Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF

Study Overview
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Brief Summary
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This study analyses the effect of intravenous branched chain amino acids (BCAA) on overt HE in patients with ACLF. The investigators plan to study the efficacy of combining intravenous BCAA with lactulose versus lactulose alone in the medical management of overt HE in patients with ACLF and its impact on overall survival and improvement in grade of HE.

Detailed Description
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Acute on chronic liver failure (ACLF) is a distinct clinical entity in the spectrum of chronic liver disease associated with high short term mortality. Hepatic encephalopathy (HE) is commonly seen in patients with ACLF and its treatment mainly involves non-absorbable disaccharides (lactulose/lactitol).Treatment of HE in ACLF is based on extrapolation of data available from cirrhotic patients. No studies have compared different treatment options for HE in patients with ACLF.

Official Title
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Efficacy of Lactulose Plus Intravenous Branched Chain Amino Acids Versus Lactulose Alone in Patients of Acute on Chronic Liver Failure With Overt Hepatic Encephalopathy: A Prospective Randomized Clinical Trial

Conditions
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Hepatic Encephalopathy, Acute-On-Chronic Liver Failure

Intervention / Treatment
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* Drug: Branched chain amino acid
* Drug: Lactulose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years Either gender Patients with ACLF (CANONIC definition) of any aetiology with HE ≥grade 2 as per West-Haven Criteria or Hepatic encephalopathy scoring algorithm (HESA) Exclusion Criteria: Those who do not consent to participate in the study Patients with structural brain lesions or stroke Inability to obtain informed consent from patient or relatives Severe preexisting cardiopulmonary disease Renal dysfunction (S. Creatinine ≥ 2mg/dL) Pregnancy/Lactation Post liver transplant patients HIV infection Patients who are on psychoactive drugs, like sedatives or antidepressants Patients who are too sick to carry out the protocol As the study was carried out during the peak of the COVID-19, patients who developed COVID-19 after randomization were excluded from the analysis as they were shifted to dedicated COVID-19 ICU's.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective interventional cohort study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV BCAA + Lactulose<br>IV Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose | Drug: Branched chain amino acid<br>* Intravenous branched chain amino acids will be given for 3 days to patients in experimental arm<br>Drug: Lactulose<br>* Oral lactulose will be given to patients in both arms<br>|
| Active Comparator: Lactulose alone<br>Oral Lactulose alone | Drug: Lactulose<br>* Oral lactulose will be given to patients in both arms<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement of Survival | All cause Mortality assessment | At day day 28 | 
| Improvement of encephalopathy by ≥ 1 grade | Improvement in hepatic encephalopathy | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in level of ammonia |  | 48 and 72 hours | 
| Reduction of consciousness recovery time among survivors |  | 30 days | 
| Prolongation of time to death among non-survivors |  | 30 days | 
| Prevention/reduction of cerebral edema based on optic nerve sheath diameter |  | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bispectral index, branched chain amino acids, hepatic encephalopathy, lactulose, acute on chronic liver failure