, Ib). B) A true clinically based definition, at least two of B1 and/or B2 and/or B3. B1: Vomiting of fresh blood or fresh blood in a gastric tube or haematochezia or melaena after a normal stool. B2: Decrease in Hb \>20g/L (or Hct \>6%) during 24 hours or an increase in Hb \<10g/L (or Hct \<3%) despite ≥2 units of blood has been transfused during 24hours. B3: Unstable circulation systolic blood pressure ≤ 90 mmHg or pulse ≥110/min (after have had a stable circulation). C) Haematemesis. Vomiting significant amounts (\>200 ml) of fresh blood as estimated by the investigator.

Secondary Outcome Measures

Name	Time	Method
Number of Patients With Surgery Due to Rebleeding Within 30 Days	within 30 days
Number of Blood Units Transfused Within 72 Hours	within 72 hours
Number of Blood Units Transfused Within 30 Days	within 30 days
Rate of Clinically Significant Rebleeding During 7 Days	7 days	Diagnostic criteria for clinically significant rebleeding based on either A, B or C: A) Endoscopy - initiated by clinical signs of bleeding defined as one of B1 or B2 or B3 and endoscopic verification, ie one of A1 or A2. A1: Blood in stomach (this criteria cannot be used during the first 6 hours after primary endoscopic haemostasis). A2: A verified active bleeding from a peptic ulcer (Forrest Ia, Ib). B) A true clinically based definition, at least two of B1 and/or B2 and/or B3. B1: Vomiting of fresh blood or fresh blood in a gastric tube or haematochezia or melaena after a normal stool. B2: Decrease in Hb \>20g/L (or Hct \>6%) during 24 hours or an increase in Hb \<10g/L (or Hct \<3%) despite ≥2 units of blood has been transfused during 24hours. B3: Unstable circulation systolic blood pressure ≤ 90 mmHg or pulse ≥110/min (after have had a stable circulation). C) Haematemesis. Vomiting significant amounts (\>200 ml) of fresh blood as estimated by the investigator.
Number of Patients With Surgery Due to Rebleeding Within 72 Hours	within 72 hours
Number of Patients With Endoscopic Re-treatment Within 72 Hours	72 hours
Rate of Clinically Significant Rebleeding During 30 Days	30 days	Diagnostic criteria for clinically significant rebleeding based on either A, B or C: A) Endoscopy - initiated by clinical signs of bleeding defined as one of B1 or B2 or B3 and endoscopic verification, ie one of A1 or A2. A1: Blood in stomach (this criteria cannot be used during the first 6 hours after primary endoscopic haemostasis). A2: A verified active bleeding from a peptic ulcer (Forrest Ia, Ib). B) A true clinically based definition, at least two of B1 and/or B2 and/or B3. B1: Vomiting of fresh blood or fresh blood in a gastric tube or haematochezia or melaena after a normal stool. B2: Decrease in Hb \>20g/L (or Hct \>6%) during 24 hours or an increase in Hb \<10g/L (or Hct \<3%) despite ≥2 units of blood has been transfused during 24hours. B3: Unstable circulation systolic blood pressure ≤ 90 mmHg or pulse ≥110/min (after have had a stable circulation). C) Haematemesis. Vomiting significant amounts (\>200 ml) of fresh blood as estimated by the investigator.
Number of Patients With Endoscopic Re-treatment Within 30 Days	30 days