High Volume Plasma Exchange in Children With Acute Liver Failure and Acute on Chronic Liver Failure

Study Overview
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Brief Summary
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All the children with acute liver failure who are candidates for transplant but have constraints for transplant will be randomized either to receive standard medical therapy or high volume plasma exchange along with standard medical therapy with the aim to assess the effect of high volume plasma exchange on transplant free survival.

Official Title
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High Volume Plasma Exchange in Children With Acute Liver Failure and Acute on Chronic Liver Failure-A Prospective Pilot Study.

Conditions
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Acute Liver Failure

Intervention / Treatment
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* Biological: High Volume Plasma Exchange
* Drug: Hypertonic 3% saline
* Drug: Mannitol
* Device: Elective positive pressure ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Children ≥ 10kg with ALF with INR ≥ 4 or INR ≥ 3 with Hepatic Encephalopathy. Exclusion Criteria: Evidence of active infection (Age specific neutrophilic leucocytosis (ANC) and procalcitonin ≥ 2 and/or focus of active infection Refusal of consent or assent (annexure 3) Liver resections with liver failure Patients with clinical suspicion of irreversible brain injury Patients with acute kidney injury

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Volume Plasma Exchange with Standard Treatment<br> | Biological: High Volume Plasma Exchange<br> <br> |
| Active Comparator: Standard Treatment<br>Standard Treatment is defined as anti raised Intra-cranial pressure Elective positive pressure ventilation in hepatic encephalopathy grade 3 or 4 and in those with features of raised ICP (Intra-cranial pressure). Mannitol Hypertonic 3% Saline | Drug: Hypertonic 3% saline<br> <br> Drug: Mannitol<br> <br> Device: Elective positive pressure ventilation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transplant free Survival. |  | 7 days | 
| Transplant free survival |  | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival after liver transplant with or without High Volume Plasma Exchange. |  | 30 days post procedure | 
| Incidence of organ dysfunction (other than liver and Central Nervous System). |  | 30 days | 
| Number of organs (other than liver and CNS) affected in children with organ dysfunction. |  | 30 days | 
| Incidence of High Volume Plasma Exchange related complications- Major/Minor. |  | within 1 month | 
| Change in hemodynamic parameters and Hepatic Encephalopathy (HE) before and after in the High Volume Plasma Exchange group. |  | 0 day | 
| Change in hemodynamic parameters and Hepatic Encephalopathy (HE) before and after in the High Volume Plasma Exchange group. |  | 5 days | 
| Change in Laboratory parameters - Bilirubin, INR and Ammonia in control group. |  | 0 day | 
| Change in Laboratory parameters - Bilirubin, INR and Ammonia- in control group. |  | 5 day | 
| Change in the levels of IL-6 and TNF alpha (Tumor Necrosis Factor) in HVPE arm from baseline till within 24-hours of the last session of High Volume Plasma Exchange. |  | within 24-hours of the last session of High Volume Plasma Exchange | 
| Change in the levels of IL-6 and TNF alpha (Tumor Necrosis Factor) in control arm from baseline till 5 days. |  | 5 days |