Trial document




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  DRKS00011572

Trial Description

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Title

Granulocyte colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure: A
multicentre randomized trial

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Trial Acronym

GRAFT

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URL of the Trial

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Brief Summary in Lay Language

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Brief Summary in Scientific Language

ACLF is a condition with dismal prognosis, for which apart from OLT (liver transplantation) no therapeutic options exist. A treatment approach that helps to recover from this acute intercurrent event and hereby improves the very poor short-term survival would be of major clinical importance. Stem cells play a major role in the process of hepatic regeneration. Their mobilization from the bone marrow due to G-CSF in patients with liver failure could be demonstrated in several phase I/II trials. Although an impact on the hepatic regenerative capacity was obvious, the results for clinical endpoints like patients´ survival and liver function were controversial [Di Campli 2007, Lorenzini 2008, Gaia 2006, Spahr 2008]. This was most likely due to the fact, that the observation period was limited and the power was inadequate for these endpoints. Recently two small randomized trials have shown the potential of G-CSF in this patient population markedly improving patients´ outcome [Garg 2012, Duan 2013]. However, these results need to be confirmed in a large multicenter Trial.

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Organizational Data

  •   DRKS00011572
  •   2017/03/14
  •   2016/01/29
  •   yes
  •   Approved
  •   415/15-ff, Ethikkommission an der Medizinischen Fakultät der Universität Leipzig
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Secondary IDs

  •   2015-002212-32 
  •   NCT02669680  (ClinicalTrials.gov )
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Health Condition or Problem studied

  •   K72.0 -  Acute and subacute hepatic failure
  •   acute-on-chronic liver failure
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Interventions/Observational Groups

  •   Application of G-CSF (Filgrastim) in combination with standard care of acute-on-chronic liver failure
    (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)
  •   Standard care of acute-on-chronic liver failure
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Parallel
  •   N/A
  •   N/A
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Primary Outcome

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

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Secondary Outcome

• Overall survival at 360 days
• Transplant-free survival at 360 days
• Complications of ACLF within 90 days/within 360 days (hepatorenal syndrome, variceal bleeding, ascites, hepatic encephalopathy)
• Infections within 90 days/within 360 days (proven infection necessitating systemic use of antibiotics)
• Liver function during the course of treatment and follow-up (MELD-Score, Child-Pugh-Score)
• Duration of initial hospital stay

Assessment of safety:
In addition to the complications of ACLF listed above, further AEs and SAEs will be assessed. Laboratory values reflecting liver function as well as infection related parameters will be monitored during the course of treatment and follow-up.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
  • University Medical Center 
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Recruitment

  •   Actual
  •   2016/02/29
  •   292
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

Acute-on-chronic liver failure according to the criteria defined by the CANONIC study [Moreau 2013] / age >= 18 years / Informed consent

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Exclusion Criteria

Prior not curatively treated or active malignancies / sickle cell disease / septic shock, defined by the following symptom complex: bacteraemia AND SIRS AND shock / WBC-count of > 50 x 109/L / known HIV infection / known intolerance to filgrastim / pregnancy, lactation or insufficient contraception / participation in other interventional clinical trials

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Addresses

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    • Universität Leipzig
    • Ritterstr. 26
    • 04109  Leipzig
    • Germany
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    • Universitätsklinikum LeipzigSektion Hepatologie; Abteilung für Innere Medizin, Neurologie, Dermatologie
    • Mr.  Prof.  Thomas  Berg 
    • Liebigstraße 20
    • 04103  Leipzig
    • Germany
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    • Universitätsklinikum Leipzig AöRSektion Hepatologie, Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum
    • Mr.  Prof.  Thomas  Berg 
    • Liebigstr. 20
    • 04103  Leipzig
    • Germany
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Sources of Monetary or Material Support

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    • Deutsche Forschungsgemeinschaft
    • Kennedyallee 40
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting stopped after recruiting started
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Trial Publications, Results and other Documents

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