A Novel Extracorporeal Liver Support Therapy In ALCF and to Evaluate the Efficacy of DIALIVE 2.0, a Liver Dialysis Device.

Ki vehet részt

• Adults aged 18-70 years, with a diagnosis of ACLF grade 2-4 (according to A-TANGO ACLF criteria, APPENDIX 1)
• ACLF non-responsive to SoC for up to 48 hours prior to developing grade 2-4 ACLF
• Inclusion within 10 days from the onset of A-TANGO ACLF grade ≥ 2

Ki nem vehet részt

• A-TANGO ACLF grade ≥2 for more than 10 days prior to inclusion
• Previous liver transplant
• Persistent haemodynamic instability as defined by:; (i) Norepinephrine(NE) dose >0.5µg/kg/min, or, (ii) If a second pressor is used, a composite Norepinephrine equivalence index (NEEI) of dose >0.5µg/kg/min (iii) Arterial lactate level >4mmol/L despite 24 hours of adequate fluid resuscitation and pressor therapy
• Established on renal replacement therapy for longer than 24 hours prior to inclusion
• Active or prior history of non hepatic malignancy unless adequately treated or in complete remission for five or more years
• Any participant who has received an investigational drug or device within 30 days, or who is scheduled to receive another investigational drug or device during the course of the study (concomitant observational studies are allowed)
• Invasive fungal infection (clinical or radiological evidence, not solely biomarker positivity such as BDG or galactomannan)
• Acute or sub-acute liver failure in the absence of cirrhosis
• Post-hepatectomy liver failure or primary non-function following transplantation
• Severe respiratory failure: PaO2/FiO2 (P/F) ≤ 200 mmHg or 27kPa
• Significant and/or uncontrolled bleeding (participants can be enrolled 48 hours after bleeding is controlled)
• Acute, extensive, portal vein thrombosis extending to and occluding superior mesenteric vein
• Major systemic illness, aside from liver disease, that in the opinion of the investigator would preclude the participant from participating in the study (e.g. coronary artery disease, cerebrovascular disease, chronic pulmonary disease, chronic kidney disease, serious psychiatric disease)
• Uncontrolled seizures
• Evidence of new intracranial pathology such as cerebral hemorrhage or infarction
• Participants diagnosed with Creutzfeldt-Jakob disease
• Known allergy to heparin, or type II thrombocytopaenia caused by heparin (HIT syndrome type II)
• Co-infection with HIV and AIDS defining illness i.e. CD4+ T-cell count below 200 cells/µL, a CD4+ T-cell percentage of total lymphocytes of less than 15%, or one of the defining illnesses such as PCP, Kaposi's sarcoma, CMV, Candidiasis etc
• Bacterial infection or sepsis unresponsive to treatment with antimicrobials for 48 hours indicated by (a) persistent pyrexia (b) rising white cell count, creactive protein and lactate (c) persistently positive cultures for bacteria or fungi and/or (d) worsening clinical state indicated by escalating requirement for fluid resuscitation, increasing vasopressors requirements or increasing organ support
• Severe thrombocytopaenia (absolute platelet count <20,000/mm3 at screening) or evidence of rapid decline in platelet count (> 50% reduction within the preceding 24 hrs)
• INR >3.0, unless sustained correction for >24 hours following FFP/PCC treatment
• Pre-existing chronic kidney disease (CKD) defined as eGFR (estimated glomerular filtration rate) <30 mL/min for 3 months or longer prior to screening
• Pregnancy
• Severe disseminated intravascular coagulopathy (DIC)
• A-TANGO WCC ACLF score >64 (APPENDIX 1)
• HCC outside of Milan criteria
• Severe frailty (Clinical Frailty Scale, CFS>5)
• Severe malnourishment (BMI<18)
• Participants not considered appropriate for full active treatment including organ support
• Participants who have a "do not attempt cardio-pulmonary resuscitation" order in place
• Participants unable to consent for themselves, unless a legal representative/consultee is appointed and approved as dictated by local and national legislation
• In the opinion of the investigator, recruitment to the the study would be unsafe for the participant