- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05778461
Efficacy of L-ornithine L-aspartate and Therapeutic Plasma Exchange Versus Plasma Exchange Alone in Lowering Ammonia and Improving Outcomes in Pediatric Acute Liver Failure.
Efficacy of L-ornithine L-aspartate and Therapeutic Plasma Exchange Versus Plasma Exchange Alone in Lowering Ammonia and Improving Outcomes in Pediatric Acute Liver Failure: A Randomized Controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Methodology:
- Study population
Pediatric acute liver failure patients aged 5-18 years of age, INR > 2, Hepatic encephalopathy (defined by West Haven criteria) and arterial ammonia >100mcg/dL
Study Design:
Interventional - Placebo controlled RCT.
Allocation: Randomized
Method of randomization: Block randomization using Interactive Web Response System (IWRS) with block size 4
Intervention Model: Parallel Assignment
Masking: Double. Patients and investigators will be blinded to treatment assignments. Both intervention and placebo will be prepared and administered by trial nurse.
- Study period
24 months (Feb 2023-Feb 2025)
-- Sample size
As this is a pilot study, a sample size of 16 patients in each arm will be taken.
- Intervention
- In Intervention Arm 1 LOLA will be administered via continuous intravenous infusion at a dosage of 0.75g/kg/day for 72h (maximum 30g/day). High volume plasma exchange (2x plasma volume) will be started at least 8 hours after initiation of LOLA, and will be completed within 4-5 hours depending on the volume of exchange. Three consecutive cycles of HVPE will be performed, starting at 8h, 32h and 56h respectively. In Control Arm, placebo will be administered via continuous infusion for 72h, along with HVPE (2x plasma volume) starting at 8h, 32h and 56h respectively. Placebo will be procured from the same pharmaceutical company manufacturing LOLA. Patients and investigators will be blinded to treatment assignments. Both intervention and placebo will be prepared and administered by trial nurse.
- STATISTICAL ANALYSIS:
- Primary outcome measure: Mann -Whitney U test
Secondary outcome measures
- Fisher's exact test for categorical data
- Mann-Whitney U test for continuous data
- IBM® SPSS® Statistics 29 will be used for statistical analysis. P<0.05 will be considered as statistically significant.
- Adverse effects
- Stopping rule
Interim analysis will be done after 16 patients. If significant increase in mortality or worsening grade of encephalopathy is seen in the LOLA arm, trial will be stopped. The trial will also be stopped if any significant safety signals related to the adverse effect profile of the study drug is identified in the interim analysis.
(c) Expected outcome of the project:
The investigators expect LOLA and therapeutic plasma exchange will act synergistically to lower ammonia more effectively and this lowering of ammonia will lead to better native liver survival among children with acute liver failure.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Dr Tamoghna Biswas, MD
- Phone Number: 7439983747
- Email: tamoghnab@gmail.com
Study Contact Backup
- Name: Dr Bikrant Bihari Lal, DM
- Phone Number: 9540951063
- Email: bikrant18may@gmail.com
Study Locations
-
-
-
New Delhi, India, 110070
- Institute of liver and Biliary Sciences
-
Contact:
- Tamoghna Biswas, MD
- Phone Number: 7439983747
- Email: tamoghnab@gmail.com
-
Contact:
- Bikrant Bihari Lal, DM
- Phone Number: 9540951063
- Email: bikrant18may@gmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Pediatric Acute Liver Failure as defined by PALF-Study Group
- 5-18 years of age
- INR > 2
- Hepatic encephalopathy (defined by West Haven criteria)
- Ammonia >100mcg/dL
Exclusion Criteria:
- Irreversible neurological injury
- Previous treatment with LOLA within 48 hours before admission.
- Acute kidney injury.
- Acute on chronic liver failure
- Those not giving consent
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: L-ornithine L-Aspartate
LOLA will be administered via continuous intravenous infusion at a dosage of 0.75g/kg/day for 72h (maximum 30g/day).
High volume plasma exchange (2x plasma volume) will be started at least 8 hours after initiation of LOLA, and will be completed within 4-5 hours depending on the volume of exchange.
Three consecutive cycles of HVPE will be performed, starting at 8h, 32h and 56h respectively.
|
LOLA will be administered via continuous intravenous infusion at a dosage of 0.75g/kg/day for 72h (maximum 30g/day).
High volume plasma exchange (2x plasma volume) will be started at least 8 hours after initiation of LOLA, and will be completed within 4-5 hours depending on the volume of exchange.
Three consecutive cycles of HVPE will be performed, starting at 8h, 32h and 56h respectively.
|
Placebo Comparator: Placebo
Placebo will be administered via continuous infusion for 72h, along with HVPE (2x plasma volume) starting at 8h, 32h and 56h respectively.
|
Placebo will be administered via continuous infusion for 72h, along with HVPE (2x plasma volume) starting at 8h, 32h and 56h respectively.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Comparison of change in ammonia (baseline to day 3) in the 2 groups
Time Frame: 72 hours
|
72 hours
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Comparison of proportion of participants dying by Day 7 and Day 14 between two groups
Time Frame: Days 7 and 14
|
Days 7 and 14
|
Comparison of proportion of participants requiring liver transplant by Day 7 and Day 14 between two groups
Time Frame: Day 7 and Day 14
|
Day 7 and Day 14
|
Comparison of overall survival at Day 7 and Day 14 between two groups
Time Frame: Days 7 and 14
|
Days 7 and 14
|
Comparison of change in grade of encephalopathy assessed by West Haven scale by day 3 and day 7
Time Frame: Day 3 and Day 7
|
Day 3 and Day 7
|
Comparison of optic nerve sheath diameter measured by ultrasound at 24,48 and 72 hours in the 2 groups
Time Frame: 24 hours, 48 hours and 72 hours
|
24 hours, 48 hours and 72 hours
|
To compare the cumulative requirement of mannitol and propofol in the first 72 hours in the 2 groups
Time Frame: 72 hours
|
72 hours
|
Comparison of plasma and dialysate glutamine levels after first cycle of High Volume Plasma Exchange between two groups
Time Frame: 72 hours
|
72 hours
|
Comparison of number of episodes of clinically raised intracranial pressure in the 2 groups
Time Frame: 72 hours
|
72 hours
|
Compare the adverse events in the 2 groups
Time Frame: 72 hours
|
72 hours
|
Collaborators and Investigators
Investigators
- Principal Investigator: Dr Tamoghna Biswas, MD, Institute of liver and Biliary Sciences
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ILBS-ALF-06
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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