Optimal Dose of Proton Pump Inhibitors Following an Upper Gastrointestinal Bleed

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 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 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.

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