Optimal Dose of Proton Pump Inhibitors Following an Upper Gastrointestinal Bleed

Study Overview
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Brief Summary
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Despite recommendations from clinical practice guidelines to discharge patients from the hospital on once daily proton pump inhibitors after acute management of UGIB, clinical practice is to use twice daily proton pump inhibitor therapy. The objective of this study will be to assess whether or not once daily pantoprazole is non-inferior to twice daily pantoprazole in ulcer healing with a dose of once daily versus twice daily proton-pump inhibitor following an upper gastrointestinal bleed. Additionally, this study will observe for any potential difference in safety for once daily versus twice daily proton pump inhibitors.

Detailed Description
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There are few clinical practice guidelines for the management of a non-variceal, upper gastrointestinal bleed (UGIB). The 2012 guidelines released by the American College of Gastroenterology (ACG) indicate that for active bleeding or non-bleeding visible vessels or adherent clot, a bolus of 80 mg proton pump inhibitor followed by continuous infusion of 8 mg/hr infusion is to be used. Following 72 hours of infusion therapy, an oral proton pump inhibitor (PPI) may be used. If the clot is a flat pigmented spot or a clean ulcer base, an oral proton pump inhibitor may be used for management (without infusion) (Laine 2012). There are no recommendations made on once versus twice daily proton pump inhibitor. The 2010 American College of Physicians guideline recommends following the 72-hour infusion with once-daily proton pump inhibitors for duration as dictated by underlying etiology following upper gastrointestinal bleeding (UGIB) (Barkun 2012). This recommendation is graded 1C, with the decision to support once-daily over twice-daily dosing due to demonstrated effective ulcer healing for patients with peptic ulcer disease with once-daily dosing, and insufficient data to suggest twice-daily is superior to once-daily. There have been no head-to-head trials to evaluate once-daily versus twice-daily proton pump inhibitor following acute management of an endoscopic bleed. Additionally, studies suggest about 50% to 60% of proton pump inhibitors are being used without appropriate indications or at inappropriate dosages (Ali 2009).Safety concerns such as increased risk for Clostridium difficile infection , community acquired pneumonia, electrolyte abnormalities (hypomagnesemia), and fractures are becoming more prevalent warranting improved risk versus benefit examination of proton pump inhibitors including ascertainment of least effective dosing (Ali 2009, Sheen 2011). Despite recommendations to discharge patients after acute management of UGIB on once daily PPI therapy, clinical practice is to use twice daily proton pump inhibitor therapy. The objective of this study will be to examine if once daily pantoprazole is non-inferior to twice daily pantoprazole with regards to ulcer healing after acute management of an UGIB. In addition, because more evidence is emerging regarding safety concerns with proton pump inhibitors, the study will seek to examine if once daily versus twice daily therapy results in difference in safety or adverse reactions such as occurrence of rebleed, C. difficile diarrhea, or pneumonia.

Official Title
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Optimal Dose of Proton Pump Inhibitors Following an Upper Gastrointestinal Bleed

Conditions
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Upper Gastrointestinal Bleed

Intervention / Treatment
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* Drug: Pantoprazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult, 18 years and older; Upper GI bleed confirmed by endoscopy Exclusion Criteria: Intensive Care Unit admission, Emergency endoscopic intervention required to control bleeding, Malignant appearing ulcers as determined by endoscopy, Previous documented treatment with twice daily PPI for other indication, Receiving twice daily PPI therapy prior to admission

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pantoprazole twice daily<br>Pantoprazole 40mg orally twice daily x 8 weeks after acute management of UGIB | Drug: Pantoprazole<br>* Pantoprazole 40mg orally daily x 8 weeks after acute management of UGIB<br>* Other names: Protonix;|
| Active Comparator: Pantoprazole once daily<br>Pantoprazole 40mg orally once daily x 8 weeks after acute management of UGIB | Drug: Pantoprazole<br>* Pantoprazole 40mg orally daily x 8 weeks after acute management of UGIB<br>* Other names: Protonix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ulcer Healing | as defined by follow-up endoscopy per gastroenterology service, 8 weeks after UGIB acute management | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Rebleed | Per patient report or as defined by follow-up endoscopy per gastroenterology service, 8 weeks after UGIB acute management High clinical suspicion of rebleed includes melena, hematochezia, confirmed by repeat endoscopy, requiring additional management | 8 weeks | 
| Clostridium Difficile Diarrhea | Clostridium difficile confirmed by polymerase chain reaction (PCR) | 8 weeks | 
| Community-Acquired Pneumonia | As defined by clinical suspicion and/or positive sputum culture requiring antibiotic treatment | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Proton pump inhibitor, Upper gastrointestinal bleed, Ulcer healing