Comparing BCAA and Rifaximin for Preventing Hepatic Encephalopathy Recurrence

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

This study is testing whether taking branched-chain amino acids or rifaximin can help people who have recently recovered from liver-related brain issues avoid having those problems come back.

Quick facts

• Phase: PHASE4
• Study type: Interventional
• Enrollment: 336 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh (other)
• Locations: 1 site (Chandigarh)
• Trial ID: NCT06538077 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness of oral branched-chain amino acids (BCAA) versus rifaximin in preventing recurrent episodes of hepatic encephalopathy (HE) in patients who have recently recovered from overt HE. Conducted across multiple centers in India, the trial employs a double-blind, placebo-controlled design to minimize bias and accurately assess cognitive function improvements. Participants will receive either BCAA or rifaximin alongside lactulose, with the primary objective being to determine the first breakthrough episode of HE within six months. The study aims to address the high recurrence rates of HE and improve overall patient health and cognitive function.

Who should consider this trial

Good fit: Ideal candidates for this study are patients with cirrhosis who have recently been discharged from the hospital after an episode of overt hepatic encephalopathy.

Not a fit: Patients currently experiencing active hepatic encephalopathy or those with certain neurological conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a more effective secondary prophylaxis for patients recovering from hepatic encephalopathy, potentially improving their cognitive function and quality of life.

How similar studies have performed: While there have been studies on the management of hepatic encephalopathy, this head-to-head comparison of BCAA and rifaximin as secondary prophylaxis is a novel approach.

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/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
5. Patients with active hepatocellular carcinoma or history of hepatocellular carcinoma that is in remission for less than six months.
6. 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.
7. Patients with current extra hepatic malignancies, including solid tumours and hematologic disorders.
8. Patients with MELD\>20
9. 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.
10. Patients with TIPS shunt in situ
11. Pregnancy (urine pregnancy test at inclusion)
12. Refusal or inability to give informed consent

Where this trial is running

Chandigarh

• PGIMER — Chandigarh, India (RECRUITING)

Study contacts

• Study coordinator: Madhumita Premkumar

Conditions: Hepatic Encephalopathy, Decompensated Cirrhosis, Minimal Hepatic Encephalopathy, Hepatic encephalopathy, Branched-chain amino acids, Computerized neurocognitive test battery, Double blind placebo controlled multicentric randomized controlled trial, rifaximin