BCAA-ACLF: Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF

Sponsor

Postgraduate Institute of Medical Education and Research (Other)

Overall Status

Completed

CT.gov ID

NCT04238416

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

2.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatic Encephalopathy Acute-On-Chronic Liver Failure	Drug: Branched chain amino acid Drug: Lactulose	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective interventional cohort studyProspective interventional cohort study

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 1, 2019

Actual Primary Completion Date :

Dec 30, 2021

Actual Study Completion Date :

Dec 30, 2021

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: IV BCAA + Lactulose

IV Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose

Drug: Branched chain amino acid

Intravenous branched chain amino acids will be given for 3 days to patients in experimental arm

Drug: Lactulose

Oral lactulose will be given to patients in both arms

Active Comparator: Lactulose alone

Oral Lactulose alone

Drug: Lactulose

Oral lactulose will be given to patients in both arms

Outcome Measures

Primary Outcome Measures

Improvement of Survival [At day day 28]
All cause Mortality assessment
Improvement of encephalopathy by ≥ 1 grade [72 hours]
Improvement in hepatic encephalopathy

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.