Deprescribing Proton Pump Inhibitors to Reduce Post-TIPS Hepatic Encephalopathy

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized Open-label Trial of Deprescribing Proton Pump Inhibitors to Reduce the Risk of Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt Creation

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Drug: PPI deprescribing


Participation Criteria
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Eligibility Criteria
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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

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PPI deprescribing arm<br>Patients taking a PPI (at least 20 mg omeprazole equivalent daily) will be instructed to stop taking their PPI. | Drug: PPI deprescribing<br>* 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.<br>|
| No Intervention: PPI continuation arm<br>Patients will be instructed to continue taking their PPI (at least 20 mg omeprazole equivalent daily) as usual. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimal hepatic encephalopathy | Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score | Approximately 6-8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Per-protocol evaluation of minimal hepatic encephalopathy | Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score, based on actual reported PPI use | Approximately 6-8 weeks | 
| Chronic liver disease specific quality of life | Chronic liver disease (CLDQ) specific QOL assessment | Approximately 6-8 weeks | 
| Gastroesophageal reflux specific quality of life | Gastroesophageal reflux (QOLRAD) specific QOL assessment | Approximately 6-8 weeks | 
| Overt hepatic encephalopathy | Episodes of overt hepatic encephalopathy (defined as West-Haven grade 2 or greater) | Approximately 6-8 weeks | 
| 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 | Approximately 6-8 weeks | 
| Adverse events | Adverse events in the PPI continuation versus discontinuation arms | Approximately 6-8 weeks |