A Retrospective, Open-label, Uncontrolled Cohort Study to Assess the Effectiveness and Safety of Lactulose Retention Enema in the Treatment of Cirrhotic Patients With Grade 3 or 4 (West Haven Criteria) Hepatic Encephalopathy (HE) [The RETRO Study]

Study Overview
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Brief Summary
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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
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Data to be collected: Data that would be collected for the study as part of retrospective chart review: Patient demographics: age, gender, weight Medical history Etiology of cirrhosis (alcohol abuse, hepatitis, autoimmune, cryptogenic, other) Diagnosis of cirrhosis History of previous HE (if yes, the number of episodes in the past) Grade of HE (as per the West-Haven criteria) at admission, 24 hrs and 48 hours post treatment with lactulose Precipitating factor(s) of HE (Dehydration, GI bleeding, protein overload, constipation, infection, others) Dose and duration of lactulose enema Treatment given for precipitating factors Laboratory data on haemoglobin, platelet, bilirubin, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, creatinine, sodium, potassium, and blood ammonia Complete reversal of deep-grade HE (< Grade 2 as per West-Haven criteria) (yes/no) Time to complete reversal of deep-grade HE Number of days in hospital Adverse drug reaction experienced by the patient Complications experienced by the patient Other pharmacovigilance relevant information (OPRI)

Official Title
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A Retrospective, Open-label, Uncontrolled Cohort Study to Assess the Effectiveness and Safety of Lactulose Retention Enema in the Treatment of Cirrhotic Patients With Grade 3 or 4 (West Haven Criteria) Hepatic Encephalopathy (HE) [The RETRO Study]

Conditions
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Hepatic Encephalopathy

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with cirrhosis (grade 3 & 4 per west haven cr.)<br>Patients with cirrhosis having grade 3 or grade 4 (West Haven Criteria) hepatic encephalopathy who were treated with Lactulose retention enema | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 24 hrs | 
| 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 | 48 hrs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | HE Grade shift at 24 hrs and HE Grade shift at 48 hrs | 
| 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 | up to 48 hrs | 
| Mortality | Mortality in patients treated with lactulose retention enema | within 48 hrs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lactulose Retention Enema, Hepatic Encephalopathy, Grade 3 or 4 West Haven Criteria, The Retro Study