BCAA vs. Rifaximin in Patients With Cirrhosis for Secondary Prophylaxis of HE
Trial Parameters
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.
Eligibility Criteria
Inclusion Criteria: 1. Cirrhosis defined by standard clinical, ultrasonographic findings and/or histological criteria. Cirrhosis of any etiology may be included. However, patients with cirrhosis due to autoimmune hepatitis must be on stable corticosteroid doses for ≥3-month period before study inclusion; those with viral hepatitis, must similarly be on anti-viral therapy with controlled viremia or with SVR. 2. Any gender 3. Discharged from the hospital following an episode of overt hepatic encephalopathy. 4. Participants able to give informed consent Exclusion Criteria: 1. Subjects with active bacterial or fungal infection 2. Subjects with active or very recent gastrointestinal bleeding in the last 2 weeks. 3. Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy according to the West-Haven classification. 4. Conditions that can impact interpretation of cognitive function: i) Untreated viremic hepatitis C virus infection ii) Established neurological/degene