Clinical trial NCT06079021: COOLEY- Study: ACute on ChrOnic Liver FailurE Using the CYtosorb Device
Official title: COOLEY- Study: ACute on ChrOnic Liver FailurE Using the CYtosorb Device
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute-On-Chronic Liver Failure
Anticoagulant Adverse Reaction
Sarcopenia
Ultrasonography
Keywords: acute on chronic liver failure
sarcopenia
citrate anticoagulation
low molecular weight heparins
hand grip strength
skeletal muscle ultrasound
hemoadsorption
CRRT
Lead sponsor: University Hospital, Antwerp
Sponsor class: OTHER
Collaborators: name: CytoSorbents Europe GmbH
First posted: 2023-10-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Application of CytoSorb treatment to ACLF patients
Primary purpose: TREATMENT

Brief summary: A Prospective, Single-Center trial, in Patients With Acute on Chronic Liver Failure. Study of Standard Medical Care Plus CytoSorb® Compared to Standard Medical Care Alone in a historical group.

Detailed description: The study team wants to investigate the effect of Cytosorb hemoadsorption on the bilirubin level as well as on the ammonia level changes induced by the therapy in patients with Acute on Chronic Liver Failure (ACLF) .

In this group of patients with ACLF grade 2 and 3 the investigators want to determine the prevalence and development of sarcopenia by sequential quadriceps and thenar ultrasound images and by handgrip strength measurement.

The investigators will objectify muscle mass by skeletal muscle ultrasound of quadriceps and thenar muscles in this sickest subgroup of cirrhotic patients. Ultrasound forms a part of the daily clinical routine in ICU. The study team wants to compare both measurements and objectify the evolution to study the reliability and validity of ultrasound to quantify muscles in chronic liver disease and its clinical values. Most of ultrasonographic studies are based on quadriceps exploration, which is more inconvenient and takes more time than exploring the hands because patients need to remove clothes and lie down. The study team also hypothesizes that thenar muscles are less subject to fluid overload than the quadriceps muscles are.

When available, lumbar skeletal muscle indices will be compared by computed tomography or magnetic resonance imaging.

In this group of patients with ACLF, receiving Continuous Renal Replacement Therapy (CRRT) the appropriate choice of anticoagulant remains controversial. The objective of this study is to compare the efficacy and safety of regional citrate anticoagulation (RCA) and Low Molecular Weight Heparin (LMWH) in critically ill ACLF patients requiring CRRT. These two commercially available anticoagulation methods are used in daily practice in the ICU. The first 10 patients will receive anticoagulation with LMWH with monitoring of anti-Xa. The second cohort of patients will receive RCA.

Eligibility criteria: Inclusion Criteria:

* adult patients (≥ 18 years) admitted to the University Hospital of Antwerp (UZA), Belgium.

  * Written informed consent from patient or if not possible due to encephalopathy (\> grade 2): legal representative
  * acute-on-chronic liver failure (ACLF) grade ≥ 2:

    * Acute decompensation event (identifiable trigger)
    * Hepatic encephalopathy grade ≥ 2
    * Acute kidney injury (AKI) according to Kidney Disease: Improving Global Outcome (KDIGO) criteria stage 3 (≥ 3-fold increase of serum creatinine OR increase of serum creatinine to ≥ 4 mg/dl OR urine output ≤ 0.3 ml/kg/h for ≥ 24 hours OR anuria for ≥ 12 hours)
    * Serum bilirubin ≥ 10 mg/dl
    * Hemodynamic instability with vasopressor support (norepinephrine \> 0.05 mcg/kg/min)

Exclusion Criteria:

* • known patient will against participation in the study or against the measures applied in the study

  * a decision made prior to inclusion to stop further treatment of the patient within the next 24 hours
  * no complete remission of malignancy including hepatocellular carcinoma within the past 12 months
  * ongoing intermittent or CRRT before study inclusion

Primary outcomes:
measure: The impact of CytoSorb on serum bilirubin removal
timeFrame: 24 and 72 hours
measure: Changes in ammonia and severity of hepatic encephalopathy during treatment period
timeFrame: 24 and 72 hours
Secondary outcomes:
measure: changes in hemodynamic profile
timeFrame: 24 and 72 hours
measure: Vasopressors
timeFrame: 24 and 72 hours
measure: ACLF (Acute on Chronic Liver Failure) Grading
timeFrame: first week
measure: SOFA Score
timeFrame: 0, 72 and 168 hours
measure: scores
timeFrame: 15 days
measure: Ventilation
timeFrame: 0, 24 and 72 hours
measure: Cytokines
timeFrame: 0, 24 and 72 hours
measure: Mortality
timeFrame: 28, 60 and 90 days after enrolment
measure: Improvement of Renal function after application of CytoSorb
timeFrame: 7, 14, 21 and 90 days after enrolment
measure: Cytosorb filter
timeFrame: up to 28 days after enrolment
measure: Change in Bile acids
timeFrame: 72 hours after enrolment
measure: Sarcopenia
timeFrame: 0, 24 and 72 hours
measure: Anticoagulation
timeFrame: 0, 24 and 72 hours
measure: SAPS II score
timeFrame: Day 0, Day 3, Day 7
measure: Change in inflammatory values: lactate
timeFrame: Day 0, Day 1 and Day 3
measure: Change in inflammatory values: procalcitonin
timeFrame: Day 0, Day 1 and Day 3
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: UZA
state: Antwerp
Study officials:
affiliation: University Hospital, Antwerp
name: Karolien Dams
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wlodzimirow KA, Eslami S, Abu-Hanna A, Nieuwoudt M, Chamuleau RA. A systematic review on prognostic indicators of acute on chronic liver failure and their predictive value for mortality. Liver Int. 2013 Jan;33(1):40-52. doi: 10.1111/j.1478-3231.2012.02790.x. Epub 2012 Mar 19.
citation: Popescu M, David C, Marcu A, Olita MR, Mihaila M, Tomescu D. Artificial Liver Support with CytoSorb and MARS in Liver Failure: A Retrospective Propensity Matched Analysis. J Clin Med. 2023 Mar 14;12(6):2258. doi: 10.3390/jcm12062258.
citation: Buchard B, Boirie Y, Cassagnes L, Lamblin G, Coilly A, Abergel A. Assessment of Malnutrition, Sarcopenia and Frailty in Patients with Cirrhosis: Which Tools Should We Use in Clinical Practice? Nutrients. 2020 Jan 9;12(1):186. doi: 10.3390/nu12010186.
citation: Lopes J, Grams ST, da Silva EF, de Medeiros LA, de Brito CMM, Yamaguti WP. Reference equations for handgrip strength: Normative values in young adult and middle-aged subjects. Clin Nutr. 2018 Jun;37(3):914-918. doi: 10.1016/j.clnu.2017.03.018. Epub 2017 Mar 24.
citation: 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.