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

NCT ID: NCT02669680

Last Updated: 2022-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 176 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2020-03-31

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.

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.

Conditions

Acute-On-Chronic Liver Failure

Study Design

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

Study Groups

G-CSF + Standard therapy

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

Group Type: EXPERIMENTAL

G-CSF

Intervention Type: DRUG

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 therapy

Intervention Type: OTHER

Standard therapy

Standard care of acute-on-chronic liver failure

Group Type: ACTIVE_COMPARATOR

Standard therapy

Intervention Type: OTHER

Interventions

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

Intervention Type: DRUG

Standard therapy

Intervention Type: OTHER

Other Intervention Names

Filgrastim

Eligibility Criteria

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].

2. Age ≥ 18 years, male or female

3. 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

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

Sponsors

University of Leipzig

OTHER

Sponsor Role: lead

Responsible Party

Thomas Berg

Prof. Dr. med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Thomas Berg, Prof.

Role: STUDY_DIRECTOR

University Hospital of Leipzig;

Locations

University Hospital of Leipzig

Leipzig, Saxony, Germany

Universitätsklinikum Aachen

Aachen, , Germany

Charité-Campus Virchow-Klinikum

Berlin, , Germany

Universitätsklinikum Bonn

Bonn, , Germany

Universitätsklinikum KÖLN

Cologne, , Germany

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Universitätsklinikum Essen

Essen, , Germany

Klinikum der J.W. Goethe- Universität

Frankfurt, , Germany

Universitätsklinik Freiburg

Freiburg im Breisgau, , Germany

Universitätsklinikum Halle (Saale)

Halle, , Germany

Medizinische Hochschule Hannover

Hanover, , Germany

Universitätsklinikum Heidelberg

Heidelberg, , Germany

Universitätsklinikum des Saarlandes

Homburg, , Germany

Universitätsklinikum Jena

Jena, , Germany

Universitätsklinikum Schleswig-Holstein

Kiel, , Germany

HELIOS Park-Klinikum Leipzig

Leipzig, , Germany

Klinikum St. Georg gGmbH

Leipzig, , Germany

Universitätsklinikum Magdeburg AöR

Magdeburg, , Germany

Universitätsmedizin Mainz

Mainz, , Germany

Universitätsklinikum Tübingen

Tübingen, , Germany

St. Josefs-Hospital

Wiesbaden, , Germany

Countries

Germany

References

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.

Reference Type: RESULT

PMID: 34364917 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Related Links

https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-002212-32/results

Link to the EU trials register to the GRAFT results

Other Identifiers

GRAFT

Identifier Type: -

Identifier Source: org_study_id