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Granulocyte Colony Stimulating Factor (G-CSF) to Treat Acute-on-chronic Liver Failure

Sponsor
University of Leipzig (Other)
Overall Status
Completed
CT.gov ID
NCT02669680
Collaborator
(none)
176
Enrollment
21
Locations
2
Arms
49
Actual Duration (Months)
8.4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Multicentre, open, randomised, and controlled trial conducted in patients diagnosed with acute on chronic liver failure (ACLF) who meet inclusion/exclusion criteria.The objective of GRAFT-trial is to evaluate efficacy and safety of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in patients with ACLF. All patients will receive standard medical care for ACLF according to the guidelines. Patients in the experimental arm additional receive subcutaneous injections of G-CSF.

Condition or Disease Intervention/Treatment Phase
N/A

Detailed Description

The acute on chronic liver failure (ACLF) is characterised by a severe deterioration of liver function due to a precipitating event on top of an underlying chronic liver disease. As therapeutic options are limited the mortality rate lies between 40 and 80% at 3 months. The granulocyte colony-stimulating factor (G-CSF) mobilized stem- as well as immune cells and improved liver function in preclinical trials. G-CSF treatment reduced the rate of infectious complications and significantly improved patients´ survival in acute on chronic liver failure, shown recently in small randomised studies. Thus, G-CSF is a promising treatment option that needs to be evaluated in a multi-centre controlled trial. The GRAFT trial will randomise patients with ACLF between standard of care with and without G-CSF. All participants will be followed for 12 months in order to evaluate safety and efficacy of G-CSF. If successful, the GRAFT trial has the potential to change clinical practice in acute on chronic liver failure.

Study Design

Study Type:
Interventional
Actual Enrollment :
176 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Granulocyte Colony Stimulating Factor (G-CSF) to Treat Acute-on-chronic Liver Failure: A Multicentre Randomized Trial
Actual Study Start Date :
Feb 1, 2016
Actual Primary Completion Date :
Mar 1, 2020
Actual Study Completion Date :
Mar 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: G-CSF + Standard therapy

Standard care of acute-on-chronic liver failure and application of G-CSF

Drug: G-CSF
G-CSF subcutaneously, 5 μg/kg daily on day 0-4, then every 3rd day over 26 days (days 7, 10, 13, 16, 19, 22, 25) = 12 doses
Other Names:
  • Filgrastim

    • Other: Standard therapy
    Active Comparator: Standard therapy

    Standard care of acute-on-chronic liver failure

    Other: Standard therapy

    Outcome Measures

    Primary Outcome Measures

    1. Transplant-free survival up to 90 days (death or transplant count as events) [90 days]

    Secondary Outcome Measures

    1. Overall survival time until the end of follow-up [360 days]

    2. Transplant-free survival time until the end of follow-up [360 days]

    3. Complications of ACLF (hepatorenal syndrome (HRS), variceal bleeding, ascites, hepatic encephalopathy (HE)) [90 days/360 days]

    4. Infections (proven infection necessitating systemic use of antibiotics) [90 days/360 days]

    5. Liver function - assessed by MELD-Score - during the course of treatment and follow-up [360 days]

    6. Liver function - assessed by Child-Pugh-Score - during the course of treatment and follow-up [360 days]

    7. Duration of the initial hospital stay [up to 360 days]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Acute-on-chronic liver failure (ACLF) according to the consensus criteria recently defined by the CANONIC study group [Moreau 2013]. Patients with acute decompensation of cirrhosis [defined as acute development of one or more of the following: ascites (onset and/or worsening), hepatic encephalopathy (onset and/or worsening), gastrointestinal haemorrhage, bacterial infection] are classified as ACLF if one of the following applies:

    • single kidney failure (serum creatinine level ≥ 2 mg/dl) or

    • single failure of one of the following organ systems: liver, coagulation, circulation, or respiration, together with a serum creatinine level ranging from 1.5 to < 2.0 mg/dl and/or mild to moderate hepatic encephalopathy or

    • single cerebral failure together with serum creatinine level ranging from 1.5 to < 2.0 mg/dl or

    • two or more organ failures. Organ failures are defined according to the CLIF-C OFs [Jalan 2014].

    1. Age ≥ 18 years, male or female

    2. Written informed consent from patient, legal or authorized representative or a confirmation of justification of trial participation by an independent medical consultant PLEASE NOTE: In case of confirmation by the independent medical consultant a deferred informed consent from patient, legal or authorized representative has to be given

    Exclusion Criteria:

    1. Prior not curatively treated or active malignancies

    2. Sickle cell disease

    3. septic shock, defined by the following symptom complex: bacteraemia AND SIRS AND shock

    4. WBC-count of > 50 x 109/L

    5. Known HIV infection

    6. Known intolerance to filgrastim

    7. Suspected lack of compliance

    8. Pregnant or nursing women

    9. Fertile women (within two years of their last menstruation) without appropriate contraceptive measures (implanon, injections, oral contraceptives, intrauterine devices, partner with vasectomy) while participating in the trial (participants using a hormone-based method have to be informed of possible effects from the trial medication on contraception).

    10. Participation in other interventional trials

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University Hospital of Leipzig Leipzig Sachsen Germany 04103
    2 Universitätsklinikum Aachen Aachen Germany
    3 Charité-Campus Virchow-Klinikum Berlin Germany
    4 Universitätsklinikum Bonn Bonn Germany
    5 Universitätsklinikum Düsseldorf Düsseldorf Germany
    6 Universitätsklinikum Essen Essen Germany
    7 Klinikum der J.W. Goethe- Universität Frankfurt Germany
    8 Universitätsklinik Freiburg Freiburg Germany
    9 Universitätsklinikum Halle (Saale) Halle Germany
    10 Medizinische Hochschule Hannover Hannover Germany
    11 Universitätsklinikum Heidelberg Heidelberg Germany
    12 Universitätsklinikum des Saarlandes Homburg Germany
    13 Universitätsklinikum Jena Jena Germany
    14 Universitätsklinikum Schleswig-Holstein Kiel Germany
    15 Universitätsklinikum KÖLN Köln Germany
    16 HELIOS Park-Klinikum Leipzig Leipzig Germany
    17 Klinikum St. Georg gGmbH Leipzig Germany
    18 Universitätsklinikum Magdeburg AöR Magdeburg Germany
    19 Universitätsmedizin Mainz Mainz Germany
    20 Universitätsklinikum Tübingen Tübingen Germany
    21 St. Josefs-Hospital Wiesbaden Germany

    Sponsors and Collaborators

    • University of Leipzig

    Investigators

    • Study Director: Thomas Berg, Prof., University Hospital of Leipzig;

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Thomas Berg, Prof. Dr. med., University of Leipzig
    ClinicalTrials.gov Identifier:
    NCT02669680
    Other Study ID Numbers:
    • GRAFT
    First Posted:
    Feb 1, 2016
    Last Update Posted:
    Jun 28, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:
    Liver Failure
    Hepatic Insufficiency
    End Stage Liver Disease
    Acute-On-Chronic Liver Failure
    Lenograstim

    Study Results

    No Results Posted as of Jun 28, 2022