Intravenous BCAA for HE in ACLF (BCAA-HE-ACLF)
- Conditions
- Hepatic EncephalopathyAcute-On-Chronic Liver Failure
- Interventions
- Drug: Branch Chain Amino Acid
- Registration Number
- NCT05700695
- Lead Sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Brief Summary
This multi-centric study analyses the effect of intravenous branched-chain amino acids (BCAA) on overt HE in patients with ACLF. The investigators aim to study the efficacy of combining intravenous BCAA with lactulose versus lactulose alone, ammonia measures, endotoxin, metabolomics, and cerebral edema in the medical management of overt HE in patients with ACLF. The study will also access the impact on overall survival and improvement in the grade of HE.
- Detailed Description
Treatment of HE in ACLF is based on extrapolation of data available from cirrhotic patients with HE. The mainstay of treatment remains Lactulose. Rifaximin is added on to therapy who have a breakthrough episode of HE on lactulose. BCAA is used as an add-on therapy if patients have minimal/covert encephalopathy, are protein intolerant or have recurrent HE. No studies are available assessing the adjuvant effect of intravenous BCAA on ammonia reduction in HE in patients with ACLF. So, this study has been designed to analyze the effect of intravenous BCAA on hepatic encephalopathy in patients with ACLF. This study will also analyze the systemic and neuronal inflammation, metabolomics, and cerebral edema under the effect of intravenous BCAA in HE patients with ACLF.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 226
- Age 18-75 years
- Either gender
- Patients with ACLF (CANONIC definition) of any etiology with HE ≥grade 2 as per West-Haven Criteria
- Those who do not consent to participate in the study
- Patients with structural brain lesions or stroke
- Inability to obtain informed consent from patient or relatives
- Severe preexisting cardiopulmonary disease
- Renal dysfunction (S. Creatinine ≥ 2mg/dL)
- Pregnancy/Lactation
- Post liver transplant patients
- HIV infection
- Patients who are on psychoactive drugs, like sedatives or antidepressants
- Patients who are too sick to carry out the protocol.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experiential Arm Branch Chain Amino Acid Drug: iv Branch Chain Amino Acid + Lactulose Intravenous Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose Experiential Arm Lactulose Drug: iv Branch Chain Amino Acid + Lactulose Intravenous Branched Chain Amino Acids - 500mL once daily for 3 days plus Lactulose Comparator Arm Lactulose Drug: Lactulose + Placebo
- Primary Outcome Measures
Name Time Method Survival Day 28 Survival assessment will be made by recording all deaths
- Secondary Outcome Measures
Name Time Method Reduction of consciousness recovery time among survivors Day 28 Consciousness will be assessed by cognitive battery tests
Improvement of encephalopathy by one or more grade Day 7 Improvement in scoring of hepatic Encephalopathy
Reduction of arterial ammonia Level Day 7 Level of ammonia will be measured by Point of care device
Assessment of cerebral edema Discharge form Hospital and 3 month of episode of HE Cerebral edema will be assessed by Magnetic Resonance Imaging+ Magnetic Resonance Spectroscopy
Prevention/reduction of cerebral edema based on optic nerve sheath diameter (ONSD) 72 Hours ONSD measurement will be done by Ultrasound
Assessment of metabolomics following BCAA + Lactulose and Lactulose alone Day 7 Metabolomics will be performed by LC/GC-MS
Survival Day 90 Survival assessment will be done with recording all cause mortality
Dynamic Assessment of systemic inflammation (Cytokines: IL-1b, IL-6, INF-g, TNF-a, IL-15, IL-17, IL-18) at presentation and after Specific management. Day 0 Systemic inflammation will be accessed by Cytometric Bead Array
Trial Locations
- Locations (1)
Dr. Madhumita Premkumar
🇮🇳Chandigarh, India