Continuous Renal Replacement Therapy Intensity in Hyperammonemia

NCT06987604 | Enrolling By Invitation

• 1 other identifier: 88020325.3.1001.5327
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Liver Failure; Acute on Chronic Liver Failure (ACLF); Acute Kidney Injury; Ammonia Metabolism

Keywords

ammonia; continuous renal replacement therapy; acute liver failure; acute on chronic liver failure; acute kidney injury

Outcome Measures

Primary Outcomes (1)

• Number of coma- and delirium-free days

  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).

  Day 1 to Day 28 post-randomization

Secondary Outcomes (7)

• Ammonia clearance at 12, 24, 48, and 72 hours

  Baseline to 72 hours

• Length of hospital stay

  Up to 90 days

• 28-day mortality

  28 days post randomization

• 90-day mortality

  90 days post-randomization

• Number of ventilator-free days within 28 days

  28 days post-randomization

Study Arms (2)

High-Dose CRRT

EXPERIMENTAL

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).

Device: High-dose continuous renal replacement therapy

Conventional-Dose CRRT

ACTIVE COMPARATOR

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).

Device: Conventional-dose continuous renal replacement therapy

Interventions

High-dose continuous renal replacement therapy DEVICE

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.

High-Dose CRRT

Conventional-dose continuous renal replacement therapy DEVICE

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.

Conventional-Dose CRRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• 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
• Indication for continuous renal replacement therapy (CRRT), as determined by the attending medical team
• Informed consent provided by the patient or legal representative

You may not qualify if:

• Age \< 18 years
• Pregnancy
• Diagnosis of acute liver failure (ALF) in the context of severe hemodynamic instability
• ALF secondary to ischemic hepatic injury

Sponsors & Collaborators

• Hospital de Clinicas de Porto Alegre: lead
• FIPE - Fundo de Incentivo a Pesquisa do Hospital de Clínicas de Porto Alegre: collaborator

Study Sites (1)

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90410-000, Brazil

Location

MeSH Terms

Conditions

Liver Failure, Acute; Acute-On-Chronic Liver Failure; Acute Kidney Injury

Interventions

Continuous Renal Replacement Therapy

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: 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.

Study Record Dates

• First Submitted: May 16, 2025
• First Posted: May 23, 2025
• Study Start: March 14, 2025
• Primary Completion (Estimated): May 14, 2029
• Study Completion (Estimated): May 14, 2029
• Last Updated: June 24, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

BR (1)