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

Primary Purpose

Hepatic Encephalopathy, Acute-On-Chronic Liver Failure

Status
Completed
Phase
Phase 1
Locations
India
Study Type
Interventional
Intervention
Branched chain amino acid
Lactulose
Sponsored by
Postgraduate Institute of Medical Education and Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatic Encephalopathy focused on measuring branched chain amino acids, hepatic encephalopathy, lactulose, acute on chronic liver failure, bispectral index

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • PGIMER

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

IV BCAA + Lactulose

Lactulose alone

Arm Description

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

Oral Lactulose alone

Outcomes

Primary Outcome Measures

Improvement of Survival
All cause Mortality assessment
Improvement of encephalopathy by ≥ 1 grade
Improvement in hepatic encephalopathy

Secondary Outcome Measures

Reduction in level of ammonia
Reduction of consciousness recovery time among survivors
Prolongation of time to death among non-survivors
Prevention/reduction of cerebral edema based on optic nerve sheath diameter

Full Information

First Posted
September 28, 2019
Last Updated
August 14, 2022
Sponsor
Postgraduate Institute of Medical Education and Research
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1. Study Identification

Unique Protocol Identification Number
NCT04238416
Brief Title
Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF
Acronym
BCAA-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

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
November 1, 2019 (Actual)
Primary Completion Date
December 30, 2021 (Actual)
Study Completion Date
December 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Postgraduate Institute of Medical Education and Research

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Encephalopathy, Acute-On-Chronic Liver Failure
Keywords
branched chain amino acids, hepatic encephalopathy, lactulose, acute on chronic liver failure, bispectral index

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Prospective interventional cohort study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
70 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IV BCAA + Lactulose
Arm Type
Experimental
Arm Description
IV Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose
Arm Title
Lactulose alone
Arm Type
Active Comparator
Arm Description
Oral Lactulose alone
Intervention Type
Drug
Intervention Name(s)
Branched chain amino acid
Intervention Description
Intravenous branched chain amino acids will be given for 3 days to patients in experimental arm
Intervention Type
Drug
Intervention Name(s)
Lactulose
Intervention Description
Oral lactulose will be given to patients in both arms
Primary Outcome Measure Information:
Title
Improvement of Survival
Description
All cause Mortality assessment
Time Frame
At day day 28
Title
Improvement of encephalopathy by ≥ 1 grade
Description
Improvement in hepatic encephalopathy
Time Frame
72 hours
Secondary Outcome Measure Information:
Title
Reduction in level of ammonia
Time Frame
48 and 72 hours
Title
Reduction of consciousness recovery time among survivors
Time Frame
30 days
Title
Prolongation of time to death among non-survivors
Time Frame
30 days
Title
Prevention/reduction of cerebral edema based on optic nerve sheath diameter
Time Frame
72 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Madhumita Premkumar, MD, DM
Organizational Affiliation
Postgraduate Institute of Medical Education and Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
PGIMER
City
Chandigarh
ZIP/Postal Code
160012
Country
India

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
21163546
Citation
Shawcross DL, Sharifi Y, Canavan JB, Yeoman AD, Abeles RD, Taylor NJ, Auzinger G, Bernal W, Wendon JA. Infection and systemic inflammation, not ammonia, are associated with Grade 3/4 hepatic encephalopathy, but not mortality in cirrhosis. J Hepatol. 2011 Apr;54(4):640-9. doi: 10.1016/j.jhep.2010.07.045. Epub 2010 Dec 1.
Results Reference
background
PubMed Identifier
9504517
Citation
Donovan JP, Schafer DF, Shaw BW Jr, Sorrell MF. Cerebral oedema and increased intracranial pressure in chronic liver disease. Lancet. 1998 Mar 7;351(9104):719-21. doi: 10.1016/S0140-6736(97)07373-X.
Results Reference
background
PubMed Identifier
17006913
Citation
Albrecht J, Norenberg MD. Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology. 2006 Oct;44(4):788-94. doi: 10.1002/hep.21357.
Results Reference
background
PubMed Identifier
31966
Citation
Norenberg MD, Martinez-Hernandez A. Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 1979 Feb 2;161(2):303-10. doi: 10.1016/0006-8993(79)90071-4.
Results Reference
background
PubMed Identifier
10733001
Citation
Albrecht J, Dolinska M, Hilgier W, Lipkowski AW, Nowacki J. Modulation of glutamine uptake and phosphate-activated glutaminase activity in rat brain mitochondria by amino acids and their synthetic analogues. Neurochem Int. 2000 Apr;36(4-5):341-7. doi: 10.1016/s0197-0186(99)00142-4.
Results Reference
background
PubMed Identifier
10336125
Citation
Laake JH, Takumi Y, Eidet J, Torgner IA, Roberg B, Kvamme E, Ottersen OP. Postembedding immunogold labelling reveals subcellular localization and pathway-specific enrichment of phosphate activated glutaminase in rat cerebellum. Neuroscience. 1999;88(4):1137-51. doi: 10.1016/s0306-4522(98)00298-x.
Results Reference
background
PubMed Identifier
24128414
Citation
Cordoba J, Ventura-Cots M, Simon-Talero M, Amoros A, Pavesi M, Vilstrup H, Angeli P, Domenicali M, Gines P, Bernardi M, Arroyo V; CANONIC Study Investigators of EASL-CLIF Consortium. Characteristics, risk factors, and mortality of cirrhotic patients hospitalized for hepatic encephalopathy with and without acute-on-chronic liver failure (ACLF). J Hepatol. 2014 Feb;60(2):275-81. doi: 10.1016/j.jhep.2013.10.004. Epub 2013 Oct 12.
Results Reference
background
PubMed Identifier
818729
Citation
Fischer JE, Rosen HM, Ebeid AM, James JH, Keane JM, Soeters PB. The effect of normalization of plasma amino acids on hepatic encephalopathy in man. Surgery. 1976 Jul;80(1):77-91.
Results Reference
result
PubMed Identifier
30568347
Citation
Dam G, Aamann L, Vistrup H, Gluud LL. The role of Branched Chain Amino Acids in the treatment of hepatic Encephalopathy. J Clin Exp Hepatol. 2018 Dec;8(4):448-451. doi: 10.1016/j.jceh.2018.06.004. Epub 2018 Jun 27.
Results Reference
result
PubMed Identifier
6749458
Citation
Rossi-Fanelli F, Riggio O, Cangiano C, Cascino A, De Conciliis D, Merli M, Stortoni M, Giunchi G. Branched-chain amino acids vs lactulose in the treatment of hepatic coma: a controlled study. Dig Dis Sci. 1982 Oct;27(10):929-35. doi: 10.1007/BF01316578.
Results Reference
result
PubMed Identifier
25715177
Citation
Gluud LL, Dam G, Les I, Cordoba J, Marchesini G, Borre M, Aagaard NK, Vilstrup H. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2015 Feb 25;(2):CD001939. doi: 10.1002/14651858.CD001939.pub2.
Results Reference
result

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Intravenous Branched Chain Amino Acids for Hepatic Encephalopathy in ACLF

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