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

Bleeding Clinical Trial

— IOE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01142245
• Other study ID #: IOE
• Status: Completed
• Phase: Phase 3
• First received: June 9, 2010
• Last updated: August 10, 2015
• Start date: January 2008
• Est. completion date: July 2014

Study information

• Verified date: August 2015
• Source: Chinese University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hong Kong: Department of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 263
• Est. completion date: July 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bleeding
• Hemorrhage
• Peptic Ulcer
• Ulcer

Intervention

Drug:
• Oral esomeprazole
• Oral Esomeprazole 40mg on Day 1, 2 and Day 3 q12h
• Intravenous Esomeprazole
Esomeprazole IV 80mg loading bolus Esomeprazole intravenous infusion 8mg/hr for 72 hours

Locations

Country	Name	City	State
China	Endoscopy Centre	Hong Kong
China	Endoscopy Center in Prince of Wales Hospital	Hong Kong (SAR)

Sponsors (1)

Lead Sponsor	Collaborator
Chinese University of Hong Kong

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Un-scheduled further endoscopic therapy	Un-scheduled further endoscopic therapy; Need for surgery (i.e., operation rate); Duration of hospitalization; Blood transfusion	30 days	No
Secondary	Need for surgery		30 days	No
Secondary	Duration of hospitalization		30 days	No
Secondary	Blood transfusion		30 days	No
Secondary	mortality		30 days	No
Secondary	need of surgery		30 days	No
Secondary	un-scheduled further endoscopic therapy		30 days	No