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

Not Applicable

Recruiting

• Conditions: Acute on Chronic Liver Failure; Multiple Organ Failure
• Interventions: Device: MEX-CD1 Dialysis

• Registration Number: NCT06340269
• Lead Sponsor: Mexbrain

Brief Summary

The goal of this clinical trial is to test the MEX-CD1 hemodialysis medical device in patients suffering from ACLF. The main questions it aims to answer are:

* Is the device safe when used according to the instructions for use?

* Does the device work as expected by removing the excess of free iron from the blood?

Patients will receive 3 MEX-CD1 Slow Low volume CVVHD within 1 week.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2024-03-25
• Study First Submitted QC: 2024-03-25
• Study First Posted: 2024-04-01
• Study Start: 2024-06-21
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-19
• Last Update Posted: 2024-08-21
• Primary Completion: 2025-03
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MEX-CD1 Slow Low volume CVVHD	MEX-CD1 Dialysis	Patients enrolled in the treatment arm will receive 3 sessions of MEX-CD1 treatment in addition to standard of care

Primary Outcome Measures

Name	Time	Method
SADE for Safety purpose	From the enrollment until the last visit, assessed up to 7 days.	The safety will be assessed by percentage of subjects who discontinued MexACLF due to a serious adverse device event (SADE) between Day 1 and Day 7.

Secondary Outcome Measures

Name	Time	Method
hospital discharge	Between the screening visit and the last visit, assessed up to 28 days.	Length of stay at hospital
Mortality	Between the screening visit and the last visit, assessed up to 28 days.	Assessment of the survival rate
Performance of MEX-CD1	3 hours and 20 minutes; from treatment start (0 hours) to treatment end (3h20)	The performance of the MEX-CD1 slow low-volume CVVHD treatment in terms of iron extraction will be measured by the amount of iron extracted in the dialysate bags per treatment.
Change in Acute on Chronic Liver Failure (ACLF) Grade	Between the screening visit and the last visit, assessed up to 7 days.	Assessment of the change in ACLF Grade between the baseline and the end of study Min value = 0 (no ACLF) Max value=3b (Worse outcome)
Change in CLIF-C ACLF score	Between the screening visit and the last visit, assessed up to 7 days.	Assessment of the change in Chronic Liver Failure-Consortium (CLIF-C) ACLF score between the baseline and the end of study. CLIF-C ACLF = 10 × (0.33 × CLIF-C OFs + 0.04 x Age + 0.63 × ln (WBC count)-2); CLIF-OFs= Chronic Liver Failure Consortium Organe Failure Min value=6 (No organe Failure) Max value=18 (6 organe failures)
Improvement in individual organ function	Between the screening visit and the last visit, assessed up to 7 days.	Assessment of the change in individual organ function by using the CLIF sequential OF score; From 1 (no organe failure) to 3 (worse outcome) for the 6 organes below: Liver ; kidney ; Brain ; Coagulation ; Circulation ; Respiratory
Status of ICU	Between the screening visit and the last visit, assessed up to 28 days.	Length of stay in ICU
SAE for Safety purpose	From the start of the first MEX-CD1 treatment until the last visit, assessed up to 7 days.	The safety will be assessed by the percentage of patients who experience at least one related Serious Adverse Event (SAE) between Day 1 and Day 7.
Development of secondary infection	Between the screening visit and the last visit, assessed up to 7 days.	Assessment of development of secondary infection by need for new antibiotic therapy

Trial Locations

Locations (1)

Hôpital Croix Rousse, Service d'hépatologie et gastroentérologie; 🇫🇷 Lyon, Rhône-Alpes, France