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

Primary Purpose

Acute-On-Chronic Liver Failure, Anticoagulant Adverse Reaction, Sarcopenia

Status
Not yet recruiting
Phase
Not Applicable
Locations
Belgium
Study Type
Interventional
Intervention
CytoSorb
Sponsored by
University Hospital, Antwerp
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute-On-Chronic Liver Failure focused on measuring acute on chronic liver failure, sarcopenia, citrate anticoagulation, low molecular weight heparins, hand grip strength, skeletal muscle ultrasound, hemoadsorption, CRRT

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UZA

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

CytoSorb hemoadsorption

Control group

Arm Description

Patients with acute on chronic liver failure will receive CytoSorb treatment for 72 hours. The aim is to remove the molecules that drive systemic inflammation.

Historical group that received only standard medical care

Outcomes

Primary Outcome Measures

The impact of CytoSorb on serum bilirubin removal
20 participants with a serum bilirubin of ≥ 10 mg/dl will undergo CytoSorb for 72 hours
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)

Secondary Outcome Measures

changes in hemodynamic profile
Change in hemodynamic profile (i.e. mean arterial pressure normalized to norepinephrine equivalents) during the 72-h study intervention.
Vasopressors
Duration of vasopressor support in days
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
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.
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
Ventilation
Duration of mechanical ventilation,
Cytokines
Changes in cytokines (IL-6, IL-8, IL-16, TNF (tumor necrosis factor)-alpha) value (pg/ml)
Mortality
Mortality at 28, 60 and 90 days after enrolment
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
Cytosorb filter
Adverse events attributable to CytoSorb up to 28 days after enrolment
Change in Bile acids
Bile acids after 72 hours
Sarcopenia
Prevalence and development of sarcopenia
Anticoagulation
Adverse events attributable to anticoagulation
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
Change in inflammatory values: lactate
measurement of lactate (reference < 2 mmol/L)
Change in inflammatory values: procalcitonin
measurement of procalcitonin (reference < 0.5 ng/mL)

Full Information

First Posted
July 26, 2023
Last Updated
October 9, 2023
Sponsor
University Hospital, Antwerp
Collaborators
CytoSorbents Europe GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT06079021
Brief Title
COOLEY- Study: aCute On chrOnic Liver failurE Using the cYtosorb Device
Acronym
COOLEY
Official Title
COOLEY- Study: aCute On chrOnic Liver failurE Using the cYtosorb Device
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital, Antwerp
Collaborators
CytoSorbents Europe GmbH

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Application of CytoSorb treatment to ACLF patients
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CytoSorb hemoadsorption
Arm Type
Active Comparator
Arm Description
Patients with acute on chronic liver failure will receive CytoSorb treatment for 72 hours. The aim is to remove the molecules that drive systemic inflammation.
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Historical group that received only standard medical care
Intervention Type
Device
Intervention Name(s)
CytoSorb
Intervention Description
Application of CytoSorb treatment for 72 hours in patients with ACLF
Primary Outcome Measure Information:
Title
The impact of CytoSorb on serum bilirubin removal
Description
20 participants with a serum bilirubin of ≥ 10 mg/dl will undergo CytoSorb for 72 hours
Time Frame
24 and 72 hours
Title
Changes in ammonia and severity of hepatic encephalopathy during treatment period
Description
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)
Time Frame
24 and 72 hours
Secondary Outcome Measure Information:
Title
changes in hemodynamic profile
Description
Change in hemodynamic profile (i.e. mean arterial pressure normalized to norepinephrine equivalents) during the 72-h study intervention.
Time Frame
24 and 72 hours
Title
Vasopressors
Description
Duration of vasopressor support in days
Time Frame
24 and 72 hours
Title
ACLF (Acute on Chronic Liver Failure) Grading
Description
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
Time Frame
first week
Title
SOFA Score
Description
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.
Time Frame
0, 72 and 168 hours
Title
scores
Description
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
Time Frame
15 days
Title
Ventilation
Description
Duration of mechanical ventilation,
Time Frame
0, 24 and 72 hours
Title
Cytokines
Description
Changes in cytokines (IL-6, IL-8, IL-16, TNF (tumor necrosis factor)-alpha) value (pg/ml)
Time Frame
0, 24 and 72 hours
Title
Mortality
Description
Mortality at 28, 60 and 90 days after enrolment
Time Frame
28, 60 and 90 days after enrolment
Title
Improvement of Renal function after application of CytoSorb
Description
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
Time Frame
7, 14, 21 and 90 days after enrolment
Title
Cytosorb filter
Description
Adverse events attributable to CytoSorb up to 28 days after enrolment
Time Frame
up to 28 days after enrolment
Title
Change in Bile acids
Description
Bile acids after 72 hours
Time Frame
72 hours after enrolment
Title
Sarcopenia
Description
Prevalence and development of sarcopenia
Time Frame
0, 24 and 72 hours
Title
Anticoagulation
Description
Adverse events attributable to anticoagulation
Time Frame
0, 24 and 72 hours
Title
SAPS II score
Description
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
Time Frame
Day 0, Day 3, Day 7
Title
Change in inflammatory values: lactate
Description
measurement of lactate (reference < 2 mmol/L)
Time Frame
Day 0, Day 1 and Day 3
Title
Change in inflammatory values: procalcitonin
Description
measurement of procalcitonin (reference < 0.5 ng/mL)
Time Frame
Day 0, Day 1 and Day 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karolien Dams
Phone
+3238215175
Email
Karolien.Dams@uza.be
First Name & Middle Initial & Last Name or Official Title & Degree
Rita Jacobs
Phone
+3238214795
Email
rita.jacobs2@uza.be
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karolien Dams
Organizational Affiliation
University Hospital, Antwerp
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZA
City
Edegem
State/Province
Antwerp
ZIP/Postal Code
2650
Country
Belgium
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karolien Dams, MD
Phone
+3238215175
Email
Karolien.Dams@uza.be
First Name & Middle Initial & Last Name & Degree
Rita Jacobs, MD
Phone
+3238214795
Email
rita.jacobs2@uza.be

12. IPD Sharing Statement

Citations:
PubMed Identifier
22429562
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.
Results Reference
result
PubMed Identifier
36983259
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.
Results Reference
result
PubMed Identifier
31936597
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.
Results Reference
result
PubMed Identifier
28389120
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.
Results Reference
result
PubMed Identifier
37240843
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.
Results Reference
result

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

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