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

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

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

Study Overview

• Status: Completed
• Conditions: Bleeding Peptic Ulcer
• Intervention / Treatment: Drug: Esomeprazole Na; Drug: Esomeprazole Mg; Drug: Cimetidine

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

• Study Type: Interventional
• Enrollment (Actual): 239
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Research Site
  • Changsha, China
    • Research Site
  • Chongqing, China
    • Research Site
  • Guangzhou, China
    • Research Site
  • Ha'er bing, China
    • Research Site
  • Hangzhou, China
    • Research Site
  • Ji Nan, China
    • Research Site
  • Nanchang, China
    • Research Site
  • Nanjing, China
    • Research Site
  • Shanghai, China
    • Research Site
  • Wuhan, China
    • Research Site
  • Xian, China
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Cimetidine	Drug: Cimetidine; Given as 200mg bolus infusion during 30 min and then 60mg/h constant infusion during 71.5 hours
Experimental: Esomeprazole	Drug: Esomeprazole Na; Given as 80mg bolus infusion during 30 min and then 8mg/h constant infusion during 71.5 hous; Other Names: Nexium; Drug: Esomeprazole Mg; 40 mg tablet once daily for 27 days; Other Names: Nexium

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Clinically Significant Rebleeding Within 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.	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Blood Units Transfused Within 30 Days		within 30 days
Rate of Clinically Significant Rebleeding During 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.	7 days
Rate of Clinically Significant Rebleeding During 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.	30 days
Number of Patients With Endoscopic Re-treatment Within 72 Hours		72 hours
Number of Patients With Endoscopic Re-treatment Within 30 Days		30 days
Number of Patients With Surgery Due to Rebleeding Within 72 Hours		within 72 hours
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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Tore Lind, MD, AstraZeneca Mölndal, Sweden

Publications and helpful links

General Publications

• Bai Y, Chen DF, Wang RQ, Chen YX, Shi RH, Tian DA, Chen H, Eklund S, Li ZS; Chinese Peptic Ulcer Bleeding Research Group. Intravenous Esomeprazole for Prevention of Peptic Ulcer Rebleeding: A Randomized Trial in Chinese Patients. Adv Ther. 2015 Nov;32(11):1160-76. doi: 10.1007/s12325-015-0265-6. Epub 2015 Nov 18.

Helpful Links

• China_PUB_Study_D961DC00007_Clinical_Study_Protocol_GEL_Redacted_(approved)

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: December 21, 2012
• First Submitted That Met QC Criteria: December 21, 2012
• First Posted (Estimate): December 28, 2012

Study Record Updates

• Last Update Posted (Estimate): March 8, 2016
• Last Update Submitted That Met QC Criteria: February 9, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: peptic ulcer bleeding; prevention of rebleeding; successful endoscopic haemostatic therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Duodenal Diseases; Gastrointestinal Hemorrhage; Ulcer; Hemorrhage; Peptic Ulcer; Peptic Ulcer Hemorrhage; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Cytochrome P-450 Enzyme Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Histamine Antagonists; Histamine Agents; Cytochrome P-450 CYP1A2 Inhibitors; Histamine H2 Antagonists; Esomeprazole; Cimetidine
• Other Study ID Numbers: D961DC00007