NCT07347275

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

A Multi-Centre, Randomised, Controlled Trial to Evaluate the Efficacy of DIALIVE 2.0, a Liver Dialysis Device, for the Treatment of Acute-on-Chronic Liver Failure (ACLF) A-TANGO Grade 2-4 Compared to Standard of Care (SoC)

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 72 (estimated)
• Sponsor: Yaqrit Ltd · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

DIALIVE 2.0 is an innovative liver dialysis device that specifically targets the underlying mechanisms of acute-on-chronic liver failure. The novelty of DIALIVE 2.0 lies in the combined use of a commercially available high cutoff filter and an extracorporeal endotoxin adsorber integrated into a hemofiltration and plasmapheresis platform. This allows controlled extracorporeal circulation of the participant's blood, during which the system removes dysfunctional, toxin-bound albumin and circulating endotoxins, while simultaneously replenishing functional albumin. The result is a comprehensive therapeutic approach that addresses both immune dysregulation and impaired albumin detoxification capacity in acute-on-chronic liver failure. This treatment concept is referred to as Selective Plasma filtration, Endotoxin Adsorption, and Albumin Replacement (SPEAR), reflecting the three core processes that underpin DIALIVE 2.0's mode of action. DIALIVE 2.0 is delivered as a daily treatment lasting six to eight hours, with a plasma filtration dose equivalent to 5% of the participant's ideal body weight. Albumin is replaced at a dose of one gram per kilogram of body weight using a 20% human albumin solution to offset albumin losses and maintain oncotic pressure. To address coagulation factor depletion observed in preclinical studies (see Investigators Brochure), one unit of fresh frozen plasma is administered at the end of each session to restore haemostatic balance. The DIALIVE 2.0 system includes the following components: * Medica FRACTIOsmart Small 1.0 haemodialyser with a high cut-off membrane (150 to 200 kilodaltons), used for the removal of albumin-bound toxins and medium-sized inflammatory molecules. This component is commercially available under European certification MDR 00048-A. * Alteco® Medical LPS Adsorber, an extracorporeal filter designed for the selective removal of circulating endotoxin in conditions where endotoxemia is suspected or confirmed. This is a commercially available device certified under CE 0402, (awaiting MHRA registration). * Medica AFERsmart Plus™ System, a plasmapheresis platform that controls flow rates, treatment duration, and pressure regulation. This is commercially available, and CE marked under number 0476. * Medica AFERsmart Standard TPE Line, a sterile, CE-marked disposable tubing set compatible with the AFERsmart Plus device. * Male to male tubing set, and absorber connector, (pending commercial approval).

Conditions

• Acute-on-Chronic Liver Failure (ACLF)
• Liver Cirrhosis

Interventions

Type	Name	Description
OTHER	Standard of Care (Investigator Choice)	Standard of care as per Investigator discretion
DEVICE	DIALIVE 2.0 liver dialysis Device plus available Standard of Care	DIALIVE 2.0 liver dialysis Device plus available Standard of Care

Timeline

• Start date: 2026-05-01
• Primary completion: 2027-03-01
• Completion: 2027-05-01
• First posted: 2026-01-16
• Last updated: 2026-04-14