Clinical trial NCT05070351: Deprescribing Proton Pump Inhibitors to Reduce Post-TIPS Hepatic Encephalopathy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hepatic Encephalopathy
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2021-10-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Minimal hepatic encephalopathy
timeFrame: Approximately 6-8 weeks
Secondary outcomes:
measure: Per-protocol evaluation of minimal hepatic encephalopathy
timeFrame: Approximately 6-8 weeks
measure: Chronic liver disease specific quality of life
timeFrame: Approximately 6-8 weeks
measure: Gastroesophageal reflux specific quality of life
timeFrame: Approximately 6-8 weeks
measure: Overt hepatic encephalopathy
timeFrame: Approximately 6-8 weeks
measure: On-demand requirement for acid suppression therapy
timeFrame: Approximately 6-8 weeks
measure: Adverse events
timeFrame: Approximately 6-8 weeks
Other outcomes:
measure: Change in gastrointestinal tract microbiome
timeFrame: Approximately 6-8 weeks
Locations:
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
Study officials:
affiliation: Duke University
name: James Ronald, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: