Deprescribing Proton Pump Inhibitors to Reduce Post-TIPS Hepatic Encephalopathy
Primary Purpose
Hepatic Encephalopathy
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PPI deprescribing
Sponsored by
About this trial
This is an interventional prevention trial for Hepatic Encephalopathy
Eligibility Criteria
Inclusion Criteria:
- Undergoing TIPS creation as part of routine clinical care
- On PPIs therapy (at least 20 mg omeprazole equivalent daily)
- Provision of signed and dated informed consent form by participant or legal representative
- Stated willingness to comply with all study procedures and availability for the duration of the study
- Male or female, age greater or equal to 18
Exclusion Criteria:
- Grade IV esophagitis or gastric or duodenal ulcer
- Recent endoscopic esophageal variceal band ligation necessitating PPI therapy for prevention of banding ulcer
- Zollinger-Ellison syndrome
- Active Helicobacter pylori infection
- Pregnancy
Sites / Locations
- Duke University HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
PPI deprescribing arm
PPI continuation arm
Arm Description
Patients taking a PPI (at least 20 mg omeprazole equivalent daily) will be instructed to stop taking their PPI.
Patients will be instructed to continue taking their PPI (at least 20 mg omeprazole equivalent daily) as usual.
Outcomes
Primary Outcome Measures
Minimal hepatic encephalopathy
Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score
Secondary Outcome Measures
Per-protocol evaluation of minimal hepatic encephalopathy
Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score, based on actual reported PPI use
Chronic liver disease specific quality of life
Chronic liver disease (CLDQ) specific QOL assessment
Gastroesophageal reflux specific quality of life
Gastroesophageal reflux (QOLRAD) specific QOL assessment
Overt hepatic encephalopathy
Episodes of overt hepatic encephalopathy (defined as West-Haven grade 2 or greater)
On-demand requirement for acid suppression therapy
Proportion of patients in the PPI discontinuation arm needing on-demand H2 blockers or PPIs for gastroesophageal reflux symptoms
Adverse events
Adverse events in the PPI continuation versus discontinuation arms
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05070351
Brief Title
Deprescribing Proton Pump Inhibitors to Reduce Post-TIPS Hepatic Encephalopathy
Official Title
A Randomized Open-label Trial of Deprescribing Proton Pump Inhibitors to Reduce the Risk of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt Creation
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 3, 2022 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
A total of 40 patients taking proton pump inhibitors (PPIs) who undergo transjugular intrahepatic portosystemic shunt (TIPS) creation as part of routine clinical care will be randomized in 1:1 fashion to either continue or discontinue their PPIs to determine whether these commonly used gastric acid suppressing agents increase risk of post-TIPS hepatic encephalopathy (HE). Patients will be assessed for symptoms of minimal HE (MHE), using the established psychometric hepatic encephalopathy score (PHES) battery of tests. MHE assessment will be conducted at two timepoints: at baseline prior to randomization and TIPS creation and approximately 4 weeks after randomization and TIPS creation. Stool samples will also be collected at both timepoints to allow characterization of the gastrointestinal (GI) tract microbiome using 16S rRNA sequencing. The pre to post-TIPS change in PHES scores will be compared between patients randomized to continue versus discontinue their PPIs. Quality of life (QOL) will also be assessed. Changes in the GI tract microbiome will be analyzed to determine whether this represents a potential biological mechanism linking PPI use with post-TIPS HE.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Encephalopathy
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
PPI deprescribing arm
Arm Type
Experimental
Arm Description
Patients taking a PPI (at least 20 mg omeprazole equivalent daily) will be instructed to stop taking their PPI.
Arm Title
PPI continuation arm
Arm Type
No Intervention
Arm Description
Patients will be instructed to continue taking their PPI (at least 20 mg omeprazole equivalent daily) as usual.
Intervention Type
Drug
Intervention Name(s)
PPI deprescribing
Intervention Description
Patients currently on a proton pump inhibitor (PPI) undergoing transjugular intrahepatic portosystemic shunt (TIPS) creation as part of routine clinical care will be randomized to receive instructions to stop taking their PPI.
Primary Outcome Measure Information:
Title
Minimal hepatic encephalopathy
Description
Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score
Time Frame
Approximately 6-8 weeks
Secondary Outcome Measure Information:
Title
Per-protocol evaluation of minimal hepatic encephalopathy
Description
Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score, based on actual reported PPI use
Time Frame
Approximately 6-8 weeks
Title
Chronic liver disease specific quality of life
Description
Chronic liver disease (CLDQ) specific QOL assessment
Time Frame
Approximately 6-8 weeks
Title
Gastroesophageal reflux specific quality of life
Description
Gastroesophageal reflux (QOLRAD) specific QOL assessment
Time Frame
Approximately 6-8 weeks
Title
Overt hepatic encephalopathy
Description
Episodes of overt hepatic encephalopathy (defined as West-Haven grade 2 or greater)
Time Frame
Approximately 6-8 weeks
Title
On-demand requirement for acid suppression therapy
Description
Proportion of patients in the PPI discontinuation arm needing on-demand H2 blockers or PPIs for gastroesophageal reflux symptoms
Time Frame
Approximately 6-8 weeks
Title
Adverse events
Description
Adverse events in the PPI continuation versus discontinuation arms
Time Frame
Approximately 6-8 weeks
Other Pre-specified Outcome Measures:
Title
Change in gastrointestinal tract microbiome
Description
Pre-TIPS to post-TIPS change in stool taxon abundances as measured by 16S rRNA sequencing
Time Frame
Approximately 6-8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Undergoing TIPS creation as part of routine clinical care
On PPIs therapy (at least 20 mg omeprazole equivalent daily)
Provision of signed and dated informed consent form by participant or legal representative
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, age greater or equal to 18
Exclusion Criteria:
Grade IV esophagitis or gastric or duodenal ulcer
Recent endoscopic esophageal variceal band ligation necessitating PPI therapy for prevention of banding ulcer
Zollinger-Ellison syndrome
Active Helicobacter pylori infection
Pregnancy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
James Ronald, MD PhD
Phone
919-684-7299
Email
james.ronald@duke.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Ronald, MD PhD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Hospital
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Clinical Research Coordinator
Phone
919-684-7810
Email
latonia.strader@duke.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Deprescribing Proton Pump Inhibitors to Reduce Post-TIPS Hepatic Encephalopathy
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