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

Trial details

Who runs it

Post Graduate Institute of Medical Education and Research, Chandigarh

Trial code

NCT06538077

Record updated

10 June 2025

Original description

RationaleRead full original descriptionShow less

Branch Chain Amino Acids vs. Rifaximin in Patients With Cirrhosis for Secondary Prophylaxis of Hepatic Encephalopathy: Double-blind Placebo-controlled Multicentric Randomized Controlled Trial

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.

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

Exclusion: Conditions that can impact interpretation of cognitive function:; 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; Subjects with active bacterial or fungal infection; Subjects with active or very recent gastrointestinal bleeding in the last 2 weeks; Patients with active hepatocellular carcinoma or history of hepatocellular carcinoma that is in remission for less than six months; Patients with current extra hepatic malignancies, including solid tumours and hematologic disorders; 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; Current overt hepatic encephalopathy, defined as grade II-IV hepatic encephalopathy according to the West-Haven classification; 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; Pregnancy (urine pregnancy test at inclusion); Refusal or inability to give informed consent.

ClinicalTrials.gov NCT06538077