Clinical trials

This study is intended to demonstrate the efficacy and safety of the DIALIVE Liver Dialysis Device when incorporated into the standard management plan for participants with A-TANGO ACLF grade 2-4. A total of 72 evaluable participants, aged 18-70, will be enrolled in up to 12 clinical centres in the United Kingdom. Participants must have a history of liver cirrhosis and a deterioration within four weeks due to a precipitating event, leading to A-TANGO ACLF grade 2-4. Multicenter, individually randomised, controlled, open-label, parallel group trial using double-arm design. The control group will receive SoC for participants with ACLF. The DIALIVE 2.0 treatment group will receive SoC with the addition of up to 7 (seven) daily DIALIVE 2.0 treatment sessions within the 10-day treatment window. Seventy-two participants with ACLF (60% A-TANGO ACLF grade 2 at randomisation, and 40% A-TANGO ACLF grade 3 \& 4 at randomisation) will be randomised 1:1 to receive either SoC or SoC + DIALIVE 2.0. This allows for 5% loss due to drop-out, and 5% censoring due to liver transplantation within 28 days. All randomised participants will be included in the intention to treat (ITT) analysis while all participants that receive at least one treatment cycle will be used for the safety population. For each participant, the study duration will be up to 105 days (screening: 5 days; treatment up to 10 days; follow up 90 days). The total study duration is estimated to be approximately 18 months from screening of first participant until study completion of the last participant.

The purpose of this research is to know if a new combination of drugs (TAK-242 and G-CSF) in combination with standard therapy for acute-on-chronic liver failure (ACLF) is more effective than standard therapy for ACLF treatment and is safe. Description of the population to be studied: ACLF is a syndrome that occurs in patients with chronic liver disease, with or without previously diagnosed cirrhosis, which is characterized by acute hepatic decompensation. Cirrhosis is a chronic disease of the liver marked by degeneration of cells, inflammation, and thickening and scarring (fibrosis) of liver tissue. Hepatic decompensation is a sudden decline in liver function. It is characterized by severe liver damage and complications like jaundice (yellowing of the skin or whites of the eyes), ascites (a condition where excess fluid accumulates in the abdominal cavity and in abdominal organs) and encephalopathy (a group of symptoms that result from damage or dysfunction in the brain, causing a range of cognitive and neurological impairments). It may result in liver failure, one or more organ failures other than liver (renal, brain, coagulation, respiratory, cardiovascular), and is associated with increased mortality within 28-days and up to 3 months from onset. Grade 1 ACLF has a \>15% risk of mortality at 28 days. Purpose of the study: The investigational medication, TAK-242, is aimed at stopping an "over-reaction" of the immune system (the body's defense system) while G-CSF encourages your liver cells to grow. In patients with severe inflammation of the liver due to alcohol \[severe alcoholic hepatitis (sAH)\] and ACLF, this over-reaction may cause the liver and other organs in the body to suddenly stop working (organ failure). The hypothesis of the study is that by blocking this over-reaction and encouraging your liver cells to grow your condition may improve.