Acute-On-Chronic Liver Failure, Hepatic Encephalopathy
Conditions
Keywords
Hepatic Encephalopathy, Acute-On-Chronic Liver Failure, Neurological Dysfunction, Metabolomics, Systemic Inflammations, Branch Chain Amino Acid, bispectral index, Cerebral edema, Lactulose
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.
Interventions
Intravenous branched chain amino acids will be given for 3 days to patients in experimental arm
DRUGLactulose
Oral lactulose will be given to patients in both arms
Sponsors
Amrita Institute of Medical Sciences & Research Center
Asian Institute of Gastroenterology, India
All India Institute of Medical Sciences, Bhubaneswar
Kalinga Institute of Medical Sciences, Bhubaneswar
Post Graduate Institute of Medical Education and Research, Chandigarh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind Placebo Controlled
Intervention model description
Prospective interventional cohort study
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18-75 years 2. Either gender 3. Patients with ACLF (CANONIC definition) of any etiology with HE ≥grade 2 as per West-Haven Criteria
Exclusion criteria
1. Those who do not consent to participate in the study 2. Patients with structural brain lesions or stroke 3. Inability to obtain informed consent from patient or relatives 4. Severe preexisting cardiopulmonary disease 5. Renal dysfunction (S. Creatinine ≥ 2mg/dL) 6. Pregnancy/Lactation 7. Post liver transplant patients 8. HIV infection 9. Patients who are on psychoactive drugs, like sedatives or antidepressants 10. Patients who are too sick to carry out the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Survival | Day 28 | Survival assessment will be made by recording all deaths |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Reduction of consciousness recovery time among survivors | Day 28 | Consciousness will be assessed by cognitive battery tests |
| Reduction of arterial ammonia Level | Day 3 | Level of ammonia will be measured by Point of care device |
| Improvement of encephalopathy by one or more grade | Day 7 | Improvement in scoring of hepatic Encephalopathy |
| Assessment of metabolomics following BCAA + Lactulose and Lactulose alone | Day 7 | Metabolomics will be performed by LC/GC-MS |
| 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 |
| Survival | Day 28 | Survival assessment will be done with recording all cause mortality |
Countries
India
Outcome results
None listed