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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.

NCT05778461 · Status: UNKNOWN · Phase: NA · Type: INTERVENTIONAL · Enrollment: 32

Last updated 2023-03-21

No results posted yet for this study

Summary

Pediatric acute liver failure (PALF) is associated with very high mortality and morbidity with native liver survival varying between 21 to 75%.Hyperammonemia manifesting as hepatic encephalopathy and causing cerebral edema isresponsible for poor neurological outcome in ALF. Ammonia lowering measures have led to improvement in HE and higher native liver survival. L-ornithine L-aspartate (LOLA), a salt of natural amino-acids ornithine and aspartate, is an importantammonia scavenging drug. It acts as a substrate for urea cycle in liver and also converts ammonia to glutamine in perivenous hepatocytes as well as in the muscles.This drug has been shown to reduce ammonia and improve hepatic encephalopathy in cirrhoticadults.However, the issue with this drug is that the glutamine formed can reconvert to ammonia by the action of glutaminase, possibly, the reason why it failed to show decrease in ammonia and improvement in native liver survival in a randomized controlled trial in adult ALF. In western countries, ornithine phenylacetate has been used where ornithine converts ammonia to glutamine and phenylacetate then binds to this glutamine to form phenylacetylgutamine and eliminates it. Therapeutic plasma exchange (TPE), both high volume and standard volume has been shown to improve native liver survival in adults with ALF and is the standard of care in management of ALF and a grade 1 recommendation by all eminent liver societies.TPE leads to decreased ammonia. Although rate of ammonia formation is multiple times higher than rate of ammonia removal by plasmapheresis, this ammonia reduction is an indirect effect of glutamine removal by TPE. Glutamine, thus, acts as a reservoir for clearance of ammonia (in muscles and perivenous hepatocytes).In contrast to adults, the response to therapeutic plasma exchange has not been as encouraging inchildren, yet, most centers continue to use it based on recommendations in adults. Based on the knowledge that LOLA converts ammonia to glutamine and TPE clears glutamine from plasma, the investigators hypothesize that LOLA would act in synergestic way with TPE to lower ammonia levels, resulting in improvement in HE and better native liver survival in pediatric ALF. The goal of this clinical trial is to compare L-ornithine L-aspartate and therapeutic plasma exchange versus plasma exchange alone in lowering ammonia and improving outcomes in patients with pediatric acute liver failure.

Conditions

  • Liver Failure, Acute

Interventions

DRUG

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.

DRUG

Placebo

Placebo will be administered via continuous infusion for 72h, along with HVPE (2x plasma volume) starting at 8h, 32h and 56h respectively.

Sponsors & Collaborators

  • Institute of Liver and Biliary Sciences, India

    lead OTHER

Principal Investigators

  • Dr Tamoghna Biswas, MD · Institute of Liver and Biliary Sciences

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Model
PARALLEL

Eligibility

Min Age
5 Years
Max Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2023-03-15
Primary Completion
2024-10-30
Completion
2024-10-30

Countries

  • India

Study Locations

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Entities

Drugs

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT05778461 on ClinicalTrials.gov