Hepatic Encephalopathy
Conditions
Keywords
Lactulose Retention Enema, Hepatic Encephalopathy, Grade 3 or 4 West Haven Criteria, The Retro Study
Brief summary
This is a retrospective study in adult patients with cirrhosis and grade 3 or 4 HE (West Haven Criteria) to evaluate the effectiveness and safety of lactulose retention enema in the treatment of deep grade HE (West Haven Criteria). The study will be conducted retrospectively in a multi center of a multispecialty tertiary care hospital in India, in which lactulose retention enema is the mainstay of management of cirrhotic patients with grade 3 or 4 HE (West Haven criteria). Dosing of lactulose retention enema in this study will be done according to the dosing described for rectal administration of lactulose (India): 300ml of lactulose mixed with 700ml of potable water to be used as a retention enema; the enema is to be retained for 30-60 minutes and repeated every 4-6 hours until the patient is able to take oral medication. This treatment regime is also the standard protocol of management of deep grade HE (West Haven criteria) in the study centers. The standard treatment protocol of deep grade HE (West Haven criteria) of the study centers will also ensure that all known contraindications of lactulose will be respected before administration of lactulose retention enema to the study patients. The retrospective hospital records of the patient population of interest within the past 6 months will be identified, and these records will be used to collect data required for analysis.
Detailed description
Data to be collected: Data that would be collected for the study as part of retrospective chart review: 1. Patient demographics: age, gender, weight 2. Medical history 3. Etiology of cirrhosis (alcohol abuse, hepatitis, autoimmune, cryptogenic, other) 4. Diagnosis of cirrhosis 5. History of previous HE (if yes, the number of episodes in the past) 6. Grade of HE (as per the West-Haven criteria) at admission, 24 hrs and 48 hours post treatment with lactulose 7. Precipitating factor(s) of HE (Dehydration, GI bleeding, protein overload, constipation, infection, others) 8. Dose and duration of lactulose enema 9. Treatment given for precipitating factors 10. Laboratory data on haemoglobin, platelet, bilirubin, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, sodium, potassium, and blood ammonia 11. Complete reversal of deep-grade HE (\< Grade 2 as per West-Haven criteria) (yes/no) 12. Time to complete reversal of deep-grade HE 13. Number of days in hospital 14. Adverse drug reaction experienced by the patient 15. Complications experienced by the patient 16. Other pharmacovigilance relevant information (OPRI)
Interventions
None listed
Sponsors
Abbott
Study design
Observational model
OTHER
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged between 18 and 65 years of either gender. * Patients admitted to the hospital with liver cirrhosis and grade 3 or grade 4 (West Haven Criteria) HE * Patients treated with lactulose retention enema within 48 hours of onset of grade 3 or 4 (West Haven Criteria) HE
Exclusion criteria
* Patients treated with agents other than lactulose retention enema for grade 3 or 4 (West Haven Criteria) HE. * Patients who had significant concomitant diseases that could impair or contribute to the impairment of consciousness * Patients who had a major neuropsychiatric illness * Patients who had a contraindication to lactulose, including Hypersensitivity to the active substance or to any of the ingredients; Galactosaemia; Gastrointestinal obstruction, digestive perforation or risk of digestive perforation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Reversal | 24 hrs | Percentage of patients with complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) Hepatic Encephalopathy after administration of lactulose retention enema |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Encephalopathy (HE) Grade Shift at 24 and 48 Hours | HE Grade shift at 24 hrs and HE Grade shift at 48 hrs | Grade shift at 24 and 48 hours - from baseline to 24 and 48 hours post administration of lactulose retention enema. Complete reversal of deep grade HE is defined as subjects having HE grade=\<grade 2 as per West-Haven criteria where grade 0 is Normal, Grade 1 is Mild lack of awareness, Grade 2 is Lethargic, Grade 3 is Somnolent but arousable and Grade 4 is Coma |
| Time to Complete Reversal | up to 48 hrs | Time to complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) HE after administration of lactulose retention enema |
| Mortality | within 48 hrs | Mortality in patients treated with lactulose retention enema |
Other
| Measure | Time frame | Description |
|---|---|---|
| Reduction in Blood Ammonia Level | reported at 48 hrs | Change from baseline was calculated at the end of treatment by using following formula wherever applicable: Change from baseline = Blood ammonia level at the end of treatment - Blood ammonia level at baseline |
| Duration of Hospital Stay | upto 30 days of hospital admission | — |
| Safety of Lactulose Retention Enema (Number of Adverse Drug Reactions & Complications). | Chart Review of Events over 48 Hour Period | Safety of Lactulose retention enema (number of adverse drug reactions & complications). Complications pertinent to lactulose retention enema are in reference to potential adverse effects associated with the use of rectal device associated with the application of the lactulose retention enema kit. |
Countries
India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema | 50 |
| Total | 50 |
Baseline characteristics
| Characteristic | Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants |
| Age, Continuous | 48.38 years STANDARD_DEVIATION 10.18 |
| Region of Enrollment India | 50 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 50 |
| other Total, other adverse events | 3 / 50 |
| serious Total, serious adverse events | 0 / 50 |
Outcome results
Primary
Complete Reversal
Percentage of patients with complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) Hepatic Encephalopathy after administration of lactulose retention enema
Time frame: 24 hrs
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Complete Reversal | 80 percentage of participants |
Primary
Complete Reversal
Percentage of patients with complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) Hepatic Encephalopathy after administration of lactulose retention enema
Time frame: 48 hrs
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Complete Reversal | 90 percentage of participants |
Secondary
Hepatic Encephalopathy (HE) Grade Shift at 24 and 48 Hours
Grade shift at 24 and 48 hours - from baseline to 24 and 48 hours post administration of lactulose retention enema. Complete reversal of deep grade HE is defined as subjects having HE grade=\<grade 2 as per West-Haven criteria where grade 0 is Normal, Grade 1 is Mild lack of awareness, Grade 2 is Lethargic, Grade 3 is Somnolent but arousable and Grade 4 is Coma
Time frame: HE Grade shift at 24 hrs and HE Grade shift at 48 hrs
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Hepatic Encephalopathy (HE) Grade Shift at 24 and 48 Hours | shift from HE Grade 4 to <2 after 24 hours | 20.0 percentage of participants |
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Hepatic Encephalopathy (HE) Grade Shift at 24 and 48 Hours | shift from HE Grade 3 to <2 after 48 hours | 95.56 percentage of participants |
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Hepatic Encephalopathy (HE) Grade Shift at 24 and 48 Hours | shift from HE Grade 4 to <2 after 48 hours | 40.0 percentage of participants |
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Hepatic Encephalopathy (HE) Grade Shift at 24 and 48 Hours | shift from HE Grade 3 to <2 after 24 hours | 86.67 percentage of participants |
Secondary
Mortality
Mortality in patients treated with lactulose retention enema
Time frame: within 48 hrs
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Mortality | 0 Participants |
Secondary
Time to Complete Reversal
Time to complete reversal of deep-grade (Grade 3 and 4 West-Haven Criteria) HE after administration of lactulose retention enema
Time frame: up to 48 hrs
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Time to Complete Reversal | 25.39 Hours | Standard Deviation 8.85 |
Other Pre-specified
Duration of Hospital Stay
Time frame: upto 30 days of hospital admission
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Duration of Hospital Stay | 229.4 hours | Standard Deviation 147.64 |
Other Pre-specified
Reduction in Blood Ammonia Level
Change from baseline was calculated at the end of treatment by using following formula wherever applicable: Change from baseline = Blood ammonia level at the end of treatment - Blood ammonia level at baseline
Time frame: reported at 48 hrs
Population: The ammonia levels were available at baseline for 28 patients where as the last observed blood ammonia level after administration of lactulose enema was available for 4 patients. Thus the change from baseline was calculated for 4 patients. The Change value = Visit value - Baseline Value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Reduction in Blood Ammonia Level | -70.6 Mcg/DL | Standard Deviation 11.32 |
Other Pre-specified
Safety of Lactulose Retention Enema (Number of Adverse Drug Reactions & Complications).
Safety of Lactulose retention enema (number of adverse drug reactions & complications). Complications pertinent to lactulose retention enema are in reference to potential adverse effects associated with the use of rectal device associated with the application of the lactulose retention enema kit.
Time frame: Chart Review of Events over 48 Hour Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients With Cirrhosis (Grade 3 & 4 Per West Haven cr.) | Safety of Lactulose Retention Enema (Number of Adverse Drug Reactions & Complications). | 5 number of events |