| CTRI Number |
CTRI/2025/03/082362 [Registered on: 17/03/2025] Trial Registered Prospectively |
| Last Modified On: |
02/08/2025 |
| Post Graduate Thesis |
Yes |
| Type of Trial |
Interventional |
|
Type of Study
|
Medical Device |
| Study Design |
Randomized, Parallel Group, Active Controlled Trial |
|
Public Title of Study
|
A study to understand whether exchanging blood plasma in high volume is better than standard volume for children with acute liver failure and altered sensorium |
|
Scientific Title of Study
|
An open label pilot RCT to demonstrate the superiority of high volume over standard volume therapeutic plasma exchange in pediatric patients with acute liver failure and hepatic encephalopathy |
| Trial Acronym |
NIL |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Aditya Gupta |
| Designation |
Doctor (Junior Resident) |
| Affiliation |
All India Institute of Medical Sciences New Delhi |
| Address |
Department of Pediatrics, Mother and Child Block, All India Institute of Medical Sciences Ansari Nagar, New Delhi, India
South
DELHI
110029
India |
| Phone |
9711539303 |
| Fax |
|
| Email |
aditya.g18@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Aditi Sinha |
| Designation |
Doctor (Additional Professor) |
| Affiliation |
All India Institute of Medical Sciences New Delhi |
| Address |
Room Number 802, Mother and Child Block, Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences Ansari Nagar, New Delhi, India
South
DELHI
110029
India |
| Phone |
9899145489 |
| Fax |
|
| Email |
aditisinhaaiims@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Aditi Sinha |
| Designation |
Doctor (Additional Professor) |
| Affiliation |
All India Institute of Medical Sciences New Delhi |
| Address |
Room Number 802, Mother and Child Block, Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences Ansari Nagar, New Delhi, India
South
DELHI
110029
India |
| Phone |
9899145489 |
| Fax |
|
| Email |
aditisinhaaiims@gmail.com |
|
|
Source of Monetary or Material Support
|
| All India Institute of Medical Sciences Ansari Nagar, New Delhi, India
PIN CODE - 110029 |
|
|
Primary Sponsor
|
| Name |
Aditya Gupta |
| Address |
Department of Pediatrics, Mother and Child Block, All India Institute of Medical Sciences Ansari Nagar, New Delhi, India |
| Type of Sponsor |
Other [Self] |
|
|
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 Aditya Gupta |
All India Institute of Medical Sciences New Delhi |
Department of Pediatrics, Mother and Child Block, All India Institute of Medical Sciences Ansari Nagar, New Delhi, India
South
DELHI |
9711539303
aditya.g18@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institute Ethics Committee |
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 |
| Intervention |
High Volume Therapeutic Plasma Exchange |
Plasma exchange with 2-3 times the calculated plasma volume |
| Comparator Agent |
Standard Volume Therapeutic Plasma Exchange |
Plasma exchange with 1-1.5 times the calculated plasma volume |
|
|
Inclusion Criteria
|
| Age From |
4.00 Year(s) |
| Age To |
18.00 Year(s) |
| Gender |
Both |
| Details |
Children, both male and female, 4-18 years of age with:
Pediatric acute liver failure as defined by PALF – Study group as i) hepatic-based coagulopathy, defined as a prothrombin time (PT) ≥ 15 sec or international normalized ratio (INR) ≥ 1.5 not corrected by vitamin K in the presence of clinical hepatic encephalopathy (HE), or a PT ≥ 20 sec or INR ≥ 2.0 regardless of the presence or absence of clinical hepatic encephalopathy (HE); (ii) biochemical evidence of acute liver injury; (iii) and no known evidence of chronic liver disease
Interval from jaundice to encephalopathy 8-28 days
Therapeutic Plasma Exchange indicated by (i) INR ≥2.5 and (ii) hepatic encephalopathy of any grade (1-4)
Written informed parental consent (patient’s assent will not be feasible as he/she will be in hepatic encephalopathy) |
|
| ExclusionCriteria |
| Details |
Body weight less than or equal to 8 kg
Known chronic liver disease of any etiology
Presenting more than 2 weeks after the onset of acute liver failure
AB blood group
Prior enrollment in the study
Anticipated delay of more than 24 hours in initiating therapeutic plasma exchange
Hemodynamic instability despite use of 2 or more than 2 vasoactive drugs in maximum doses
Decision of physician to not escalate therapy |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Sequentially numbered, sealed, opaque envelopes |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| Proportion of patients surviving at day 14 from randomization |
At day 14 |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Change from baseline, to 24-hr after 1 session of membrane filtration based therapeutic plasma exchange (mTPE) (day 2-3), 24-hr after 3 sessions of mTPE (day 4-5), and on day 7, in:
i. Grade of hepatic encephalopathy;
ii. Pediatric logistic organ dysfunction (PELOD) score;
iii. Chronic Liver Failure Sequential Organ Failure Assessment (CLIF-SOFA);
iv. Children’s hospital of Los Angeles liver failure (CHALF) score
v. Serum bilirubin
vi. International normalized ratio of prothrombin
vii. Serum ammonia
|
24-hr after 1 session of mTPE (day 2-3), 24-hr after 3 sessions of mTPE (day 4-5), and on day 7 |
| Number and types of adverse events, including serious adverse events (SAE), CTCAE classification and WHO-UMC categorization of relatedness to TPE, by end of 3 mTPE sessions |
Ongoing monitoring |
| Feasibility of procedure, as determined by average plasma volumes truly exchanged with fresh frozen plasma (FFP) at the end of 3 mTPE sessions |
At the end of 3 mTPE sessions |
| Proportions with native liver survival |
At day 14 |
|
|
Target Sample Size
|
Total Sample Size="30"
Sample Size from India="30"
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
|
N/A |
|
Date of First Enrollment (India)
|
27/03/2025 |
| 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="1"
Months="10"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
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
|
Pediatric acute liver failure (PALF) is a
complex and rapidly progressive condition. Despite advancements in critical
care, it is associated with high morbidity and mortality in the absence of
liver transplant. In the Indian setting, liver transplant is rare. Hence,
extracorporeal liver support systems (ELSS) are used as bridge therapy to
prolong survival of the patient till the time transplant becomes feasible.
Sometimes, especially in drug or toxin associated ALF, patient can even recover
spontaneously with these therapies. Therapeutic plasma exchange (TPE) is one of
the most prevalent ELSS and is currently recommended by Indian Society
of Pediatric Gastroenterology, Hepatology, and Nutrition (ISPGHAN) as a bridge therapy to liver transplant in PALF.
However, there is no consensus regarding the volume of plasma that needs to be
used. Evidence on this topic from pediatric population is chiefly from
retrospective case series or cohorts. Moreover, patient having subacute or
chronic liver disease have not always been excluded in these studies. Hence, this
prospective randomized pilot study with strict inclusion criteria is planned to
compare standard volume (1-1.5 times) and high volume (2-3 times) TPE in
pediatric patients with ALF and hepatic encephalopathy in whom TPE is indicated.
The outcomes of the study will provide useful information on whether high
volume TPE is indeed necessary, or standard volume TPE is associated with
outcomes similar to high volume TPE, in patients with pediatric ALF and hepatic
encephalopathy in whom TPE is indicated. This information will provide evidence
to refine protocols for extracorporeal therapies for pediatric ALF. The study will
also inform whether performing TPE in high volumes is feasible or not.
|