Deprescribing Proton Pump Inhibitors to Reduce Post-TIPS Hepatic Encephalopathy

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

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 Overview

• Status: Recruiting
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Drug: PPI deprescribing

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: James Ronald, MD PhD; Phone Number: 919-684-7299; Email: james.ronald@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Hospital
      • Contact: Clinical Research Coordinator; Phone Number: 919-684-7810; Email: latonia.strader@duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in gastrointestinal tract microbiome	Pre-TIPS to post-TIPS change in stool taxon abundances as measured by 16S rRNA sequencing	Approximately 6-8 weeks

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: James Ronald, MD PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2022
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2028

Study Registration Dates

• First Submitted: September 27, 2021
• First Submitted That Met QC Criteria: September 27, 2021
• First Posted (Actual): October 7, 2021

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: Pro00108517

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No