BCAA vs. Rifaximin in Patients With Cirrhosis for Secondary Prophylaxis of HE

NCT06538077 | Recruiting Phase 4 DMC

• 1 other identifier: PGI/HEP/567
• Study Type: interventional
• Target: 336
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale

• Patients who recover from an episode of overt HE(OHE) are at risk of recurrent episodes of HE and persistent minimal hepatic encephalopathy, impacting their daily functioning and mental health.
• A multicentric pan-India team will evaluate the role of oral branched-chain amino acids (BCAA) vs Rifaximin as secondary prophylaxis following overt HE as compared with improvement in cognitive function. Novelty:
• This study is intended to investigate the role of BCAA vs rifaximin as the ideal second-line therapy for HE management, recurrence, and overall health, including cognitive function, depression and anxiety.
• The head-to-head comparison of BCAA+lactulose+ pill-placebo vs rifaximin+ lactulose+ powder-placebo ensures minimization of bias and has adequate power to determine rates of recurrence, Objectives:
• To assess the 1st breakthrough episode of HE during 6months in BCAA vs rifaximin groups as ideal secondary prophylaxis in HE. Methodology
• Double-blind placebo-controlled double-dummy randomized trial of BCAA supplementation vs rifaximin as the ideal second-line therapy in patients with cirrhosis who have recovered from an episode of OHE. Expected Outcome
• Ideal second line agent HE prophylaxis (rifaximin or BCAA) following 1st line lactulose is unclear in an Indian context where dysbiosis and sarcopenia are prevalent, and cost of therapy needs to be optimized.
• Optimal HE management prevents recurrence episodes of HE, and improves prognosis, neurocognitive function, and overall health-related quality of life(HRQOL).
• Creation of a management algorithm based deductive models incorporating etiology and severity of liver disease, cognitive performance, sarcopenia, and ammonia, and neuropsychiatric impact of using BCAA vs Rifaximin will be created.

Conditions

Hepatic Encephalopathy; Decompensated Cirrhosis; Minimal Hepatic Encephalopathy

Keywords

Hepatic encephalopathy; Branched-chain amino acids; Computerized neurocognitive test battery; Double blind placebo controlled multicentric randomized controlled trial; rifaximin

Outcome Measures

Primary Outcomes (1)

• Number of breakthrough event of overt hepatic encephalopathy in BCAA vs rifaximin arm

  Time to a breakthrough overt HE episode will be the duration (number of days) from time of first dose of study drug to the first breakthrough overt HE episode. The number of events of a first breakthrough overt HE episode during the treatment period will be assessed

  24 Weeks

Secondary Outcomes (17)

• Computerized Cognitive Test battery for Cognitive performance

  At Enrolment

• Computerized Cognitive Test battery for Cognitive performance

  30 days

• Computerized Cognitive Test battery for Cognitive performance

  90 days

• Psychiatric Assessment

  0 days

• Psychiatric Assessment

  0 days

Study Arms (2)

A1=Experimental:

EXPERIMENTAL

Drug: Oral BCAA + Rifaximin placebo + Lactulose ( Oral BCAA 15 gm in once daily dose With Lactulose for 12 weeks)

Drug: Oral Branched chain Amino acid; Drug: Lactulose; Drug: Placebo for Rifaximin 550mg

A2= Experimental:

EXPERIMENTAL

Drug: Rifaximin+ BCAA Placebo + Lactulose ( Oral Rifaximin 550 mg twice daily daily + Lactulose therapy for 12 weeks)

Drug: Rifaximin 550 MG; Drug: Lactulose; Drug: Placebo for BCAA

Interventions

Oral Branched chain Amino acid DRUG

The active drug BCAA supplement will be dispensed in a dose of 15 gm once daily x 12 weeks

A1=Experimental:

Rifaximin 550 MG DRUG

Active drug rifaximin will be dispensed in a dose of 550mg twice daily x 12 weeks

A2= Experimental:

Lactulose DRUG

Both groups will be treated with will be treated with 30-60 ml lactulose three times a day to ensure passage of 2-3 semisoft stools per day

A1=Experimental:; A2= Experimental:

Placebo for BCAA DRUG

A placebo comparator of 15 gm of skimmed milk powder will be used.

A2= Experimental:

Placebo for Rifaximin 550mg DRUG

Identical placebo sugar pills will be used as a placebo.

A1=Experimental:

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Any gender
• Discharged from the hospital following an episode of overt hepatic encephalopathy.
• Participants able to give informed consent

You may not qualify if:

• Subjects with active bacterial or fungal infection
• Subjects with active or very recent gastrointestinal bleeding in the last 2 weeks.
• Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy according to the West-Haven classification.
• Conditions that can impact interpretation of cognitive function:
• i) Untreated viremic hepatitis C virus infection ii) Established neurological/degenerative disorders iii) Patient undergoing active alcohol withdrawal treatment Iv) Patient is intoxicated or under the influence of illicit drugs as per clinician assessment V) Treatment with antipsychotics or other psychotropic drugs with sedative effects
• Patients with active hepatocellular carcinoma or history of hepatocellular carcinoma that is in remission for less than six months.
• Patients with a history of significant extrahepatic disease with impaired short-term prognosis, including: i) Congestive heart failure New York Heart Association Grade III/IV or ejection fraction\<30% ii) COPD: GOLD \>2, ii) Chronic kidney disease with serum creatinine \>2mg/dL or under renal replacement therapy.
• Patients with current extra hepatic malignancies, including solid tumours and hematologic disorders.
• Patients with MELD\>20
• Patients with mental incapacity, or those unlikely to survive 12 weeks or any other reason considered by the investigator precluding adequate understanding, cooperation, or compliance in the study activities.
• Patients with TIPS shunt in situ
• Refusal or inability to give informed consent

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead
• Indian Council of Medical Research: collaborator

Study Sites (1)

PGIMER

Chandigarh, India

RECRUITING

MeSH Terms

Conditions

Hepatic Encephalopathy

Interventions

Amino Acids, Branched-Chain; Rifaximin; Lactulose

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Amino Acids; Amino Acids, Peptides, and Proteins; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Central Study Contacts

Madhumita Premkumar

CONTACT

+9101722754777; drmadhumitap@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind double dummy placebo-controlled multicentric randomized controlled trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ASSOCIATE PROFESSOR

Model Details: In addition to the BCAA vs Rifaximin, both groups will be treated with 30-60 ml lactulose three times a day to ensure passage of 2-3 semisoft stools per day.

Study Record Dates

• First Submitted: April 23, 2024
• First Posted: August 5, 2024
• Study Start: February 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)