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

NCT ID: NCT03065699

Last Updated: 2021-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-09
• Study Completion Date: 2020-01-15

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).

Detailed Description

The First-In-Man study will evaluate the safety and performance of DIALIVE Liver Dialysis Device in Acute on Chronic Liver Failure (ACLF) patients and will compare the outcome with patients treated under standard of care (SOC).

The hypothesis is that DIALIVE will significantly improve the prognosis of ACLF patients by modulating systemic inflammation.

The target patient population are men and women ≥18 years, ≤81yr. Patients with ACLF grade 1 and ACLF grade 2 on the background of alcoholic cirrhosis. During the study, inclusion criteria were expanded to include also AKI-1 and ACLF 3a patients. Treatment will be undertaken in an intensive care (ICU) or renal dialysis unit setting if the patients are randomised to the DIALIVE treatment arm. For patients 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.

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 733057.

Conditions

Acute on Chronic Liver Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DEVICE_FEASIBILITY
• Blinding Strategy: NONE

Study Groups

Standard of Care

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

DIALIVE Liver Dialysis Device treatment arm

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.

Group Type: ACTIVE_COMPARATOR

DIALIVE Liver Dialysis Device

Intervention Type: 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.

Interventions

DIALIVE Liver Dialysis 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.

Intervention Type: DEVICE

Other Intervention Names

YAQ 002

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• Co-infection with HIV and AIDS defining illness.
• Subjects with acute or sub-acute liver failure without underlying cirrhosis.
• Subjects with severe thrombocytopaenia, defined by the platelet count of < 40,000 / mm3 or rapid reduction in platelet count (> 50% reduction) 24 hrs prior to inclusion.
• 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:

i) persistent hypotension (mean arterial pressure < 65 mmHg) with evidence of tissue hypoperfusion, not responsive to volume resuscitation and/or low dose vasopressor support; ii) a norepinephrine dose of > 0.2 µg/kg/min, or a second pressor (terlipressin for variceal haemorrhage and/or hepato-renal syndrome does not count as pressor, unless it is specifically used to treat systemic hypotension) at screening or randomization. Patients can be reconsidered for study inclusion after at least a 24 hour period of norepinephrine requirement < 0.2 µg/kg/min.

• 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.
• In females: known pregnancy or lactating.
• Subjects weighing less than 30 kg (as per contra-indications of oXiris and septeX)
• Where subjectspresent with a known allergy to heparine of have type II thrombocytopaenia caused by heparin (HIT syndrome type II)
• In the opinion of the investigator, it is unsafe for the patient to be considered for the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 81 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Foundation for Chronic Liver Failure

UNKNOWN

Sponsor Role: collaborator

University College, London

OTHER

Sponsor Role: collaborator

Fakkel bvba

INDUSTRY

Sponsor Role: collaborator

Yaqrit Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Banwari Agarwal, Dr

Role: PRINCIPAL_INVESTIGATOR

Royal Free Hospital London NHS

Locations

university Hospital Graz

Graz, , Austria

University Hospital Erasmus

Brussels, , Belgium

University Hospital

Aarhus, , Denmark

Hôpital Beaujon

Clichy, , France

Paul Brousse Hospital

Villejuif, , France

University Hospital of Rostock

Rostock, , Germany

Fundeni Clinical Institute

Bucharest, , Romania

Hospital Clinic Barcelona

Barcelona, , Spain

University Hospital Gregorio Maragnon

Madrid, , Spain

Royal Free Hospital London NHS

London, Hampstead, United Kingdom

university hospital BASILDON

Basildon, , United Kingdom

Queens Medical Centre

Nottingham, , United Kingdom

Countries

Austria; Belgium; Denmark; France; Germany; Romania; Spain; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 25937432 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37268222 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Study Documents

Document Type: Clinical Study Report

A summary of the final Clinical Study Report can be obtained through request to: 1. YAQRIT Ltd, attention of Daniel Green, CEO (daniel.green@yaqrit.com) or Carrie Morgan (carrie.morgan@yaqrit.com) 2. FAKKEL bvba, attention of Jaak Minten, CEO (info@fakkel-bvba.com)

View Document

Related Links

http://yaqrit.com

webpage legal responsible partner \& spnosor

Other Identifiers

CIV-16-08-016644

Identifier Type: OTHER

Identifier Source: secondary_id

YAQ-002

Identifier Type: -

Identifier Source: org_study_id