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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

• The impact of CytoSorb on serum bilirubin removal [Срок оценки: 24 and 72 hours]
• Changes in ammonia and severity of hepatic encephalopathy during treatment period [Срок оценки: 24 and 72 hours]

Вторичные конечные точки (12)

• changes in hemodynamic profile [Срок оценки: 24 and 72 hours]
• Vasopressors [Срок оценки: 24 and 72 hours]
• ACLF (Acute on Chronic Liver Failure) Grading [Срок оценки: first week]
• SOFA Score [Срок оценки: 0, 72 and 168 hours]
• scores [Срок оценки: 15 days]
• Ventilation [Срок оценки: 0, 24 and 72 hours]
• Cytokines [Срок оценки: 0, 24 and 72 hours]
• Mortality [Срок оценки: 28, 60 and 90 days after enrolment]
• Improvement of Renal function after application of CytoSorb [Срок оценки: 7, 14, 21 and 90 days after enrolment]
• Cytosorb filter [Срок оценки: up to 28 days after enrolment]
• Change in Bile acids [Срок оценки: 72 hours after enrolment]
• Sarcopenia [Срок оценки: 0, 24 and 72 hours]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• • 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бельгия · 1 центр

• UZA — Edegem

Публикации

• 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. PMID 22429562
• 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. PMID 36983259
• 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. PMID 31936597
• 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. PMID 28389120
• 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. PMID 37240843

Идентификаторы

NCT: NCT06079021 · Edge 2930

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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