Effect of IV and Oral Esomeprazole in Prevention of Recurrent Bleeding From Peptic Ulcers After Endoscopic Therapy (IOE)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Francis KL Chan, Chinese University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01142245
First received: June 9, 2010
Last updated: February 18, 2014
Last verified: February 2014
  Purpose

The investigators previously showed that the use of a high-dose intravenous PPI regimen after endoscopic control of bleeding from peptic ulcers reduced rate of recurrent bleeding, decreased the need for endoscopic and surgical interventions and in general improved patients' outcomes. A trend towards reduced mortality associated with the use of high-dose intravenous PPI was also observed. Recent clinical trials from Asia have provided evidence that high-dose oral PPIs are associated with a reduction in rebleeding. Current meta-analysis suggests that both high dose (intravenous) and low dose (oral) PPIs effectively reduce rebleeding vs placebo. However, there has been no clinical study to compare IV infusion to oral PPI in this patient population.

The purpose of this clinical study is to compare the efficacy and safety of intravenous and oral Esomeprazole in patients with peptic ulcer hemorrhage who are at risk for recurrent bleeding. The investigators hypothesize that using IV infusion is superior to oral PPI.


Condition Intervention Phase
Peptic Ulcer
Bleeding
Drug: Oral esomeprazole
Drug: Intravenous Esomeprazole
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase 3 Study of Effect of Intravenous and Oral Esomeprazole in Prevention of Recurrent Bleeding From Peptic Ulcers After Endoscopic Therapy (IOE Study)

Resource links provided by NLM:


Further study details as provided by Chinese University of Hong Kong:

Primary Outcome Measures:
  • Rate of clinical rebleeding within 30 day of endoscopic therapy [ Time Frame: 30 days ] [ Designated as safety issue: No ]

    Definition of clinical rebleeding

    1. Recurrent hematemesis
    2. fresh melena after normal stool
    3. Hypotension SBP<90 or tachycardia >110 AND fresh melena
    4. Decrease in Hb >2g/dL (or Hct > 10%) during any 24 h or an increas in Hb <1 g/dL (or Hct <3%) despite ≥4 units of blood has been transfused during any 48h


Secondary Outcome Measures:
  • Un-scheduled further endoscopic therapy [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    • Un-scheduled further endoscopic therapy
    • Need for surgery (i.e., operation rate)
    • Duration of hospitalization
    • Blood transfusion

  • Need for surgery [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Duration of hospitalization [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • Blood transfusion [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • mortality [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • need of surgery [ Time Frame: 30 days ] [ Designated as safety issue: No ]
  • un-scheduled further endoscopic therapy [ Time Frame: 30 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 406
Study Start Date: January 2008
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: oral esomeprazole
  • Esomeprazole placebo IV loading bolus
  • Esomeprazole placebo intravenous infusion for 72 hours
  • Oral Esomeprazole: 80 mg/Day on Day 1, 2 and Day 3, and the drug will be given as 40 mg q12h.
Drug: Oral esomeprazole
• Oral Esomeprazole 40mg on Day 1, 2 and Day 3 q12h
Other Names:
  • oral
  • nexium
Active Comparator: Intravenous Esomeprazole

Esomeprazole IV loading bolus 80mg

• Esomeprazole intravenous infusion 8mg/hr for 72 hours

Drug: Intravenous Esomeprazole

Esomeprazole IV 80mg loading bolus

  • Esomeprazole intravenous infusion 8mg/hr for 72 hours
Other Names:
  • IV
  • nexium

Detailed Description:

The investigators previously showed that the use of a high-dose intravenous PPI regimen after endoscopic control of bleeding from peptic ulcers reduced rate of recurrent bleeding, decreased the need for endoscopic and surgical interventions and in general improved patients' outcomes. A trend towards reduced mortality associated with the use of high-dose intravenous PPI was also observed. Recent clinical trials from Asia have provided evidence that high-dose oral PPIs are associated with a reduction in rebleeding. Current meta-analysis suggests that both high dose (intravenous) and low dose (oral) PPIs effectively reduce rebleeding vs placebo. However, there has been no clinical study to compare IV infusion to oral PPI in this patient population.

Endoscopic stigmata in bleeding peptic ulcers are prognostic and allow risk stratification. Patients with a clean ulcer base have a < 5% risk of rebleeding; this increases progressively with a flat spot, adherent clot, non-bleeding visible vessel and active bleeding (55%). Early endoscopy in patients with bleeding peptic ulcers selects the high risk ulcers for therapy and evaluation of adjuvant PPI use.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18
  • Confirmed ulcer bleeding with Forrest Ia, Ib, IIa, IIb
  • Endoscopic hemostasis achieved
  • Informed consent obtained

Exclusion Criteria:

  • No consent
  • Forrest II c, III (clear ulcer base/flat spot and no active bleeding, i.e., minimal risk for rebleeding)
  • Unsuccessful endoscopic treatment (i.e., injection and/or thermal coagulation for the initial bleeding) or severe bleeding that immediate surgery is indicated
  • Moribund patients in whom active treatment of any form is not considered.
  • Polytrauma, severe injury, unconsciousness, burns, or need for continuous artificial ventilation
  • Upper GI malignancy or disseminated malignant disease
  • Esophageal varices
  • A Mallory-Weiss lesion
  • Phenytoin or theophylline treatment
  • Uses of PPI or H2RAs within 3 days of admission, including uses at Emergency Department N.B. Usage of aspirin or NSAID is not an exclusion criteria.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01142245

Locations
China
Endoscopy Centre
Hong Kong, China, 852
Endoscopy Center in Prince of Wales Hospital
Hong Kong (SAR), China
Sponsors and Collaborators
Chinese University of Hong Kong
Investigators
Principal Investigator: Francis K Chan, MD CUHK
  More Information

No publications provided

Responsible Party: Francis KL Chan, professor, Chinese University of Hong Kong
ClinicalTrials.gov Identifier: NCT01142245     History of Changes
Other Study ID Numbers: IOE
Study First Received: June 9, 2010
Last Updated: February 18, 2014
Health Authority: Hong Kong: Department of Health

Keywords provided by Chinese University of Hong Kong:
ulcer bleeding
endoscopic therapy

Additional relevant MeSH terms:
Ulcer
Hemorrhage
Peptic Ulcer
Pathologic Processes
Duodenal Diseases
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Stomach Diseases
Esomeprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014