Clinical trial NCT04238416: Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Encephalopathy
Acute-On-Chronic Liver Failure
Keywords: branched chain amino acids
hepatic encephalopathy
lactulose
acute on chronic liver failure
bispectral index
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2020-01-23
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective interventional cohort study
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Improvement of Survival
timeFrame: At day day 28
measure: Improvement of encephalopathy by ≥ 1 grade
timeFrame: 72 hours
Secondary outcomes:
measure: Reduction in level of ammonia
timeFrame: 48 and 72 hours
measure: Reduction of consciousness recovery time among survivors
timeFrame: 30 days
measure: Prolongation of time to death among non-survivors
timeFrame: 30 days
measure: Prevention/reduction of cerebral edema based on optic nerve sheath diameter
timeFrame: 72 hours
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: PGIMER
Study officials:
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Madhumita Premkumar, MD, DM
role: PRINCIPAL_INVESTIGATOR
References:
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