Efficacy and Safety of Citrate Anticoagulation in CRRT for Patients With Liver Failure/DysfuncTION, the CAUTION Trial! A Retrospective Study on Etiology of Liver Failure and Their Complications (Caution)

Study design A retrospective cohort study will be conducted to compare the efficacy and safety of citrate anticoagulation in CRRT among patients with liver failure/dysfunction and severe shock.

Objectives

1. Primary Objective: To determine if the etiology of liver failure impacts the incidence of citrate-related complications in patients undergoing CRRT.
2. Secondary Objectives: To compare the efficacy of citrate anticoagulation in terms of renal recovery, filter lifespan, and patient survival between those with liver failure/dysfunction and severe shock.

Study Overview

• Status: Recruiting
• Conditions: Liver Failure; AKI - Acute Kidney Injury

Detailed Description

Continuous renal replacement therapy (CRRT) is a crucial intervention for managing acute kidney injury (AKI) in critically ill patients. Citrate anticoagulation has become a preferred method in CRRT due to its effect in longer filter longevity and less bleeding compared to unfractionated heparin1. However, its use in specific patient populations, such as those with liver failure or severe shock, necessitates careful evaluation.

Citrate acts as an anticoagulant by chelating calcium, an essential cofactor in the coagulation cascade, thus preventing clot formation within the extracorporeal circuit2. The citrate-calcium complex is then metabolized mainly in the liver, where citrate is converted into bicarbonate, and calcium is released back into the bloodstream. This mechanism provides dual benefits: effective anticoagulation and metabolic alkalization.

Patients with liver failure present unique challenges for citrate anticoagulation. Impaired liver function can lead to the accumulation of citrate, resulting in high anion gap metabolic acidosis and hypocalcemia3. These risks underscore the need for vigilant monitoring and potential adjustment of citrate dosing in this population. The aim of the present study is to explore whether the etiology of liver failure, which can range from alcoholic liver disease to drug-induced liver injury or shock liver, influences the incidence and severity of citrate-related complications.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Rita Jacobs, Dr.; Phone Number: +32 3 821 36 35; Email: rita.jacobs2@uza.be
• Study Contact Backup: Name: Petra Vertongen; Phone Number: +32 3 8214404; Email: studies.inzo@uza.be

Study Locations

• Belgium
  • Antwerp
    • Edegem, Antwerp, Belgium, 2650
      • Recruiting
      • Antwerp University Hospital
      • Contact: Rita Jacobs, Dr.; Phone Number: +32 3 821 36 35; Email: rita.jacobs2@uza.be
      • Contact: Petra Vertongen; Phone Number: +32 3 8214404; Email: studies.inzo@uza.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Critically ill patients diagnosed with AKI requiring CRRT

Description

Inclusion Criteria:

• Critically ill patients diagnosed with AKI requiring CRRT. Caution Protocol V1.0 24-07-2024
• Documented liver failure or significant liver dysfunction (e.g., elevated liver enzymes, bilirubin levels, or clinical diagnosis of liver failure) and clincal diagnosis of shock (NE of 0.25 μg/kg/min and or association of second vasopressor).
• Age ≥ 18 years.

Exclusion Criteria:

• NA

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Endpoint:	Incidence of citrate-related metabolic complications (e.g., citrate accumulation).	During admission at ICU

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Safety Endpoints	Incidence of electrolyte imbalances (e.g., hypocalcemia).; Incidence of adverse events related to anticoagulation.	During admission at ICU

Collaborators and Investigators

• Sponsor: University Hospital, Antwerp
• Investigators: Principal Investigator: Rita Jacobs, Dr., Antwerp Univesity Hospital

Publications and helpful links

General Publications

• Kramer L, Bauer E, Joukhadar C, Strobl W, Gendo A, Madl C, Gangl A. Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients. Crit Care Med. 2003 Oct;31(10):2450-5. doi: 10.1097/01.CCM.0000084871.76568.E6.
• Jacobs R, Verbrugghe W, Dams K, Roelant E, Couttenye MM, Devroey D, Jorens P. Regional Citrate Anticoagulation in Continuous Renal Replacement Therapy: Is Metabolic Fear the Enemy of Logic? A Systematic Review and Meta-Analysis of Randomised Controlled Trials. Life (Basel). 2023 May 17;13(5):1198. doi: 10.3390/life13051198.
• Mehta RL, McDonald BR, Aguilar MM, Ward DM. Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int. 1990 Nov;38(5):976-81. doi: 10.1038/ki.1990.300. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: April 2, 2025
• First Posted (Actual): April 3, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: April 2, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: liver failure; AKI; CRRT
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Digestive System Diseases; Liver Diseases; Renal Insufficiency; Acute Kidney Injury; Liver Failure; Hepatic Insufficiency
• Other Study ID Numbers: Project ID 6806; Edge 003873 (Other Identifier: Antwerp University Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No