Deprescribing Proton Pump Inhibitors to Reduce Post-TIPS Hepatic Encephalopathy

Duke University33 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Enrollment

Conditions

Hepatic Encephalopathy

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change in Minimal Hepatic Encephalopathy

Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score (PHES). Reported as the number of mistakes on line tracing test after TIPS compared to baseline (possible values range from - infinity to + infinity). Higher numbers indicate more errors.

Time frame: Baseline (before transjugular intrahepatic portosystemic shunt - TIPS), after TIPS (approximately 6-8 weeks)

Secondary Outcomes

Change in Per-protocol Evaluation of Minimal Hepatic Encephalopathy

Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score, based on actual reported PPI (Proton Pump Inhibitors) use. Reported as the number of mistakes on line tracing test after TIPS compared to baseline (possible values range from - infinity to + infinity). Higher numbers indicate more errors.

Time frame: Baseline (before TIPS), after TIPS (approximately 6-8 weeks)

Change in Chronic Liver Disease Specific Quality of Life (CLDQ)

Chronic liver disease (CLDQ) specific QOL assessment. Reported as the score difference after TIPS compared to baseline (possible range -174 to +174). Higher numbers indicate worse quality of life.

Time frame: Baseline (TIPS), after TIPS (approximately 6-8 weeks)

Change in Gastroesophageal Reflux Specific Quality of Life

Gastroesophageal reflux (QOLRAD) specific QOL assessment. Reported as the score difference after TIPS compared to baseline (possible range -150 to +150). Higher numbers indicate worse quality of life.

Time frame: Baseline (TIPS), after TIPS (approximately 6-8 weeks)

Number of Participants Diagnosed With Overt Hepatic Encephalopathy

Number of participants with episodes of overt hepatic encephalopathy (defined as West-Haven grade 2 or greater)

Time frame: Approximately 6-8 weeks

Number of Participants With Adverse Events

Adverse events in the PPI continuation versus discontinuation arms