| 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
|
|
|
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
|
|
|
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. |