Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF

Phase 1

Completed

• Conditions: Hepatic Encephalopathy; Acute-On-Chronic Liver Failure
• Interventions: Drug: Branched chain amino acid; Drug: Lactulose

• Registration Number: NCT04238416
• Lead Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh

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.

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 Timeline

• Study First Submitted: 2019-09-28
• Study Start: 2019-11-01
• Study First Submitted QC: 2020-01-22
• Study First Posted: 2020-01-23
• Primary Completion: 2021-12-30
• Study Completion: 2021-12-30
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-14
• Last Update Posted: 2022-08-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

1. Age 18-75 years
2. Either gender
3. 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

1. Those who do not consent to participate in the study
2. Patients with structural brain lesions or stroke
3. Inability to obtain informed consent from patient or relatives
4. Severe preexisting cardiopulmonary disease
5. Renal dysfunction (S. Creatinine ≥ 2mg/dL)
6. Pregnancy/Lactation
7. Post liver transplant patients
8. HIV infection
9. Patients who are on psychoactive drugs, like sedatives or antidepressants
10. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IV BCAA + Lactulose	Branched chain amino acid	IV Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose
IV BCAA + Lactulose	Lactulose	IV Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose
Lactulose alone	Lactulose	Oral Lactulose alone

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (1)

PGIMER; 🇮🇳 Chandigarh, India