Clinical trial NCT02235311: Optimal Dose of Proton Pump Inhibitors Following an Upper Gastrointestinal Bleed
Official title: Optimal Dose of Proton Pump Inhibitors Following an Upper Gastrointestinal Bleed
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Upper Gastrointestinal Bleed
Keywords: Proton pump inhibitor
Upper gastrointestinal bleed
Ulcer healing
Lead sponsor: University of Missouri-Columbia
Sponsor class: OTHER
First posted: 2014-09-09
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Ulcer Healing
timeFrame: 8 weeks
Secondary outcomes:
measure: Rate of Rebleed
timeFrame: 8 weeks
measure: Clostridium Difficile Diarrhea
timeFrame: 8 weeks
measure: Community-Acquired Pneumonia
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Columbia
country: United States
facility: University Hospital
state: Missouri
Study officials:
affiliation: University of Missouri-Health Care
name: Ashley M Ausmus, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ali T, Roberts DN, Tierney WM. Long-term safety concerns with proton pump inhibitors. Am J Med. 2009 Oct;122(10):896-903. doi: 10.1016/j.amjmed.2009.04.014.
citation: Masso Gonzalez EL, Garcia Rodriguez LA. Proton pump inhibitors reduce the long-term risk of recurrent upper gastrointestinal bleeding: an observational study. Aliment Pharmacol Ther. 2008 Sep 1;28(5):629-37. doi: 10.1111/j.1365-2036.2008.03780.x. Epub 2008 Jun 26.
citation: Holster IL, Kuipers EJ. Management of acute nonvariceal upper gastrointestinal bleeding: current policies and future perspectives. World J Gastroenterol. 2012 Mar 21;18(11):1202-7. doi: 10.3748/wjg.v18.i11.1202.
citation: Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol. 2012 Mar;107(3):345-60; quiz 361. doi: 10.1038/ajg.2011.480. Epub 2012 Feb 7.
citation: Barkun AN, Bardou M, Kuipers EJ, Sung J, Hunt RH, Martel M, Sinclair P; International Consensus Upper Gastrointestinal Bleeding Conference Group. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010 Jan 19;152(2):101-13. doi: 10.7326/0003-4819-152-2-201001190-00009.
citation: Sheen E, Triadafilopoulos G. Adverse effects of long-term proton pump inhibitor therapy. Dig Dis Sci. 2011 Apr;56(4):931-50. doi: 10.1007/s10620-010-1560-3. Epub 2011 Mar 2.