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

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

Interventions

DRUG

Oral Branched chain Amino acid

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

DRUG

Rifaximin 550 MG

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

DRUG

Lactulose

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

DRUG

Placebo for BCAA

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

DRUG

Placebo for Rifaximin 550mg

Identical placebo sugar pills will be used as a placebo.

Sponsors & Collaborators

• Indian Council of Medical Research

  collaborator OTHER_GOV

• Post Graduate Institute of Medical Education and Research, Chandigarh

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

65 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-02-01

Primary Completion

2026-08-31

Completion

2027-08-31

Countries

• India

Study Locations