Feasibility Pilot Study to Evaluate the Safety and Performance of the MEX-CD1 Medical Device in ACLF

This study investigates the safety and performance of the MEX-CD1 slow low volume CVVHD device in patients suffering from ACLF.

Acute-on-chronic liver failure (ACLF) is defined as a syndrome in patients with acutely decompensated cirrhosis, associated with single or multiple organ failures, and characterized by a high short-term mortality. ACLF is frequently triggered by a precipitating event (alcoholic hepatitis, infection, gastrointestinal haemorrhage) and characterized by an intense systemic inflammatory response driven per pathogen-associated molecular patterns (PAMPs) and/or damage-associated molecular patterns (DAMPs) responsible of the development of organs failure through tissues hypoperfusion, immune-mediated tissue damages and mitochondrial dysfunction.

Very importantly, ACLF is a very dynamic syndrome that has potential for reversibility. It is hypothesized that the extraction of non-transferrin bound iron (NTBI) could break down the vicious cycle of the excessive inflammatory responses, reduce oxidative stress and inhibit pathogen proliferation in ACLF patients.

As a consequence, it is hypothesized that the extraction of NTBI could promote improvement of ACLF grade n to ACLF grade n-1 or no ACLF. It is hypothesized that the extraction of NTBI could stop the progression of ACLF by preventing further organ failures and by reducing bacterial infection. Thereby, the extraction of NTBI could restore the eligibility of ACLF patients to liver transplantation, and, with or without liver transplantation, allow an earlier discharge from intensive care and prolong survival.

The proposed medical device, by combining dialysis to a hyper-chelating colloidal dialysate (MEX-CD1), specifically extracts free iron from the blood.

All patients enrolled in this study will receive 3 MEX-CD1 Slow Low volume CVVHD within 1 week. The duration of each MEX-CD1 Slow Low volume CVVHD session is 3h20.

Inclusion criteria

• Male or female subjects ≥18 years and ≤80 years
• Subject is able to provide informed consent to participate in the study, otherwise written consent must be obtained on behalf of the subject by a next of kin or legal representative in accordance with local ethical and legal requirements
• History of an acute decompensation event (including but not limited to ascites, gastrointestinal bleeding, hepatic encephalopathy and/or acute bacterial infections), occurring within ≤6 weeks of screening
• Cirrhosis (diagnosed based on clinical, biological, morphological parameters or liver biopsy)
• Subject with:

• ACLF Grade 2, 3a or 3b based on the CLIF-C OF score
• Under continuous renal replacement therapy (CRRT) or any organ support device that requires catheter placement

Exclusion criteria

• Subjects with acute or sub-acute liver failure without an underlying cirrhosis
• Subjects not considered appropriate for full active treatment including organ support or those with a Do Not Attempt Cardio-Pulmonary Resuscitation order (DNACPR)
• Subjects who have received any investigational drug or device within 30 days of dosing or who are scheduled to receive another investigational drug or device in the course of the study; concomitant observational studies are allowed
• Evidence of uncontrolled seizures
• In females: known pregnancy or lactating
• Patients with a known allergy to shellfish
• Patients for who, in the opinion of the investigator, it would be unsafe to be considered for the study
• Vulnerable population according to Articles 64 to 68 of the Regulations (EU) 2017/745 on Medical Devices
• Patient with weight < 30 kg