Cirrhosis, Hepatic Encephalopathy, Portosystemic Encephalopathy, PSE
Conditions
Keywords
Hepatic Encephalopathy, HE, Cirrhosis, PSE, Portosystemic Encephalopathy, Hepatic coma, AMS, Altered mental status, Complications of cirrhosis, Chronic liver disease
Brief summary
This study is being done to find out if the laxative polyethylene glycol (also known as GoLYTELY® or Miralax®) can treat your hepatic encephalopathy (confusion due to your liver disease and/or cirrhosis) better and/or more safely than lactulose (another laxative). In this study, the investigators will evaluate if polyethylene glycol (GoLYTELY®) is more effective than lactulose on neurocognition (memory and thinking skills) and determine if it decreases the hospital stay.
Interventions
DRUGPolyethylene glycol 3350-electrolyte solution (GoLYTELY®)
If randomized to this arm, subjects will receive a 1 time dose of 1 gallon
DRUGLactulose
If randomized to this arm, subjects will receive 10-30 grams per standard of care
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 18-80 2. Male and female subjects of all races and ethnicities including Spanish speaking subjects 3. Cirrhosis of any cause 4. Any grade of hepatic encephalopathy (1-4) 5. A legally authorized representative has to be able and willing to comply with all protocol procedures and to understand, sign and date an informed consent document, and authorize access to protected health information on the subjects behalf
Exclusion criteria
1. Acute liver failure 2. Structural brain lesions (as indicated by computed tomography imaging if available and confirmed by neurological exam) 3. Other causes of altered mental status (i.e. not meeting the definition of hepatic encephalopathy) 4. Previous use of rifaximin or neomycin in past 7 days 5. Prisoners 6. Pregnancy 7. \<18 years old 8. Serum sodium \<125 mEq/L 9. Receiving \> 1 dose of lactulose prior to enrollment 10. Uncontrolled infection with hemodynamic instability requiring vasopressors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With an Improvement of 1 or More in HE Grade at 24 Hours | Baseline to 24 hours | Hepatic Encephalopathy Scoring Algorithm (HESA) at the 24 hour time point of when the subject was recruited (HESA improvement by at least 1 grade). HESA ranges from 0 to 3, with higher numbers indicating a more severe grade of hepatic encephalopathy. Study will continue at every 24 hour time point until the subject achieves his or her baseline mental state and/or grade 0 based on the HESA |
| Change in HE Grade at 24 Hours | Baseline to 24 hours | Hepatic Encephalopathy Scoring Algorithm (HESA) at the 24 hour time point of when the subject was recruited. HESA ranges from 0 to 3, with higher numbers indicating a more severe grade of hepatic encephalopathy. Study will continue at every 24 hour time point until the subject achieves his or her baseline mental state and/or grade 0 based on the HESA |
Secondary
| Measure | Time frame |
|---|---|
| Hospital Duration/Length of Stay | From time of admission to time of discharge or death |
Countries
United States
Participant flow
Recruitment details
This randomized clinical trial was performed at Parkland Memorial Hospital, Dallas, Texas, from January 2011 to June 2012. All patients presenting to the emergency department with known cirrhosis and altered mental status (AMS) were eligible.
Pre-assignment details
A total of 186 patients were screened; 50 eligible patients were randomized to standard-of-care treatment (lactulose) or PEG. The most common reasons for exclusion were that the patient had received more than 1 dose of lactulose in the emergency department prior to consent, that a LAR was not available, or that the patient did not have HE.
Participants by arm
| Arm | Count |
|---|---|
| Polyethylene Glycol 3350-electrolyte Solution (GoLYTELY®) Polyethylene glycol 3350-electrolyte solution (GoLYTELY®): If randomized to this arm, subjects will receive a 1 time dose of 1 gallon | 25 |
| Lactulose Per standard of care
Lactulose: If randomized to this arm, subjects will receive 10-30 grams per standard of care | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discharged prior to 24 hr assessment | 1 | 0 |
| Overall Study | Refused HESA | 1 | 0 |
Baseline characteristics
| Characteristic | Lactulose | Polyethylene Glycol 3350-electrolyte Solution (GoLYTELY®) | Total |
|---|---|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 11 | 56 years STANDARD_DEVIATION 7 | 56 years STANDARD_DEVIATION 9 |
| Albumin | 2.8 g/dL STANDARD_DEVIATION 0.5 | 2.7 g/dL STANDARD_DEVIATION 0.6 | 2.7 g/dL STANDARD_DEVIATION 0.6 |
| Blood Lab Values Blood Urea Nitrogen | 21 mg/dL STANDARD_DEVIATION 11 | 30 mg/dL STANDARD_DEVIATION 17 | 26 mg/dL STANDARD_DEVIATION 15 |
| Blood Lab Values Creatinine | 1.12 mg/dL STANDARD_DEVIATION 0.52 | 1.7 mg/dL STANDARD_DEVIATION 1.29 | 1.41 mg/dL STANDARD_DEVIATION 1.02 |
| Blood Lab Values Total Bilirubin | 2.9 mg/dL STANDARD_DEVIATION 1.4 | 3.6 mg/dL STANDARD_DEVIATION 3 | 3.3 mg/dL STANDARD_DEVIATION 2.3 |
| Cirrhosis cause Alcoholic Liver Disease | 9 participants | 10 participants | 19 participants |
| Cirrhosis cause Cryptogenic | 6 participants | 6 participants | 12 participants |
| Cirrhosis cause Hepatitis B | 1 participants | 1 participants | 2 participants |
| Cirrhosis cause Hepatitis C | 9 participants | 8 participants | 17 participants |
| International Normalized Ratio (INR) | 1.4 unitless (ratio) STANDARD_DEVIATION 0.3 | 1.5 unitless (ratio) STANDARD_DEVIATION 0.4 | 1.5 unitless (ratio) STANDARD_DEVIATION 0.4 |
| MELD and CTP Scores CTP score | 10 units on a scale STANDARD_DEVIATION 1 | 10 units on a scale STANDARD_DEVIATION 2 | 10 units on a scale STANDARD_DEVIATION 2 |
| MELD and CTP Scores MELD score | 17 units on a scale STANDARD_DEVIATION 5 | 17 units on a scale STANDARD_DEVIATION 6 | 17 units on a scale STANDARD_DEVIATION 5 |
| Race/Ethnicity, Customized African American | 2 participants | 2 participants | 4 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White, Hispanic | 15 participants | 20 participants | 35 participants |
| Race/Ethnicity, Customized White, non-Hispanic | 8 participants | 2 participants | 10 participants |
| Region of Enrollment United States | 25 participants | 25 participants | 50 participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 15 Participants | 16 Participants | 31 Participants |
| White Blood Cell count | 6.2 cells*10^9/L STANDARD_DEVIATION 2.6 | 6.3 cells*10^9/L STANDARD_DEVIATION 2.6 | 6.2 cells*10^9/L STANDARD_DEVIATION 2.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 25 |
| serious Total, serious adverse events | 3 / 25 | 5 / 25 |
Outcome results
Primary
Change in HE Grade at 24 Hours
Hepatic Encephalopathy Scoring Algorithm (HESA) at the 24 hour time point of when the subject was recruited. HESA ranges from 0 to 3, with higher numbers indicating a more severe grade of hepatic encephalopathy. Study will continue at every 24 hour time point until the subject achieves his or her baseline mental state and/or grade 0 based on the HESA
Time frame: Baseline to 24 hours
Population: All participants who completed the study
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Polyethylene Glycol 3350-electrolyte Solution (GoLYTELY®) | Change in HE Grade at 24 Hours | No HESA improvement | 2 participants |
| Polyethylene Glycol 3350-electrolyte Solution (GoLYTELY®) | Change in HE Grade at 24 Hours | improvement of 1 HESA grade | 10 participants |
| Polyethylene Glycol 3350-electrolyte Solution (GoLYTELY®) | Change in HE Grade at 24 Hours | improvement of 2 HESA grades | 9 participants |
| Polyethylene Glycol 3350-electrolyte Solution (GoLYTELY®) | Change in HE Grade at 24 Hours | improvement of 3 HESA grades | 1 participants |
| Polyethylene Glycol 3350-electrolyte Solution (GoLYTELY®) | Change in HE Grade at 24 Hours | HESA grade 0 at 24 hours | 10 participants |
| Lactulose | Change in HE Grade at 24 Hours | HESA grade 0 at 24 hours | 2 participants |
| Lactulose | Change in HE Grade at 24 Hours | improvement of 3 HESA grades | 1 participants |
| Lactulose | Change in HE Grade at 24 Hours | improvement of 1 HESA grade | 9 participants |
| Lactulose | Change in HE Grade at 24 Hours | No HESA improvement | 12 participants |
| Lactulose | Change in HE Grade at 24 Hours | improvement of 2 HESA grades | 3 participants |
Primary
Number of Participants With an Improvement of 1 or More in HE Grade at 24 Hours
Hepatic Encephalopathy Scoring Algorithm (HESA) at the 24 hour time point of when the subject was recruited (HESA improvement by at least 1 grade). HESA ranges from 0 to 3, with higher numbers indicating a more severe grade of hepatic encephalopathy. Study will continue at every 24 hour time point until the subject achieves his or her baseline mental state and/or grade 0 based on the HESA
Time frame: Baseline to 24 hours
Population: All participants who completed the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Polyethylene Glycol 3350-electrolyte Solution (GoLYTELY®) | Number of Participants With an Improvement of 1 or More in HE Grade at 24 Hours | 21 participants |
| Lactulose | Number of Participants With an Improvement of 1 or More in HE Grade at 24 Hours | 13 participants |
Secondary
Hospital Duration/Length of Stay
Time frame: From time of admission to time of discharge or death
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Polyethylene Glycol 3350-electrolyte Solution (GoLYTELY®) | Hospital Duration/Length of Stay | 4 days | Standard Deviation 3 |
| Lactulose | Hospital Duration/Length of Stay | 8 days | Standard Deviation 12 |