Optimal Dose of Proton Pump Inhibitors Following an Upper Gastrointestinal Bleed

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ClinicalTrials.gov Identifier: NCT02235311

Recruitment Status : Terminated (Difficulty recruiting and consenting participants)

First Posted : September 9, 2014

Results First Posted : July 2, 2017

Last Update Posted : July 31, 2017

Sponsor:

Information provided by (Responsible Party):

University of Missouri-Columbia

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Upper Gastrointestinal Bleed	Drug: Pantoprazole	Not Applicable

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	3 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Optimal Dose of Proton Pump Inhibitors Following an Upper Gastrointestinal Bleed
Study Start Date :	October 2014
Actual Primary Completion Date :	August 17, 2015
Actual Study Completion Date :	August 17, 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bleeding Gastrointestinal Bleeding

Drug Information available for: Pantoprazole Pantoprazole sodium

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Pantoprazole twice daily Pantoprazole 40mg orally twice daily x 8 weeks after acute management of UGIB	Drug: Pantoprazole Pantoprazole 40mg orally daily x 8 weeks after acute management of UGIB Other Name: Protonix
Active Comparator: Pantoprazole once daily Pantoprazole 40mg orally once daily x 8 weeks after acute management of UGIB	Drug: Pantoprazole Pantoprazole 40mg orally daily x 8 weeks after acute management of UGIB Other Name: Protonix

Outcome Measures

Primary Outcome Measures :

Ulcer Healing [ Time Frame: 8 weeks ]
as defined by follow-up endoscopy per gastroenterology service, 8 weeks after UGIB acute management

Secondary Outcome Measures :

Rate of Rebleed [ Time Frame: 8 weeks ]
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
Clostridium Difficile Diarrhea [ Time Frame: 8 weeks ]
Clostridium difficile confirmed by polymerase chain reaction (PCR)
Community-Acquired Pneumonia [ Time Frame: 8 weeks ]
As defined by clinical suspicion and/or positive sputum culture requiring antibiotic treatment

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02235311

Locations

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United States, Missouri
University Hospital
Columbia, Missouri, United States, 65112

Sponsors and Collaborators

University of Missouri-Columbia

Investigators

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Principal Investigator:	Ashley M Ausmus, Pharm.D.	University of Missouri-Health Care

More Information

Publications:

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. Review.

Massó González EL, García Rodríguez 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.

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. Review.

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. Review.

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.

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. Review.

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Responsible Party:	University of Missouri-Columbia
ClinicalTrials.gov Identifier:	NCT02235311
Other Study ID Numbers:	1212917
First Posted:	September 9, 2014 Key Record Dates
Results First Posted:	July 2, 2017
Last Update Posted:	July 31, 2017
Last Verified:	June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by University of Missouri-Columbia:


Proton pump inhibitor Upper gastrointestinal bleed Ulcer healing

Additional relevant MeSH terms:

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Gastrointestinal Hemorrhage Hemorrhage Pathologic Processes Gastrointestinal Diseases Digestive System Diseases Pantoprazole	Anti-Ulcer Agents Gastrointestinal Agents Proton Pump Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

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