BCAA vs. Rifaximin in Patients With Cirrhosis for Secondary Prophylaxis of HE
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-65
SponsorPost Graduate Institute of Medical Education and Research, Chandigarh
About this 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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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.
Patients with active hepatocellular carcinoma or history of hepatocellular carcinoma that is in remission for less than six months.
Trial design
Design model
Parallel
Treatments tested in this trial
Oral Branched chain Amino acid
DrugThe active drug BCAA supplement will be dispensed in a dose of 15 gm once daily x 12 weeks
Rifaximin 550 MG
DrugActive drug rifaximin will be dispensed in a dose of 550mg twice daily x 12 weeks
Lactulose
DrugBoth 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
Placebo for BCAA
DrugA placebo comparator of 15 gm of skimmed milk powder will be used.
Placebo for Rifaximin 550mg
DrugIdentical placebo sugar pills will be used as a placebo.
Treatment groups
336 Participants
are divided into 2 treatment groupsGroup A: A1=Experimental:Experimental treatment 3 interventions
Group B: A2= Experimental:Experimental treatment 3 interventions
Trial outcomes
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
Time frame
24 WeeksSecondary outcomes
1
Computerized Cognitive Test battery for Cognitive performance
A curated Computer based Cognitive test battery has been created for this protocol with a fixed set of tasks comprising Animal Naming Test, reaction times, digit span and number connection tests. This has been designed using the PEBL opensource language. Psychology Experiment Building Language. \[2019-03\] PEBL Version 2.1. The battery has been validated by us previously in patients with chronic hepatitis C infection.
Time frame
At Enrolment2
Computerized Cognitive Test battery for Cognitive performance
Computerized Cognitive Test battery: A curated Computer based Cognitive test battery has been created for this protocol with a fixed set of tasks comprising Animal Naming Test, reaction times, digit span and number connection tests. This has been designed using the PEBL opensource language. Psychology Experiment Building Language. \[2019-03\] PEBL Version 2.1. The battery has been validated by us previously in patients with chronic hepatitis C infection.
Time frame
30 days3
Computerized Cognitive Test battery for Cognitive performance
Computerized Cognitive Test battery A curated Computer based Cognitive test battery has been created for this protocol with a fixed set of tasks comprising Animal Naming Test, reaction times, digit span and number connection tests. This has been designed using the PEBL opensource language. Psychology Experiment Building Language. \[2019-03\] PEBL Version 2.1. The battery has been validated by us previously in patients with chronic hepatitis C infection.
Time frame
90 days4
Psychiatric Assessment
Beck's Depression Inventory (BDI) test will be performed. The scoring is as follows 1-10: These ups and downs are considered normal 11-16: Mild mood disturbance 17-20: Borderline clinical depression 21-30: Moderate depression31-40: Severe depression 40: Extreme depression
Time frame
0 daysSponsors and contacts
Click on the lead sponsor to view all of their trials.
Post Graduate Institute of Medical Education and Research, Chandigarh
Lead sponsor
Indian Council of Medical Research
Collaborator
Source ClinicalTrials.gov