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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01757275
First received: December 21, 2012
Last updated: February 9, 2016
Last verified: February 2016
  Purpose
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

Condition Intervention Phase
Bleeding Peptic Ulcer
Drug: Esomeprazole Na
Drug: Cimetidine
Drug: Esomeprazole Mg
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Rate of Clinically Significant Rebleeding Within 72 Hours [ Time Frame: 72 hours ] [ Designated as safety issue: No ]

    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:
  • Rate of Clinically Significant Rebleeding During 7 Days [ Time Frame: 7 days ] [ Designated as safety issue: No ]

    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.


  • Rate of Clinically Significant Rebleeding During 30 Days [ Time Frame: 30 days ] [ Designated as safety issue: No ]

    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 72 Hours [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Number of Patients With Endoscopic Re-treatment Within 30 Days [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Number of Patients With Surgery Due to Rebleeding Within 72 Hours [ Time Frame: within 72 hours ] [ Designated as safety issue: No ]
  • Number of Patients With Surgery Due to Rebleeding Within 30 Days [ Time Frame: within 30 days ] [ Designated as safety issue: No ]
  • Number of Blood Units Transfused Within 72 Hours [ Time Frame: within 72 hours ] [ Designated as safety issue: No ]
  • Number of Blood Units Transfused Within 30 Days [ Time Frame: within 30 days ] [ Designated as safety issue: No ]

Enrollment: 239
Study Start Date: February 2013
Study Completion Date: December 2014
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Esomeprazole Drug: Esomeprazole Na
Given as 80mg bolus infusion during 30 min and then 8mg/h constant infusion during 71.5 hous
Other Name: Nexium
Drug: Esomeprazole Mg
40 mg tablet once daily for 27 days
Other Name: Nexium
Active Comparator: Cimetidine Drug: Cimetidine
Given as 200mg bolus infusion during 30 min and then 60mg/h constant infusion during 71.5 hours

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
  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01757275

Locations
China
Research Site
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
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Tore Lind, MD AstraZeneca Molndal, Sweden
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01757275     History of Changes
Other Study ID Numbers: D961DC00007 
Study First Received: December 21, 2012
Results First Received: December 16, 2015
Last Updated: February 9, 2016
Health Authority: China: Food and Drug Administration

Keywords provided by AstraZeneca:
peptic ulcer bleeding
prevention of rebleeding
successful endoscopic haemostatic therapy

Additional relevant MeSH terms:
Ulcer
Hemorrhage
Peptic Ulcer
Peptic Ulcer Hemorrhage
Pathologic Processes
Duodenal Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Stomach Diseases
Gastrointestinal Hemorrhage
Esomeprazole
Cimetidine
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Histamine H2 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 24, 2016