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

Phase 3 Study of Effect of Intravenous and Oral Esomeprazole in Prevention of Recurrent Bleeding From Peptic Ulcers After Endoscopic Therapy (IOE Study)

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.

Study Overview

• Status: Completed
• Conditions: Bleeding; Peptic Ulcer
• Intervention / Treatment: Drug: Oral esomeprazole; Drug: Intravenous Esomeprazole

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.

• Study Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Hong Kong, China, 852
    • Endoscopy centre
  • Hong Kong (SAR), China
    • Endoscopy Center in Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of clinical rebleeding within 30 day of endoscopic therapy	Definition of clinical rebleeding; Recurrent hematemesis; fresh melena after normal stool; Hypotension SBP<90 or tachycardia >110 AND fresh melena; 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	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mortality		30 days
Duration of hospitalization		30 days
Un-scheduled further endoscopic therapy	Un-scheduled further endoscopic therapy; Need for surgery (i.e., operation rate); Duration of hospitalization; Blood transfusion	30 days
Need for surgery		30 days
Blood transfusion		30 days
need of surgery		30 days
un-scheduled further endoscopic therapy		30 days

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Francis K Chan, MD, CUHK

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: June 9, 2010
• First Submitted That Met QC Criteria: June 10, 2010
• First Posted (Estimate): June 11, 2010

Study Record Updates

• Last Update Posted (Estimate): August 13, 2015
• Last Update Submitted That Met QC Criteria: August 10, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: endoscopic therapy; ulcer bleeding
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Duodenal Diseases; Ulcer; Hemorrhage; Peptic Ulcer; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: IOE