Deprescribing Proton Pump Inhibitors to Reduce Post-TIPS Hepatic Encephalopathy

Hepatic Encephalopathy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05070351
• Other study ID #: Pro00108517
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 3, 2022
• Est. completion date: October 2028

Study information

• Verified date: March 2024
• Source: Duke University
• Contact: James Ronald, MD PhD
• Phone: 919-684-7299
• Email: james.ronald[@]duke.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: October 2028
• Est. primary completion date: October 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Hepatic Encephalopathy

Intervention

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.

Locations

Country	Name	City	State
United States	Duke University Hospital	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Duke University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	Minimal hepatic encephalopathy	Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score	Approximately 6-8 weeks
Secondary	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
Secondary	Chronic liver disease specific quality of life	Chronic liver disease (CLDQ) specific QOL assessment	Approximately 6-8 weeks
Secondary	Gastroesophageal reflux specific quality of life	Gastroesophageal reflux (QOLRAD) specific QOL assessment	Approximately 6-8 weeks
Secondary	Overt hepatic encephalopathy	Episodes of overt hepatic encephalopathy (defined as West-Haven grade 2 or greater)	Approximately 6-8 weeks
Secondary	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
Secondary	Adverse events	Adverse events in the PPI continuation versus discontinuation arms	Approximately 6-8 weeks