A Comparison of Gastric pH Control With High Dose Intravenous or Oral Esomeprazole

Study Overview
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Brief Summary
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The investigators hypothesize that high dose esomeprazole 80mg given as a bolus, followed by 8mg/h would render gastric pH near neutral and that pH control with esomeprazole given in such a high dose either intravenous or orally is identical.

Detailed Description
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Bleeding peptic ulcer is a common and life threatening condition. Endoscopic therapy has become the mainstay of controlling bleeding. Recurrent bleeding after endoscopic control occurs in about 20% of patients with a high associated mortality. We previously demonstrated that the adjunct use of high dose proton pump inhibitor reduces risk of recurrent bleeding and thereby improves patients' outcome [Lau JY N Engl J Med 2000]. The newer PPI, esomeprazole, is an S-isomer of omeprazole. Esomeprazole is more effective in gastric acid control as measured by both basal and pentagastrin acid output when compared to omeprazole. Esomeprazole when given orally at a lower dose achieves a similar gastric control than intravenous esomeprazole. The gastric pH with a high dose esomeprazole when given either orally or intravenously has not been measured among Hong Kong Chinese. If a high dose oral esomeprazole achieves a similar pH control near gastric neutrality, the oral regime can be used in place of the intravenous formulation. This represents significant convenience in dosing and cost savings.

Official Title
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A Randomized Comparison of High Dose Oral to Intravenous Esomeprazole in Patients After Endoscopic Control to Their Bleeding Peptic Ulcers: an Intra-gastric pH Study.

Conditions
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Gastrointestinal Hemorrhage

Intervention / Treatment
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* Drug: Intravenous bolus injection of esomeprazole
* Drug: Oral esomeprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients admitted with diagnosis of upper gastrointestinal bleeding aged between 18 and 80 Endoscopic confirmation of a bleeding duodenal or gastric ulcer to which endoscopic control has been obtained Absence of H. pylori infection Informed written consent Exclusion Criteria: Known incompatibility to the study drugs; Known incompatibility and hypersensitivity to proton pump inhibitor H. pylori infection Recent H2RA or PPI use (within last 4 weeks) Concomitant use of medications that may interfere gastric acid secretion or motility (e.g. anticholinergic, metoclopramide, domperidone) Pregnancy or lactation; Non-compliance e.g. mental subordination Nasopharyngeal or oropharyngeal pathology that would prevent passage of a nasal catheter Significant liver disease as PPI is metabolized by the cytochrome P-450 system Previous gastric surgery Chronic Aspirin user Presence of esophageal/ gastric varices Moribund patients, terminal malignancy & patients with severe renal disease Patient unable to give written consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IV Nexium<br>Intravenous bolus injection of esomeprazole (Astra Pharmaceutica AG, Dietikon, Switzerland) 80mg followed by continuous intravenous infusion of 8mg per hour for 24 hours | Drug: Intravenous bolus injection of esomeprazole<br>* 80mg followed by continuous intravenous infusion of 8mg per hour for 24 hours<br>* Other names: IV Nexium;|
| Active Comparator: Oral Nexium<br>Oral esomeprazole (Astra Pharmaceutica AG, Dietikon, Switzerland) 40mg every 12 hours for 24 hours | Drug: Oral esomeprazole<br>* 40mg every 12 hours for 24 hours<br>* Other names: Oral Nexium;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary measure of this study is the median gastric pH over 24-hour monitoring. |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| acid suppressing activity, notably the rate of onset of action, between the two treatment regimens: 1. Percentage time of pH<6 2. Time to reach pH 6 3. Median gastric pH in the first 6 and 12 hours |  | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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24 hours pH monitoring