Deprescribing Proton Pump Inhibitors to Reduce Post-TIPS Hepatic Encephalopathy

NCT05070351 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Pro00108517
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatic Encephalopathy

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (5)

• Change in Per-protocol Evaluation of Minimal Hepatic Encephalopathy

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

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

  Baseline (TIPS), after TIPS (approximately 6-8 weeks)

• Change in Gastroesophageal Reflux Specific Quality of Life

  Baseline (TIPS), after TIPS (approximately 6-8 weeks)

• Number of Participants Diagnosed With Overt Hepatic Encephalopathy

  Approximately 6-8 weeks

• Number of Participants With Adverse Events

  Approximately 6-8 weeks

Other Outcomes (2)

• Number of Participants With On-demand Requirement for Acid Suppression Therapy

  Approximately 6-8 weeks

• Change in Gastrointestinal Tract Microbiome

  Approximately 6-8 weeks

Study Arms (2)

PPI deprescribing arm

EXPERIMENTAL

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

Drug: PPI deprescribing

PPI continuation arm

NO INTERVENTION

Patients will be instructed to continue taking their PPI (at least 20 mg omeprazole equivalent daily) as usual.

Interventions

PPI deprescribing DRUG

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.

PPI deprescribing arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Hepatic Encephalopathy

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: James Ronald, MD PhD FSIR
• Organization: Duke University

james.ronald@duke.edu

919-684-7299

Study Officials

• James Ronald, MD PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: October 7, 2021
• Study Start: January 3, 2022
• Primary Completion: June 2, 2025
• Study Completion: June 2, 2025
• Last Updated: September 10, 2026
• Results First Posted: September 10, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)