Ignite Creation Date:
2025-12-24 @ 9:12 PM
Ignite Modification Date:
2025-12-31 @ 11:19 PM
Study NCT ID:
NCT06987604
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2025-06-24
First Post:
2025-05-16
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Continuous Renal Replacement Therapy Intensity in Hyperammonemia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D017114', 'term': 'Liver Failure, Acute'}, {'id': 'D065290', 'term': 'Acute-On-Chronic Liver Failure'}, {'id': 'D058186', 'term': 'Acute Kidney Injury'}], 'ancestors': [{'id': 'D017093', 'term': 'Liver Failure'}, {'id': 'D048550', 'term': 'Hepatic Insufficiency'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D051437', 'term': 'Renal Insufficiency'}, {'id': 'D007674', 'term': 'Kidney Diseases'}, {'id': 'D014570', 'term': 'Urologic Diseases'}, {'id': 'D052776', 'term': 'Female Urogenital Diseases'}, {'id': 'D005261', 'term': 'Female Urogenital Diseases and Pregnancy Complications'}, {'id': 'D000091642', 'term': 'Urogenital Diseases'}, {'id': 'D052801', 'term': 'Male Urogenital Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000079664', 'term': 'Continuous Renal Replacement Therapy'}], 'ancestors': [{'id': 'D017582', 'term': 'Renal Replacement Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D005112', 'term': 'Extracorporeal Circulation'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'OUTCOMES_ASSESSOR'], 'maskingDescription': 'Outcome assessors will be blinded to the treatment allocation. Clinical staff and investigators responsible for administering the intervention will not be blinded due to the nature of the dialysis prescription. However, standardized data collection protocols and blinded outcome adjudication will be employed to minimize bias.'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants will be randomly assigned in a 1:1 ratio to receive either conventional-dose (25-35 mL/kg/h) or high-dose (45-55 mL/kg/h) continuous renal replacement therapy. Each participant will remain in their assigned treatment arm throughout the study period.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 152}}, 'statusModule': {'overallStatus': 'ENROLLING_BY_INVITATION', 'startDateStruct': {'date': '2025-03-14', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-05', 'completionDateStruct': {'date': '2029-05-14', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-06-18', 'studyFirstSubmitDate': '2025-05-16', 'studyFirstSubmitQcDate': '2025-05-16', 'lastUpdatePostDateStruct': {'date': '2025-06-24', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-05-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2029-05-14', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Number of coma- and delirium-free days', 'timeFrame': 'Day 1 to Day 28 post-randomization', 'description': 'The number of days during the first 28 days after randomization in which the patient is alive and free of coma or delirium, assessed using standardized neurological evaluation tools such as the Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Method for the ICU (CAM-ICU).'}], 'secondaryOutcomes': [{'measure': 'Ammonia clearance at 12, 24, 48, and 72 hours', 'timeFrame': 'Baseline to 72 hours', 'description': 'Serial arterial ammonia levels will be measured to calculate the reduction in ammonia concentration from baseline at 12, 24, 48, and 72 hours after initiation of CRRT.'}, {'measure': 'Length of hospital stay', 'timeFrame': 'Up to 90 days', 'description': 'Total number of days from hospital admission to discharge'}, {'measure': '28-day mortality', 'timeFrame': '28 days post randomization', 'description': 'All-cause mortality within 28 days after randomization'}, {'measure': '90-day mortality', 'timeFrame': '90 days post-randomization', 'description': 'All-cause mortality within 90 days after randomization.'}, {'measure': 'Number of ventilator-free days within 28 days', 'timeFrame': '28 days post-randomization', 'description': 'Number of days within the first 28 days post-randomization during which the patient is alive and not receiving invasive mechanical ventilation.'}, {'measure': 'Incidence of safety outcomes, such as hypophosphatemia, dialysis disequilibrium syndrome, and rapid correction of hyponatremia', 'timeFrame': 'From CRRT initiation up to 7 days or until therapy discontinuation', 'description': 'Adverse events will be monitored and recorded during CRRT, including laboratory-confirmed hypophosphatemia (phosphate \\<2.5 mg/dL), clinical signs of dialysis disequilibrium syndrome, and serum sodium correction \\>10 mmol/L in 24 hours.'}, {'measure': 'Improvement in cerebral compliance', 'timeFrame': 'Baseline to Day 28 post-randomization', 'description': 'Cerebral compliance will be assessed using the Brain4care noninvasive monitoring system. Improvement will be defined as normalization or favorable trend in intracranial compliance waveform patterns compared to baseline.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['ammonia', 'continuous renal replacement therapy', 'acute liver failure', 'acute on chronic liver failure', 'acute kidney injury'], 'conditions': ['Acute Liver Failure', 'Acute on Chronic Liver Failure (ACLF)', 'Acute Kidney Injury', 'Ammonia Metabolism']}, 'descriptionModule': {'briefSummary': 'Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are life-threatening conditions often associated with hyperammonemia, hepatic encephalopathy, and multi-organ dysfunction. Ammonia plays a central role in the pathogenesis of cerebral edema and neurotoxicity. Continuous renal replacement therapy (CRRT) has been shown to effectively reduce serum ammonia levels and may improve transplant-free survival in ALF. However, the optimal dialysis dose for ammonia clearance and neurological recovery remains uncertain. This randomized, multicenter clinical trial aims to compare conventional-dose (25-35 mL/kg/h) versus high-dose (45-55 mL/kg/h) CRRT in patients with ALF or ACLF and arterial ammonia \\>72 μmol/L. The primary outcome is the number of coma- and delirium-free days. Secondary outcomes include ammonia clearance and additional parameters of cerebral function monitoring.', 'detailedDescription': "Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) are critical conditions characterized by rapid deterioration in hepatic function, coagulopathy, hepatic encephalopathy, and multi-organ failure. Elevated serum ammonia levels are frequently observed in these patients and are strongly associated with cerebral dysfunction, including coma and delirium. Ammonia contributes to the development of brain edema through mechanisms involving astrocyte swelling, oxidative stress, and altered neurotransmission. Rapid and effective reduction of ammonia is a key therapeutic target in the management of these patients.\n\nContinuous renal replacement therapy (CRRT) is commonly used in critically ill patients with ALF or ACLF, particularly in those with hyperammonemia. While CRRT is effective in lowering ammonia levels, there is currently no consensus regarding the optimal dialysis dose to maximize ammonia clearance and improve neurological outcomes. Observational data and small interventional studies suggest a potential benefit of higher CRRT doses in terms of ammonia removal and clinical improvement, but robust evidence from randomized trials is lacking.\n\nThis study is a randomized, controlled, multicenter clinical trial designed to compare the effects of two different CRRT dosing strategies on cerebral function in patients with ALF or ACLF and arterial ammonia levels \\>72 μmol/L. Eligible patients will be randomized to receive either conventional-dose CRRT (25-35 mL/kg/h) or high-dose CRRT (45-55 mL/kg/h). All other aspects of clinical management will follow current standard-of-care protocols.\n\nThe primary endpoint is the number of coma- and delirium-free days during the intervention period. Secondary outcomes include the degree of ammonia clearance, time to normalization of ammonia levels, filter lifespan, need for rescue therapies (e.g., liver transplantation), mortality, and neurological function monitoring using noninvasive technologies. The study seeks to generate high-quality evidence to guide CRRT dosing decisions in the context of hyperammonemia due to liver failure.\n\nProtocol Amendment - Change in Stratification Ratio The original protocol assumed a balanced enrollment of patients with Acute Liver Failure (ALF) and Acute-on-Chronic Liver Failure (ACLF), with an intended 1:1 distribution across both strata. However, after initiating recruitment and observing actual prevalence patterns at participating centers, it became evident that the number of eligible patients with ACLF significantly exceeds that of ALF.\n\nIn response, the study protocol was amended to reflect a revised stratification ratio of 1:5 (ALF: ACLF). Within each stratum, randomization to treatment arms (conventional-dose vs. high-dose CRRT) remains 1:1.\n\nThis adjustment enhances recruitment feasibility and reflects the real-world distribution of liver failure phenotypes, without altering the study's scientific objectives, eligibility criteria, or outcome measures."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Age ≥ 18 years\n* Diagnosis of acute liver failure (ALF) or acute-on-chronic liver failure (ACLF) Presence of hyperammonemia, defined as: Arterial ammonia \\>72 μmol/L and hepatic encephalopathy grade ≥2 or Arterial ammonia \\>100 μmol/L regardless of encephalopathy grade\n* Indication for continuous renal replacement therapy (CRRT), as determined by the attending medical team\n* Informed consent provided by the patient or legal representative\n\nExclusion Criteria:\n\n* Age \\< 18 years\n* Pregnancy\n* Diagnosis of acute liver failure (ALF) in the context of severe hemodynamic instability\n* ALF secondary to ischemic hepatic injury'}, 'identificationModule': {'nctId': 'NCT06987604', 'acronym': 'CRITICAL', 'briefTitle': 'Continuous Renal Replacement Therapy Intensity in Hyperammonemia', 'organization': {'class': 'OTHER', 'fullName': 'Hospital de Clinicas de Porto Alegre'}, 'officialTitle': 'Continuous Renal Replacement Therapy Intensity in TreatIng Critical Ammonemia Levels', 'orgStudyIdInfo': {'id': '88020325.3.1001.5327'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'High-Dose CRRT', 'description': 'Participants in this group will receive continuous renal replacement therapy (CRRT) at a high effluent dose of 45-55 mL/kg/h for the treatment of hyperammonemia in the context of acute liver failure (ALF) or acute-on-chronic liver failure (ACLF).', 'interventionNames': ['Device: High-dose continuous renal replacement therapy']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Conventional-Dose CRRT', 'description': 'Participants in this group will receive continuous renal replacement therapy (CRRT) at a conventional effluent dose of 25-35 mL/kg/h for the treatment of hyperammonemia in the context of acute liver failure (ALF) or acute-on-chronic liver failure (ACLF).', 'interventionNames': ['Device: Conventional-dose continuous renal replacement therapy']}], 'interventions': [{'name': 'High-dose continuous renal replacement therapy', 'type': 'DEVICE', 'description': 'Continuous renal replacement therapy administered at an effluent dose of 45-55 mL/kg/h using standard equipment and protocols for critically ill patients with ALF or ACLF and hyperammonemia.', 'armGroupLabels': ['High-Dose CRRT']}, {'name': 'Conventional-dose continuous renal replacement therapy', 'type': 'DEVICE', 'description': 'Continuous renal replacement therapy administered at an effluent dose of 25-35 mL/kg/h using standard equipment and protocols for critically ill patients with ALF or ACLF and hyperammonemia.', 'armGroupLabels': ['Conventional-Dose CRRT']}]}, 'contactsLocationsModule': {'locations': [{'zip': '90410-000', 'city': 'Porto Alegre', 'state': 'Rio Grande do Sul', 'country': 'Brazil', 'facility': 'Hospital de Clinicas de Porto Alegre', 'geoPoint': {'lat': -30.03283, 'lon': -51.23019}}]}, 'ipdSharingStatementModule': {'ipdSharing': 'YES'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hospital de Clinicas de Porto Alegre', 'class': 'OTHER'}, 'collaborators': [{'name': 'FIPE - Fundo de Incentivo a Pesquisa do Hospital de Clínicas de Porto Alegre', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD', 'investigatorFullName': 'Gabriel Sartori Pacini', 'investigatorAffiliation': 'Hospital de Clinicas de Porto Alegre'}}}}