Effect of Goal Directed Ammonia Lowering Therapy in Acute on Chronic Liver Failure Patients With Hepatic Encephalopathy.

Study Overview
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Brief Summary
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In this study, all patients with ACLF (Acute on Chronic Liver Failure) with grade III/IV HE (Hepatic Encephalopathy) getting admitted in our institute will be enrolled after the fulfilment of inclusion/exclusion criteria and consent of the patient's attendants. Investigation of the patient (as mentioned in the proforma) will be done. Intervention step 1: liq Lactulose 100 mL stat followed by 30 mL/ hourly through NG/NJ route + Lactulose enema 3rd hourly - till 4 time soft stool is passed, then 30 mL through enteral route 6th hourly (If patient has no bowel sounds, only enema will be given) Intervention step 2: (after 24 hours of introduction of step 1, if no rapid reduction in ammonia to <70mcg/dL) Randomization to L or R arm R Arm (Addition of Rifaximin) Continuation of Lactulose + addition of Rifaximin 400 mg 8th hourly through enteral route L Arm (Lactulose only) Continuation of Lactulose therapy for further 48 hours.

Conditions
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Acute-On-Chronic Liver Failure

Intervention / Treatment
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* Drug: Lactulose + Rifaximin
* Drug: Lactulose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years and above Patients with ACLF with grade III/IV HE Exclusion Criteria: Patients with prior decompensation Grade I,II HE Chronic HE CV stroke Patients with ammonia level <70 mcg/dL Patients with Septic shock Pregnant lady

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lactulose + Rifaximin<br>Continuation of Lactulose + addition of Rifaximin 400 mg 8th hourly through enteral route. | Drug: Lactulose + Rifaximin<br>* Lactulose + addition of Rifaximin 400 mg 8th hourly through enteral route<br>|
| Active Comparator: Lactulose therapy<br> | Drug: Lactulose<br>* Continuation of Lactulose therapy for further 48 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of ammonia level to <70 mcg/dL within 72 hours of the ammonia reduction treatment. |  | 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of ammonia level to at least 50% of the baseline value within 72 hours. |  | 3 days | 
| Duration of hepatic encephalopathy post-inclusion. | 10 days after enrollment or 7 days after achieving primary endpoint, whichever is shorter. | 10 days | 
| Improvement in hepatic encephalopathy from grade III-IV to II-I at any time within 72 hours of treatment. |  | 3 days | 
| Liver disease related and overall mortality. | 10 days after enrollment or 7 days after achieving primary endpoint, whichever is shorter. | 10 days | 
| Duration of ICU stay. | 10 days after enrollment or 7 days after achieving primary endpoint, whichever is shorter. | 10 days |