COOLEY- Study: aCute On chrOnic Liver failurE Using the cYtosorb Device

Sarcopenia Clinical Trial

— COOLEY  

Official title:

COOLEY- Study: aCute On chrOnic Liver failurE Using the cYtosorb Device

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06079021
• Other study ID #: Edge 2930
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2024
• Est. completion date: June 30, 2027

Study information

• Verified date: May 2024
• Source: University Hospital, Antwerp
• Contact: Karolien Dams
• Phone: +3238215175
• Email: Karolien.Dams[@]uza.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: June 30, 2027
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• Anticoagulant Adverse Reaction
• End Stage Liver Disease
• Hepatic Insufficiency
• Liver Failure
• Sarcopenia
• Ultrasonography

Intervention

Device:
• CytoSorb
Application of CytoSorb treatment for 72 hours in patients with ACLF

Locations

Country	Name	City	State
Belgium	UZA	Edegem	Antwerp

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Antwerp	CytoSorbents Europe GmbH

Country where clinical trial is conducted

Belgium, 

References & Publications (5)

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. — View 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 Tr — View 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 M — View 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. — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The impact of CytoSorb on serum bilirubin removal	20 participants with a serum bilirubin of = 10 mg/dl will undergo CytoSorb for 72 hours	24 and 72 hours
Primary	Changes in ammonia and severity of hepatic encephalopathy during treatment period	The West Haven criteria are used for grading the severity of hepatic encephalopathy, which include 5 grades ranging from minimal (slightly impaired) to grade IV (comatose)	24 and 72 hours
Secondary	changes in hemodynamic profile	Change in hemodynamic profile (i.e. mean arterial pressure normalized to norepinephrine equivalents) during the 72-h study intervention.	24 and 72 hours
Secondary	Vasopressors	Duration of vasopressor support in days	24 and 72 hours
Secondary	ACLF (Acute on Chronic Liver Failure) Grading	Assessment of ACLF grading (minimum 0 - maximum 3; higher score means a worse outcome) during the 72h intervention up to 1 week after diagnosis of ACLF	first week
Secondary	SOFA Score	Changes in Sequential Organ Failure Assessment (SOFA) (minimum 0-maximum 24; higher score means a worse outcome) score during the 72h study period and up to 1 week after.	0, 72 and 168 hours
Secondary	scores	Changes in CLIF-C (Chronic Liver Failure Consortium)(minimu 0 - maximum 100; higher score means a worse outcome) score during the 72-h intervention, up to 15 days after diagnosis of ACLF	15 days
Secondary	Ventilation	Duration of mechanical ventilation,	0, 24 and 72 hours
Secondary	Cytokines	Changes in cytokines (IL-6, IL-8, IL-16, TNF (tumor necrosis factor)-alpha) value (pg/ml)	0, 24 and 72 hours
Secondary	Mortality	Mortality at 28, 60 and 90 days after enrolment	28, 60 and 90 days after enrolment
Secondary	Improvement of Renal function after application of CytoSorb	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) will receive CytoSorb treatmetn. Serum creatinine will be measured at day 7, 14, 21 and 90 days	7, 14, 21 and 90 days after enrolment
Secondary	Cytosorb filter	Adverse events attributable to CytoSorb up to 28 days after enrolment	up to 28 days after enrolment
Secondary	Change in Bile acids	Bile acids after 72 hours	72 hours after enrolment
Secondary	Sarcopenia	Prevalence and development of sarcopenia	0, 24 and 72 hours
Secondary	Anticoagulation	Adverse events attributable to anticoagulation	0, 24 and 72 hours
Secondary	SAPS II score	Simplified Acute Physiology Score II (SAPS II) (minimum 0 - maximum 163; higher score means a worse outcome) during the 72-h study intervention and up to 1 week after	Day 0, Day 3, Day 7
Secondary	Change in inflammatory values: lactate	measurement of lactate (reference < 2 mmol/L)	Day 0, Day 1 and Day 3
Secondary	Change in inflammatory values: procalcitonin	measurement of procalcitonin (reference < 0.5 ng/mL)	Day 0, Day 1 and Day 3