Ignite Creation Date:
2025-12-24 @ 12:10 PM
Ignite Modification Date:
2025-12-30 @ 12:06 PM
Study NCT ID:
NCT05778461
Status:
UNKNOWN
Last Update Posted:
2023-03-21
First Post:
2023-02-08
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
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.
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D017114', 'term': 'Liver Failure, Acute'}], 'ancestors': [{'id': 'D017093', 'term': 'Liver Failure'}, {'id': 'D048550', 'term': 'Hepatic Insufficiency'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C002939', 'term': 'ornithylaspartate'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 32}}, 'statusModule': {'overallStatus': 'UNKNOWN', 'lastKnownStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2023-03-15', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-02', 'completionDateStruct': {'date': '2024-10-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-03-09', 'studyFirstSubmitDate': '2023-02-08', 'studyFirstSubmitQcDate': '2023-03-09', 'lastUpdatePostDateStruct': {'date': '2023-03-21', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2023-03-21', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2024-10-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Comparison of change in ammonia (baseline to day 3) in the 2 groups', 'timeFrame': '72 hours'}], 'secondaryOutcomes': [{'measure': 'Comparison of proportion of participants dying by Day 7 and Day 14 between two groups', 'timeFrame': 'Days 7 and 14'}, {'measure': 'Comparison of proportion of participants requiring liver transplant by Day 7 and Day 14 between two groups', 'timeFrame': 'Day 7 and Day 14'}, {'measure': 'Comparison of overall survival at Day 7 and Day 14 between two groups', 'timeFrame': 'Days 7 and 14'}, {'measure': 'Comparison of change in grade of encephalopathy assessed by West Haven scale by day 3 and day 7', 'timeFrame': 'Day 3 and Day 7'}, {'measure': 'Comparison of optic nerve sheath diameter measured by ultrasound at 24,48 and 72 hours in the 2 groups', 'timeFrame': '24 hours, 48 hours and 72 hours'}, {'measure': 'To compare the cumulative requirement of mannitol and propofol in the first 72 hours in the 2 groups', 'timeFrame': '72 hours'}, {'measure': 'Comparison of plasma and dialysate glutamine levels after first cycle of High Volume Plasma Exchange between two groups', 'timeFrame': '72 hours'}, {'measure': 'Comparison of number of episodes of clinically raised intracranial pressure in the 2 groups', 'timeFrame': '72 hours'}, {'measure': 'Compare the adverse events in the 2 groups', 'timeFrame': '72 hours'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Liver Failure, Acute']}, 'descriptionModule': {'briefSummary': '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.', 'detailedDescription': "Methodology:\n\n\\- Study population\n\nPediatric acute liver failure patients aged 5-18 years of age, INR \\> 2, Hepatic encephalopathy (defined by West Haven criteria) and arterial ammonia \\>100mcg/dL\n\nStudy Design:\n\nInterventional - Placebo controlled RCT.\n\nAllocation: Randomized\n\nMethod of randomization: Block randomization using Interactive Web Response System (IWRS) with block size 4\n\nIntervention Model: Parallel Assignment\n\nMasking: Double. Patients and investigators will be blinded to treatment assignments. Both intervention and placebo will be prepared and administered by trial nurse.\n\n\\- Study period\n\n24 months (Feb 2023-Feb 2025)\n\n\\-- Sample size\n\nAs this is a pilot study, a sample size of 16 patients in each arm will be taken.\n\n* Intervention\n* 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.\n* STATISTICAL ANALYSIS:\n* Primary outcome measure: Mann -Whitney U test\n* Secondary outcome measures\n\n * Fisher's exact test for categorical data\n * Mann-Whitney U test for continuous data\n* IBM® SPSS® Statistics 29 will be used for statistical analysis. P\\<0.05 will be considered as statistically significant.\n* Adverse effects\n* Stopping rule\n* 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.\n\n (c) Expected outcome of the project:\n\nThe 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."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '18 Years', 'minimumAge': '5 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Pediatric Acute Liver Failure as defined by PALF-Study Group\n\n * 5-18 years of age\n * INR \\> 2\n * Hepatic encephalopathy (defined by West Haven criteria)\n * Ammonia \\>100mcg/dL\n\nExclusion Criteria:\n\n* Irreversible neurological injury\n* Previous treatment with LOLA within 48 hours before admission.\n* Acute kidney injury.\n* Acute on chronic liver failure\n* Those not giving consent'}, 'identificationModule': {'nctId': 'NCT05778461', 'briefTitle': '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.', 'organization': {'class': 'OTHER', 'fullName': 'Institute of Liver and Biliary Sciences, India'}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'ILBS-ALF-06'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'L-ornithine L-Aspartate', 'description': '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.', 'interventionNames': ['Drug: L-ornithine L-Aspartate']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Placebo will be administered via continuous infusion for 72h, along with HVPE (2x plasma volume) starting at 8h, 32h and 56h respectively.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'L-ornithine L-Aspartate', 'type': 'DRUG', 'description': '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.', 'armGroupLabels': ['L-ornithine L-Aspartate']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo will be administered via continuous infusion for 72h, along with HVPE (2x plasma volume) starting at 8h, 32h and 56h respectively.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '110070', 'city': 'New Delhi', 'country': 'India', 'contacts': [{'name': 'Tamoghna Biswas, MD', 'role': 'CONTACT', 'email': 'tamoghnab@gmail.com', 'phone': '7439983747'}, {'name': 'Bikrant Bihari Lal, DM', 'role': 'CONTACT', 'email': 'bikrant18may@gmail.com', 'phone': '9540951063'}], 'facility': 'Institute of Liver and Biliary Sciences', 'geoPoint': {'lat': 28.62137, 'lon': 77.2148}}], 'centralContacts': [{'name': 'Dr Tamoghna Biswas, MD', 'role': 'CONTACT', 'email': 'tamoghnab@gmail.com', 'phone': '7439983747'}, {'name': 'Dr Bikrant Bihari Lal, DM', 'role': 'CONTACT', 'email': 'bikrant18may@gmail.com', 'phone': '9540951063'}], 'overallOfficials': [{'name': 'Dr Tamoghna Biswas, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Institute of Liver and Biliary Sciences'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Institute of Liver and Biliary Sciences, India', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}