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Acute-On-Chronic Liver FailureNCT02669680

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

A study testing G-CSF and Standard therapy in people with Acute-On-Chronic Liver Failure, run by University of Leipzig at 21 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute-On-Chronic Liver Failure
What is being tested?
G-CSF and Standard therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
176 participants
Where
21 sitesGermany
Study dates
Feb 2016to Mar 2020
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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].
  • Age ≥ 18 years, male or female
  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • Suspected lack of compliance
  • Pregnant or nursing women
  • 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).
  • Participation in other interventional trials

Trial locations and contacts

21 sites in 1 country.

21 sites in 1 country

Germany21 sites

  • Universitätsklinikum Aachen

    Aachen

  • Charité-Campus Virchow-Klinikum

    Berlin

  • Universitätsklinikum Bonn

    Bonn

  • Universitätsklinikum KÖLN

    Cologne

  • Universitätsklinikum Düsseldorf

    Düsseldorf

  • Universitätsklinikum Essen

    Essen

  • Klinikum der J.W. Goethe- Universität

    Frankfurt

  • Universitätsklinik Freiburg

    Freiburg im Breisgau

  • Universitätsklinikum Halle (Saale)

    Halle

  • Medizinische Hochschule Hannover

    Hanover

  • Universitätsklinikum Heidelberg

    Heidelberg

  • Universitätsklinikum des Saarlandes

    Homburg

  • Universitätsklinikum Jena

    Jena

  • Universitätsklinikum Schleswig-Holstein

    Kiel

  • University Hospital of Leipzig

    Leipzig, Saxony, 04103

  • HELIOS Park-Klinikum Leipzig

    Leipzig

  • Klinikum St. Georg gGmbH

    Leipzig

  • Universitätsklinikum Magdeburg AöR

    Magdeburg

  • Universitätsmedizin Mainz

    Mainz

  • Universitätsklinikum Tübingen

    Tübingen

  • St. Josefs-Hospital

    Wiesbaden

Other trials in Germany

About this study

Official title: Granulocyte Colony Stimulating Factor (G-CSF) to Treat Acute-on-chronic Liver Failure: A Multicentre Randomized Trial

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.

Read the 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.

Being tested
G-CSF, Standard therapy
Medical subject headings
Acute-On-Chronic Liver Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • G-CSFDrug

    Also called Filgrastim

    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 therapyOther

Study groups in NCT02669680
Study groupRoleWhat they receive
G-CSF + Standard therapyExperimentalStandard care of acute-on-chronic liver failure and application of G-CSF
Receives: Drug: G-CSF; Other: Standard therapy
Standard therapyActive comparatorStandard care of acute-on-chronic liver failure
Receives: Other: Standard therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 90 days

Secondary outcomes (7)

  1. Overall survival time until the end of follow-up

    Measured: 360 days

  2. Transplant-free survival time until the end of follow-up

    Measured: 360 days

  3. Complications of ACLF (hepatorenal syndrome (HRS), variceal bleeding, ascites, hepatic encephalopathy (HE))

    Measured: 90 days/360 days

  4. Infections (proven infection necessitating systemic use of antibiotics)

    Measured: 90 days/360 days

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

    Measured: 360 days

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

    Measured: 360 days

  7. Duration of the initial hospital stay

    Measured: up to 360 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2016 (estimated)
  2. Study startFeb 2016
  3. Primary completionMar 2020
  4. Study completionMar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
176 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02669680
Sponsor's protocol ID
GRAFT
Status last verified
Jun 2022
First submitted
22 Jan 2016
Last updated
28 Jun 2022
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Engelmann C, Herber A, Franke A, Bruns T, Reuken P, Schiefke I, Zipprich A, Zeuzem S, Goeser T, Canbay A, Berg C, Trebicka J, Uschner FE, Chang J, Mueller T, Aehling N, Schmelzle M, Splith K, Lammert F, Lange CM, Sarrazin C, Trautwein C, Manns M, Haussinger D, Pfeiffenberger J, Galle PR, Schmiedeknecht A, Berg T. Granulocyte-colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure: A multicenter randomized trial (GRAFT study). J Hepatol. 2021 Dec;75(6):1346-1354. doi: 10.1016/j.jhep.2021.07.033. Epub 2021 Aug 5.

    PubMed 34364917

Questions about this trial

What is this clinical trial studying?

A study testing G-CSF and Standard therapy in people with Acute-On-Chronic Liver Failure, run by University of Leipzig at 21 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Transplant-free survival up to 90 days (death or transplant count as events) (time frame: 90 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02669680, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2022.

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