Safety and Performance Trial of DIALIVE Liver Dialysis Device in Acute On Chronic Liver Failure Patients

NCT03065699 | Completed DMC

• 2 other identifiers: YAQ-002CIV-16-08-016644
• Study Type: interventional
• Target: 30
• Locations: 8 countries
• Sites: 12

Brief Summary

The First-In-Man study is a multi-centre, randomised, controlled, study to generate data for the evaluation of safety and performance of DIALIVE Liver Dialysis Device in 24 evaluable patients with Acute on Chronic Liver Failure (ACLF) versus standard of care (SOC).

Conditions

Acute on Chronic Liver Failure

Keywords

Medical device; Liver dialysis; Haemofilter; ACLF

Outcome Measures

Primary Outcomes (2)

• Safety of DIALIVE in terms of percentage of ACLF patients experiencing serious adverse events during DIALIVE treatment period.

  To evaluate the safety of the DIALIVE device in patients with Acute on Chronic Liver Failure Grades 1 and 2 (ACLF). Outcome measure is: The percentage of subjects who experience at least one (1) serious adverse event (SAE) between Day 1 and Day 10.(DIALIVE arm only). Outcome is measured on day 10 and compared between treatment arms.

  Treatment period is from 1 to 10 days post-randomization.

• Safety of DIALIVE in terms of percentage of ACLF patients who discontinued treatment due to severe adverse event.

  The outcome measure is the percentage of subjects who discontinued DIALIVE treatment due to a serious adverse device event (SADE) between Day 1 (first day of treatment) and Day 10.(DIALIVE arm only)

  Treatment period is from 1 to 10 days post-randomization.

Secondary Outcomes (9)

• Performance of DIALIVE by assessing removal of endotoxins.

  End of DIALIVE treatment (max 10 days after randomization)

• Performance of DIALIVE by assessing removal of albumin.

  End of DIALIVE treatment (max 10 days after randomization)

• Change in Clinical Parameters by DIALIVE treatment (ACLF grade and score) between treatment arms.

  Treatment period is from 1 to 10 days post-randomization

• Change in Clinical Parameters by DIALIVE treatment (ACLF grade) between treatment arms.

  Treatment period is from 1 to 10 days post-randomization

• Change in mortality between treatment arms.

  At day 28 post-randomization (for all patients). At day 90 for those patients enrolled under protocol version 6.0.

Other Outcomes (7)

• Efficacy of the DIALIVE for liver function: changes in MELD score

  Treatment period is from 1 to 10 days post-randomization

• Efficacy of the DIALIVE for kidney function: changes in creatine and NGAL

  Treatment period is from 1 to 10 days post-randomization

• Efficacy of the DIALIVE for brain function: changes in West Haven Criteria

  Treatment period is from 1 to 10 days post-randomization

Study Arms (2)

Standard of Care

NO INTERVENTION

For patients with ACLF grade 1 or 2 and randomised to the 'Standard of care' arm, the location of treatment (ICU or general ward) will be determined by their clinical need and will be decided by the site Principal Investigator. They will receive standard of care.

DIALIVE Liver Dialysis Device treatment arm

ACTIVE COMPARATOR

Patients with ACLF grade 1 and ACLF grade 2 on the background of alcoholic cirrhosis randomized to the DIALIVE arm will receive treatment in an intensive care (ICU) or renal dialysis unit setting. They will receive DIALIVE treatment according to a fixed treatment schedule over a period of 10 days post-randomization.

Device: DIALIVE Liver Dialysis Device

Interventions

DIALIVE Liver Dialysis Device DEVICE

ACLF patients will receive dialysis treatment for 8-12 hrs/day and on three to five consecutive days over a 10-day time period. Dialysis treatment is performed by using the DIALIVE device provided by YAQRIT Ltd.

Also known as: YAQ 002

DIALIVE Liver Dialysis Device treatment arm

Eligibility Criteria

• Age: 18 Years - 81 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged ≥18 years ≤81yr who have given informed consent to participate in the study and are able to understand and comply with the requirements of the study (otherwise written informed consent must be obtained on behalf of the subject in accordance with local ethical and legal requirements).
• History indicative of alcohol-related cirrhosis based on clinical, radiological and/or histological evidence.
• History of an acute decompensating event (including but not limited to ascites, gastrointestinal bleeding, hepatic encephalopathy and/or acute bacterial infections), occurring within ≤6 weeks of screening.
• Subject with :
• ACLF Grade 1, 2 or 3a defined per the CLIF-C OF scoring system OR
• single hepatic organ failure for serum bilirubin \> 20 mg/dL (342 µmol/L) at screening and randomization, OR
• AKI-stage 1b (sCr \> 1.5 mg/dL or 134 µmol/L).
• Where a subject has received corticosteroids for alcohol-induced ACLF, is unresponsive to at least 7 days of treatment (where lack of response defined as Lille score \> 0.45 or steroids stopped before 7 days due to any complication such as infection). This refers to the first course of corticosteroid therapy only.

You may not qualify if:

• Co-infection with HIV and AIDS defining illness.
• Subjects with acute or sub-acute liver failure without underlying cirrhosis.
• Subjects with International Normalised Ratio (INR) \> 3
• ACLF 3b patients, i.e. ACLF with more than 3 organ failures.
• Subjects with cirrhosis who develop decompensation at any time in the post-operative period following partial partial liver resection or major non-liver surgery.
• Subjects with uncontrolled infection. Patients may be entered into the study provided antimicrobials have been administered for at least 48 hours with an appropriate response observed prior to randomization.
• Subjects with respiratory organ failure (as per CLIF-C OF scoring: PaO2/FiO2\< 200 mmHg or 27 kPa or SaO2/FiO2 \< 214).
• Subjects with haemodynamic instability:
• Subjects not considered appropriate for full active treatment including organ support or those with a Do Not Attempt Cardio-Pulmonary Resuscitation order (DNACPR).
• Subjects with active, or with a history of non hepatic malignancy unless adequately treated or in complete remission for five or more years.
• Patients with HCC outside Milan criteria.
• Significant systemic or major illness other than liver disease, including coronary artery disease, cerebrovascular disease, pulmonary disease, renal failure, serious psychiatric disease, that, in the opinion of the Investigator would preclude the subject from participating in and completing the study.
• Subject who has received any investigational drug or device within 30 days of dosing or who is scheduled to receive another investigational drug or device in the course of the study; concomitant observational studies are allowed.
• Evidence of uncontrolled seizures.
• Subjects diagnosed with Creutzfeldt-Jakob disease.

Sponsors & Collaborators

• Yaqrit Ltd: lead
• European Foundation for Chronic Liver Failure: collaborator
• University College, London: collaborator
• Fakkel bvba: collaborator

Study Sites (12)

university Hospital Graz

Graz, Austria

Location

University Hospital Erasmus

Brussels, Belgium

Location

University Hospital

Aarhus, Denmark

Location

Hôpital Beaujon

Clichy, France

Location

Paul Brousse Hospital

Villejuif, 94800, France

Location

University Hospital of Rostock

Rostock, 18051, Germany

Location

Fundeni Clinical Institute

Bucharest, Romania

Location

Hospital Clinic Barcelona

Barcelona, Spain

Location

University Hospital Gregorio Maragnon

Madrid, Spain

Location

Royal Free Hospital London NHS

London, Hampstead, NW3 2QG, United Kingdom

Location

university hospital BASILDON

Basildon, United Kingdom

Location

Queens Medical Centre

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (2)

• Lee KC, Baker LA, Stanzani G, Alibhai H, Chang YM, Jimenez Palacios C, Leckie PJ, Giordano P, Priestnall SL, Antoine DJ, Jenkins RE, Goldring CE, Park BK, Andreola F, Agarwal B, Mookerjee RP, Davies NA, Jalan R. Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study. J Hepatol. 2015 Sep;63(3):634-42. doi: 10.1016/j.jhep.2015.04.020. Epub 2015 May 1.

  PMID: 25937432 BACKGROUND

• Agarwal B, Canizares RB, Saliba F, Ballester MP, Tomescu DR, Martin D, Stadlbauer V, Wright G, Sheikh M, Morgan C, Alzola C, Lavin P, Green D, Kumar R, Sacleux SC, Schilcher G, Koball S, Tudor A, Minten J, Domenech G, Aragones JJ, Oettl K, Paar M, Waterstradt K, Bode-Boger SM, Ibanez-Samaniego L, Gander A, Ramos C, Chivu A, Stange J, Lamprecht G, Sanchez M, Mookerjee RP, Davenport A, Davies N, Pavesi M, Andreola F, Albillos A, Cordingley J, Schmidt H, Carbonell-Asins JA, Arroyo V, Fernandez J, Mitzner S, Jalan R. Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure. J Hepatol. 2023 Jul;79(1):79-92. doi: 10.1016/j.jhep.2023.03.013. Epub 2023 May 31.

  PMID: 37268222 DERIVED

Related Links

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MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Officials

• Banwari Agarwal, Dr

  Royal Free Hospital London NHS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DEVICE FEASIBILITY
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The design is a multi-centre, randomised, controlled, study to generate data for the evaluation of safety (as measured by the percentage of subjects who experience at least one serious adverse event (SAE)) and performance (as measured by lowering of the plasma endotoxin concentrations, and improved albumin function) of DIALIVE in 24 evaluable patients with Acute on Chronic Liver Failure (ACLF) versus standard of care (SOC). During the study the sample size was increased to include a total 30 evaluable patients.

Study Record Dates

• First Submitted: January 18, 2017
• First Posted: February 28, 2017
• Study Start: July 9, 2017
• Primary Completion: December 31, 2019
• Study Completion: January 15, 2020
• Last Updated: June 1, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); ES (2); AU (1); RO (1); DK (1); FR (2); DE (1); GB (3)