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

NCT02669680 | Completed DMC

• 1 other identifier: GRAFT
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 21

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.

Conditions

Acute-On-Chronic Liver Failure

Outcome Measures

Primary Outcomes (1)

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

  90 days

Secondary Outcomes (7)

• Overall survival time until the end of follow-up

  360 days

• Transplant-free survival time until the end of follow-up

  360 days

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

  90 days/360 days

• Infections (proven infection necessitating systemic use of antibiotics)

  90 days/360 days

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

  360 days

Study Arms (2)

G-CSF + Standard therapy

EXPERIMENTAL

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

Drug: G-CSF; Other: Standard therapy

Standard therapy

ACTIVE COMPARATOR

Standard care of acute-on-chronic liver failure

Other: Standard therapy

Interventions

G-CSF 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

Also known as: Filgrastim

G-CSF + Standard therapy

Standard therapy OTHER

G-CSF + Standard therapy; Standard therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Leipzig: lead

Study Sites (21)

University Hospital of Leipzig

Leipzig, Saxony, 04103, Germany

Location

Universitätsklinikum Aachen

Aachen, Germany

Location

Charité-Campus Virchow-Klinikum

Berlin, Germany

Location

Universitätsklinikum Bonn

Bonn, Germany

Location

Universitätsklinikum KÖLN

Cologne, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

Location

Universitätsklinikum Essen

Essen, Germany

Location

Klinikum der J.W. Goethe- Universität

Frankfurt, Germany

Location

Universitätsklinik Freiburg

Freiburg im Breisgau, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, Germany

Location

Universitätsklinikum des Saarlandes

Homburg, Germany

Location

Universitätsklinikum Jena

Jena, Germany

Location

Universitätsklinikum Schleswig-Holstein

Kiel, Germany

Location

HELIOS Park-Klinikum Leipzig

Leipzig, Germany

Location

Klinikum St. Georg gGmbH

Leipzig, Germany

Location

Universitätsklinikum Magdeburg AöR

Magdeburg, Germany

Location

Universitätsmedizin Mainz

Mainz, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

St. Josefs-Hospital

Wiesbaden, Germany

Location

Related Publications (1)

• 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.

  PMID: 34364917 RESULT

Related Links

• Link to the EU trials register to the GRAFT results

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Interventions

Granulocyte Colony-Stimulating Factor; Filgrastim; Standard of Care

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Thomas Berg, Prof.

  University Hospital of Leipzig;

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: January 22, 2016
• First Posted: February 1, 2016
• Study Start: February 1, 2016
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2020
• Last Updated: June 28, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (21)