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

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ClinicalTrials.gov Identifier: NCT03065699
Recruitment Status : Recruiting
First Posted : February 28, 2017
Last Update Posted : July 26, 2019
Sponsor:
Collaborators:
European Foundation for Chronic Liver Failure
University College, London
Fakkel bvba
Information provided by (Responsible Party):
Yaqrit Ltd

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).

Condition or disease Intervention/treatment Phase
Acute on Chronic Liver Failure Device: DIALIVE Liver Dialysis Device Not Applicable

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. 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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).
Masking: None (Open Label)
Primary Purpose: Device Feasibility
Official Title: A Multi-centre, Randomised Controlled Study, to Evaluate the Safety and Performance of The DIALIVE Liver Dialysis Device (LDD) in Patients With Acute on Chronic Liver Failure (ACLF) Versus Standard of Care (SOC)
Actual Study Start Date : July 9, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : April 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dialysis

Arm Intervention/treatment
No Intervention: 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.
Active Comparator: 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.
Device: 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.
Other Name: YAQ 002




Primary Outcome Measures :
  1. Safety of DIALIVE in terms of percentage of ACLF patients experiencing serious adverse events during DIALIVE treatment period. [ Time Frame: Treatment period is from 1 to 10 days post-randomization. ]

    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.


  2. Safety of DIALIVE in terms of percentage of ACLF patients who discontinued treatment due to severe adverse event. [ Time Frame: Treatment period is from 1 to 10 days post-randomization. ]
    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)


Secondary Outcome Measures :
  1. Performance of DIALIVE by assessing removal of endotoxins. [ Time Frame: End of DIALIVE treatment (max 10 days after randomization) ]

    To evaluate the performance of the DIALIVE device in patients with ACLF (DIALIVE arm only). Outcome measure is :

    - Change in Plasma endotoxin concentrations between end of treatment with DIALIVE and the beginning of treatment with DIALIVE (Day 1).

    TV: 40% reduction; AV: 20% reduction


  2. Performance of DIALIVE by assessing removal of albumin. [ Time Frame: End of DIALIVE treatment (max 10 days after randomization) ]

    To evaluate the performance of the DIALIVE device in patients with ACLF (DIALIVE arm only). Outcome measure is :

    - Change in Albumin function (Human non-mercapt albumin -2 (HNA-2) / Human mercapt albumin (HMA ratio) between end of treatment with DIALIVE and the beginning of treatment with DIALIVE (Day 1)


  3. Change in Clinical Parameters by DIALIVE treatment (ACLF grade and score) between treatment arms. [ Time Frame: Treatment period is from 1 to 10 days post-randomization ]

    Evaluate the improvement in clinical parameters between Acute on Chronic Liver Failure (ACLF) patients receiving DIALIVE treatment vs Standard of Care. Outcome measure is:

    - Change in CLIF-C score (Chronic LIver Failure Consortium)


  4. Change in Clinical Parameters by DIALIVE treatment (ACLF grade) between treatment arms. [ Time Frame: Treatment period is from 1 to 10 days post-randomization ]

    Evaluate the improvement in clinical parameters between Acute on Chronic Liver Failure (ACLF) patients receiving DIALIVE treatment vs Standard of Care. Outcome measure is:

    - Change in ACLF Grade


  5. Change in mortality between treatment arms. [ Time Frame: At day 28 post-randomization. ]
    The outcome measure is the difference in mortality between the DIALIVE treatment arm and the Standard of Care arm at day 28 post-randomization.

  6. Change in Clinical Parameters by DIALIVE treatment (CLIF-C score) between treatment arms. [ Time Frame: Treatment period is from 1 to 10 days post-randomization ]

    Evaluate the improvement in clinical parameters between Acute on Chronic Liver Failure (ACLF) patients receiving DIALIVE treatment vs Standard of Care. Outcome measure is:

    - Change in CLIF-C score (Chronic LIver Failure Consortium)



Other Outcome Measures:
  1. Efficacy of the DIALIVE for liver function: changes in MELD score [ Time Frame: Treatment period is from 1 to 10 days post-randomization ]

    Outcome measure as compared between SoC and DIALIVE arm is:

    - Liver: Changes in MELD score, plasma/serum cCK18/M30 and flCK18/M65 (markers of liver cell death).

    Model for End-Stage Liver Disease (MELD) Scoring Systems.


  2. Efficacy of the DIALIVE for kidney function: changes in creatine and NGAL [ Time Frame: Treatment period is from 1 to 10 days post-randomization ]

    Outcome measure as compared between SoC and DIALIVE arm is:

    - Kidney: Changes in serum creatinine and urinary NGAL (Neutrophil gelatinase-associated lipocalin - marker of kidney injury).


  3. Efficacy of the DIALIVE for brain function: changes in West Haven Criteria [ Time Frame: Treatment period is from 1 to 10 days post-randomization ]

    Outcome measure as compared between SoC and DIALIVE arm is:

    - Brain: West Haven Criteria to assess changes in severity of hepatic encephalopathy.


  4. Efficacy of the DIALIVE for immune function. [ Time Frame: Treatment period is from 1 to 10 days post-randomization ]

    Outcome measure as compared between SoC and DIALIVE arm is:

    - Immune function: Incidence of Infection. Changes in white cell count and plasma-induced neutrophil function (Phagoburst and Phagotest), serum CRP and cytokines (TNF-α, IL-6, IL-8, IL-10, IL1RA).




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 81 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 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 meets the definition of ACLF Grade 1 or Grade 2 (using the CLIF-C OF score system [Moreau et al. Gastroenterology 2013; Jalan et al. J Hepatol 2014]).
  • 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 a reduction in bilirubin <25% over a 7 day treatment period).
  • No evidence of untreated infection. Where a subject has one or more underlying infections, he/she may be entered into the study provided that appropriate antibiotics (as determined by the investigator) have been administered for at least 48 hours prior to randomisation.

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 cirrhosis who develop decompensation at any time in the post-operative period following partial hepatectomy.
  • Subjects with evidence of uncontrolled infection.
  • Subjects with chronic and/or pre-existing kidney disease defined as eGFR (estimated glomerular filtration rate) <30 mL/min for 3 months or longer prior to screening.
  • Subjects with hypotension requiring the use of vasopressors (other than terlipressin for the treatment of hepatorenal syndrome, or following variceal bleeding).
  • Subjects with evidence of significant and/or uncontrolled bleeding; patients with gastrointestinal bleeding can be enrolled 48 hours after the control of bleeding.
  • Hepatic encephalopathy Grade 3 or 4 (West Haven Criteria).
  • Subjects with active or 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.
  • Any 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.
  • Uncontrolled seizures.
  • Subjects diagnosed with Creutzfeldt-Jakob disease.
  • If female: known pregnancy or lactating.
  • Subjects unable to consent for themselves.
  • patients with a known allergy to heparine of have type II thrombocytopaenia caused by heparin (HIT syndrome type II)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03065699


Contacts
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Contact: Jaak Minten, Ph.D. +32-475-923-149 jaak.minten@fakkel-bvba.com
Contact: Cindy Rochus, MSc +32-495-924-296 cindy.rochus@fakkel-bvba.com

Locations
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Austria
university Hospital Graz Recruiting
Graz, Austria
Contact: Vanessa Stadlbauer, Prof         
Belgium
University Hospital Erasmus Recruiting
Brussels, Belgium
Contact: Thierry Gustot, Prof         
Denmark
University Hospital Not yet recruiting
Aarhus, Denmark
Contact: Niels Kristian Aagaard, Prof         
University Hospital Rigs Not yet recruiting
Copenhagen, Denmark
Contact: Fin Stolzen Larsen, Prof         
France
Hôpital Beaujon Recruiting
Clichy, France
Contact: François Durand, M.D.    +33 (0)1 40 87 55 48    francois.durand@aphp.fr   
Paul Brousse Hospital Recruiting
Villejuif, France, 94800
Contact: Fouzi Saliba, Prof    +33-145-59-64-12    faouzi.saliba@aphp.fr   
Germany
University Hospital Not yet recruiting
Leipzig, Germany
Contact: Thomas Berg, Prof         
University Hospital of Rostock Recruiting
Rostock, Germany, 18051
Contact: Steffen Mitzner, Prof    +49 381 494-7730    steffen.mitzner@uni-rostock.de   
Romania
Fundeni Clinical Institute Recruiting
Bucharest, Romania
Contact: Dana Tomescu, Prof         
Spain
Hospital Clinic Barcelona Recruiting
Barcelona, Spain
Contact: Javier Fernandéz, M.D.       JFDEZ@clinic.cat   
University Hospital Gregorio Maragnon Recruiting
Madrid, Spain
Contact: Raphael Banares, Prof    +34-609-042-961    rbanares@telefonica.net   
United Kingdom
Royal Free Hospital London NHS Recruiting
London, Hampstead, United Kingdom, NW3 2QG
Contact: Daniel Martin, Dr       daniel.martin@ucl.ac.uk   
Queen Elizabeth Hospital Withdrawn
Birmingham, United Kingdom, B15 2TH
Queens Medical Centre Recruiting
Nottingham, United Kingdom, NG7 2UH
Contact: Guruprasad Aithal, Prof    +44-115 924 9924 ext 63822    guru.aithal@nuh.nhs.uk   
Sponsors and Collaborators
Yaqrit Ltd
European Foundation for Chronic Liver Failure
University College, London
Fakkel bvba
Investigators
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Principal Investigator: Banwari Agarwal, Dr Royal Free Hospital London NHS

Additional Information:
Publications:
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Responsible Party: Yaqrit Ltd
ClinicalTrials.gov Identifier: NCT03065699     History of Changes
Other Study ID Numbers: YAQ-002
CIV-16-08-016644 ( Other Identifier: EUDAMED number issued by MHRA )
First Posted: February 28, 2017    Key Record Dates
Last Update Posted: July 26, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Only anonymized clinical data can be shared out of central database according to the H2020 project plan.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yaqrit Ltd:
Medical device
Liver dialysis
Haemofilter
ACLF
Additional relevant MeSH terms:
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Liver Failure
Hepatic Insufficiency
End Stage Liver Disease
Acute-On-Chronic Liver Failure
Liver Diseases
Digestive System Diseases
Liver Failure, Acute
Liver Extracts
Hematinics