Standard Volume vs. High Volume Plasma Exchange in Pediatric Acute Liver Failure

Standard Volume vs. High Volume Plasma Exchange in Pediatric Acute Liver Failure - A Pilot Randomized Control Trial

Acute liver failure is a multisystem disorder characterized by a syndrome of jaundice, coagulopathy, and encephalopathy with high mortality in the absence of liver transplantation. The pathogenesis of multiorgan failure (MOF) in ALF has been attributed to the release of damage-associated molecular patterns (DAMPs) from injured hepatic cells and microbial pathogen-associated molecular patterns (PAMPs) in the presence of superimposed infection or bacterial translocation.The innate immune cells activated by PAMPs and DAMPs produce pro-inflammatory cytokines [interleukin (IL)-6, IL-1b, IL-8, tumor necrosis factor-alpha (TNF-a)]. Studies indicate that the removal of inflammatory mediators appears to play a role in the treatment of ALF and are removed by some apheresis techniques. Hence therapeutic exchange (TPE) has been used as adjunct or standalone therapy for bridging patients to recovery or LT. TPE to treat liver failure involves two steps-removal of plasma from a patient with liver failure and replacing this with equal volume of fluid; in view of the coagulopathy seen in liver failure patients, the preferred fluid for replacement is fresh frozen plasma. Different doses of PLEX have been used to treat liver failure patients with high, standard or low volume PLEX, to treat ALF. Presently American Apheresis Society guidelines consider High Volume TPE (HV-TPE) as first line the management of ALF. But HV-TPE, apart from strain on blood bank resources (large volumes of fresh frozen plasma needed), also carries risk of transfusion associated acute lung complications, risk of blood borne virus infection, and so on make the use of low-volume PLEX attractive compared to high-volume PLEX. Hence this study is being carried out to consider the safety and efficacy of standard volume plasma exchange (SV-TPE) vs. HV-TPE in Pediatric ALF.

Study Overview

• Status: Recruiting
• Conditions: Acute Liver Failure
• Intervention / Treatment: Drug: Standard Medical treatment; Biological: Therapeutic Plasma Excahnge

Detailed Description

Aim: To study the efficacy in terms of the native liver survival, of standard volume plasma exchange as compared to high volume plasma exchange in Pediatric ALF.

Study Design: Open label pilot Randomized Control trial. Sample size: Time bound. All cases presenting during the study period will be included in the study.

Standard Medical Therapy:

• All patients are were managed by a multidisciplinary team at Live Coma ICU.
• Intubation and ventilation were undertaken for standard indications in addition to the development of grade 3 encephalopathy or evidence of cerebral edema
• Ventilation was managed by fentanyl and propofol along with the use of atracurium for paralysis wherever required.
• Hemodynamics, ONSD and TCD are monitored routinely.
• All patients received N-acetylcysteine.
• Neuro-protective measures such as hypertonic saline, head end elevation, minimal stimulation, propofol and thiopentone infusion are followed as per protocol.
• Anti-ammonia measures like sodium benzoate, CRRT as well started as per protocol.
• CRRT is done for routine renal indications, hyperlactetmia, hyperammonemia.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr Vikrant Sood, DM; Phone Number: 01146300000; Email: drvickyster@gmail.com
• Study Contact Backup: Name: Dr Ashray S Patel, MD; Phone Number: 01146300000; Email: patel1995ash@gmail.com

Study Locations

• India
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110070
      • Recruiting
      • Institute of Liver & Biliary Sciences
      • Contact: Dr Ashray S Patel, MD; Phone Number: 01146300000; Email: patel1995ash@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 3 years to 18 years
2. Fulfilling PALFSG definition (J Pediatr. 2006 May;148(5):652-658).
3. Baseline INR ≥ 2.5, and increasing INR (any value) and/or worsening hepatic. encephalopathy (> 1 grade change) after 6 to 12 hours of standard medical therapy.

Exclusion Criteria:

1. Disseminated intravascular coagulation
2. Marked hemodynamic instability requiring a high dose of vasopressors (norepinephrine >0.5 mcg/kg/min)
3. Signs of irreversible brain injury
4. Any severe cardio-pulmonary pre-existing disease
5. Septic Shock

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SV-TPE group	Drug: Standard Medical treatment; Standard Medical treatment; Biological: Therapeutic Plasma Excahnge; Therapeutic Plasma Excahnge
Active Comparator: HV- TPE group	Drug: Standard Medical treatment; Standard Medical treatment; Biological: Therapeutic Plasma Excahnge; Therapeutic Plasma Excahnge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Native liver survival at day 21, in patients receiving standard volume (1.3-1.5 times plasma volume) therapeutic plasma exchange and those receiving high volume (2-2.2 times plasma volume) therapeutic plasma exchange in children with acute.	Day 21

Secondary Outcome Measures

Outcome Measure	Time Frame
Clinical parameters:Grades of Hepatic Encephalopathy from day 0 to day 4.	Day 0,Day1,Day2,day3,Day 4
Clinical parameters: Optic Nerve Sheet Diameter (Left/Right) from day 0 to day 4.	Day 0,Day1,Day2,day3,Day 4
Clinical parameters: Mean arterial pressure from day 0 to day 4.	Day 0,Day1,Day2,day3,Day 4
Proportion of patients with change in Liver Function test from day 0 to day 4.	Day 0,Day1,Day2,day3,Day 4
Biochemical parameters: International normalized ratio from day 0 to day 4.	Day 0,Day1,Day2,day3,Day 4
Biochemical parameters:Arterial ammonia from day 0 to day 4.	Day 0,Day1,Day2,day3,Day 4
Biochemical parameters: Arterial lactate from day 0 to day 4.	Day 0,Day1,Day2,day3,Day 4
Patient with change in Cytokines level at day 0 and day 3.	Day 0 & Day 3
Impact on other factors at day 0 and 3: Growth Factors (G-CSF).	Day 0 & Day 3
Impact on other factors at day 0 and 3: Damage Associated Molecular Pattern (DAMPS) (S100B, HMGB1).	Day 0 & Day 3
Impact on other factors at day 0 and 3: Von Willebrand Factor.	Day 0 & Day 3
Adverse effects in both groups	Within Day 21
Duration of mechanical ventilation & ICU stay.	Within Day 21
Mortality	Within Day 21
Number of participants with Liver Transplant	Within Day 21

Collaborators and Investigators

• Sponsor: Institute of Liver and Biliary Sciences, India

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 3, 2025
• First Submitted That Met QC Criteria: February 15, 2025
• First Posted (Actual): February 18, 2025

Study Record Updates

• Last Update Posted (Actual): January 6, 2026
• Last Update Submitted That Met QC Criteria: December 31, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Liver Failure, Acute
• Other Study ID Numbers: ILBS-ALF-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No