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

NCT ID: NCT01142245

Last Updated: 2015-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 263 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2014-07-31

Brief 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.

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.

Conditions

Peptic Ulcer; Bleeding

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Oral esomeprazole

Intervention Type: DRUG

• Oral Esomeprazole 40mg on Day 1, 2 and Day 3 q12h

Intravenous Esomeprazole

Esomeprazole IV loading bolus 80mg

• Esomeprazole intravenous infusion 8mg/hr for 72 hours

Group Type: ACTIVE_COMPARATOR

Intravenous Esomeprazole

Intervention Type: DRUG

Esomeprazole IV 80mg loading bolus

• Esomeprazole intravenous infusion 8mg/hr for 72 hours

Interventions

Oral esomeprazole

• Oral Esomeprazole 40mg on Day 1, 2 and Day 3 q12h

Intervention Type: DRUG

Intravenous Esomeprazole

Esomeprazole IV 80mg loading bolus

• Esomeprazole intravenous infusion 8mg/hr for 72 hours

Intervention Type: DRUG

Other Intervention Names

oral; nexium; IV; nexium

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chinese University of Hong Kong

OTHER

Sponsor Role: lead

Responsible Party

Francis KL Chan

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Francis K Chan, MD

Role: PRINCIPAL_INVESTIGATOR

CUHK

Locations

Endoscopy Centre

Hong Kong, , China

Endoscopy Center in Prince of Wales Hospital

Hong Kong (sar), , China

Countries

China

Other Identifiers

IOE

Identifier Type: -

Identifier Source: org_study_id