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CTRI Number  CTRI/2025/01/079008 [Registered on: 20/01/2025] Trial Registered Prospectively
Last Modified On: 17/01/2025
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Drug
Biological 
Study Design  Randomized, Parallel Group, Active Controlled Trial 
Public Title of Study   Standard Volume (biological procedure) vs. High Volume Plasma Exchange (biological procedure) in Pediatric Acute Liver Failure (Disease). 
Scientific Title of Study   Standard Volume vs. High Volume Plasma Exchange in Pediatric Acute Liver Failure-A Pilot Randomized Control trial. 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
None  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Ashray S Patel 
Designation  Senior Resident,Department of Pediatric Hepatology 
Affiliation  Institute of Liver and Biliary Sciences 
Address  Room No. 3317, Department of Hepatology, Phase II, 3rd Floor, D-1, Vasant Kunj, New Delhi-110070.

South West
DELHI
110070
India 
Phone  01146300000  
Fax    
Email  patel1995ash@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Vikrant Sood 
Designation  Additional Professor, Department of Pediatric Hepatology  
Affiliation  Institute of Liver and Biliary Sciences 
Address  Room No. 3317, Department of Hepatology, Phase II, 3rd Floor, D-1, Vasant Kunj, New Delhi-110070.

South West
DELHI
110070
India 
Phone  01146300000  
Fax    
Email  drvickyster@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Vikrant Sood 
Designation  Additional Professor, Department of Pediatric Hepatology  
Affiliation  Institute of Liver and Biliary Sciences 
Address  Room No. 3317, Department of Hepatology, Phase II, 3rd Floor, D-1, Vasant Kunj, New Delhi-110070.


DELHI
110070
India 
Phone  01146300000  
Fax    
Email  drvickyster@gmail.com  
 
Source of Monetary or Material Support  
ILBS,D-1,Vasant Kunj,New Delhi-110070. 
 
Primary Sponsor  
Name  Institute of Liver and Biliary Sciences 
Address  D-1,Vasant Kunj,New Delhi-110070. 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Ashray S Patel  Institute of Liver and Biliary Sciences  Room No. 3317, Department of Hepatology, Phase II, 3rd Floor, D-1, Vasant Kunj, New Delhi-110070.
South West
DELHI 
01146300000

patel1995ash@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional Ethics Committee, ILBS  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: K720||Acute and subacute hepatic failure,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  HV TPE-Therapeutic Plasma Excahnge with Standard Medical treatment.   HV PLEX 2-2.3 times plasma volume. Route: Intravenous Duration : 3 days 
Intervention  SV-Therapeutic Plasma Excahnge with Standard Medical treatment  SV PLEX 1.3-1.5 times plasma volume. Route: Intravenous Duration : 3 days 
 
Inclusion Criteria  
Age From  3.00 Year(s)
Age To  18.00 Year(s)
Gender  Both 
Details  1. Age: 3 years to 18 years
2. Fulfilling PALFSG definition
3. Baseline INR more than equals to 2.5, and increasing INR (any value) and/or worsening hepatic. encephalopathy (more than 1 grade change) after 6 to 12 hours of standard medical therapy. 
 
ExclusionCriteria 
Details  1. Disseminated intravascular coagulation
2. Marked hemodynamic instability requiring a high dose of vasopressors (norepinephrine more than 0.5 mcg per kg per min)
3. Signs of irreversible brain injury
4. Any severe cardio-pulmonary pre-existing disease
5. Septic Shock 
 
Method of Generating Random Sequence   Permuted block randomization, fixed 
Method of Concealment   Centralized 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
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  
Outcome  TimePoints 
Clinical parameters: ONSD (Left/Right), Mean arterial pressure, Grades of HE from day 0 to day 4  Day 0,Day1,Day2,day3,Day 4 
Biochemical parameters: LFT, International normalized ratio, Arterial ammonia, Arterial lactate, from day 0 to day 4.  Day 0,Day1,Day2,day3,Day 4 
Patient with Cytokines level at day 0 and day 3: Pro-Inflammatory (TNF Alpha, IL-6, IL-1b) & Anti-Inflammatory Cytokines (IL-4, IL-10)  Day 0 & 3 
Impact on other factors at day 0 and 3: Growth Factors (G-CSF),Damage Associated Molecular Pattern (DAMPS) (S100B, HMGB1),Von Willebrand Factor.  Day 0 & 3 
Adverse effects: Hemodynamic instability, Metabolic alkalosis, Thrombocytopenia/Drop in Hb, Sepsis, Hypocalcemia, Circulatory Overload, TRALI.
 
Day 21 
Duration of mechanical ventilation & ICU stay.  Day 21 
Mortality/Liver Transplant  Day 21 
 
Target Sample Size   Total Sample Size="40"
Sample Size from India="40" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 2/ Phase 3 
Date of First Enrollment (India)   28/01/2025 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

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.

 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. 
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