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

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Bleeding Peptic Ulcer

Intervention / Treatment
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* Drug: Esomeprazole Na
* Drug: Cimetidine
* Drug: Esomeprazole Mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Number of Blood Units Transfused Within 30 Days |  | within 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peptic ulcer bleeding, prevention of rebleeding, successful endoscopic haemostatic therapy