Deprescribing Proton Pump Inhibitors to Reduce Post-TIPS Hepatic Encephalopathy

Phase 1

Recruiting

• Conditions: Hepatic Encephalopathy
• Interventions: Drug: PPI deprescribing

• Registration Number: NCT05070351
• Lead Sponsor: Duke University

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.

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2021-09-27
• Study First Submitted QC: 2021-09-27
• Study First Posted: 2021-10-07
• Study Start: 2022-01-03
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-06
• Primary Completion: 2028-10
• Study Completion: 2028-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PPI deprescribing arm	PPI deprescribing	Patients taking a PPI (at least 20 mg omeprazole equivalent daily) will be instructed to stop taking their PPI.

Primary Outcome Measures

Name	Time	Method
Minimal hepatic encephalopathy	Approximately 6-8 weeks	Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score

Secondary Outcome Measures

Name	Time	Method
Overt hepatic encephalopathy	Approximately 6-8 weeks	Episodes of overt hepatic encephalopathy (defined as West-Haven grade 2 or greater)
Per-protocol evaluation of minimal hepatic encephalopathy	Approximately 6-8 weeks	Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score, based on actual reported PPI use
Adverse events	Approximately 6-8 weeks	Adverse events in the PPI continuation versus discontinuation arms
Chronic liver disease specific quality of life	Approximately 6-8 weeks	Chronic liver disease (CLDQ) specific QOL assessment
Gastroesophageal reflux specific quality of life	Approximately 6-8 weeks	Gastroesophageal reflux (QOLRAD) specific QOL assessment
On-demand requirement for acid suppression therapy	Approximately 6-8 weeks	Proportion of patients in the PPI discontinuation arm needing on-demand H2 blockers or PPIs for gastroesophageal reflux symptoms

Trial Locations

Locations (1)

Duke University Hospital; 🇺🇸 Durham, North Carolina, United States