Hepatic Encephalopathy
Conditions
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.
Interventions
DRUGPPI 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.
Sponsors
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Minimal Hepatic Encephalopathy | Baseline (before transjugular intrahepatic portosystemic shunt - TIPS), after TIPS (approximately 6-8 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Per-protocol Evaluation of Minimal Hepatic Encephalopathy | Baseline (before TIPS), after TIPS (approximately 6-8 weeks) | Minimal hepatic encephalopathy, as assessed by psychometric hepatic encephalopathy score, based on actual reported PPI (Proton Pump Inhibitors) use. 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. |
| Change in Chronic Liver Disease Specific Quality of Life (CLDQ) | Baseline (TIPS), after TIPS (approximately 6-8 weeks) | Chronic liver disease (CLDQ) specific QOL assessment. Reported as the score difference after TIPS compared to baseline (possible range -174 to +174). Higher numbers indicate worse quality of life. |
| Change in Gastroesophageal Reflux Specific Quality of Life | Baseline (TIPS), after TIPS (approximately 6-8 weeks) | Gastroesophageal reflux (QOLRAD) specific QOL assessment. Reported as the score difference after TIPS compared to baseline (possible range -150 to +150). Higher numbers indicate worse quality of life. |
| Number of Participants Diagnosed With Overt Hepatic Encephalopathy | Approximately 6-8 weeks | Number of participants with episodes of overt hepatic encephalopathy (defined as West-Haven grade 2 or greater) |
| Number of Participants With Adverse Events | Approximately 6-8 weeks | Adverse events in the PPI continuation versus discontinuation arms |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJames Ronald, MD PhD
Duke University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 9.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Region of Enrollment United States | 33 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 16 |
| other Total, other adverse events | 0 / 17 | 0 / 16 |
| serious Total, serious adverse events | 3 / 17 | 5 / 16 |
Outcome results
None listed