Acute-on-chronic liver failure (ACLF) MedDRA version: 20.1 Level: LLT Classification code 10068752 Term: Acute on chronic hepatic failure System Organ Class: 100000004871
Conditions
Interventions
Trade Name: Ratiograstim
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Proposed INN: FILGRASTIM
CAS Number: 121181-53-1
Concentration unit: mg/ml milligram(s)/milli
Sponsors
Universität Leipzig
Eligibility
Sex/Gender
All
Inclusion 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 =65 years) yes F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: From the clinical point of view, overall survival and transplant-free survival are the most relevant outcome measures. Thus, the primary endpoint of the study is transplant-free survival up to 90 days, with death and liver transplantation (OLT) counting as event;Secondary Objective: Beside overall survival and transplant-free survival time until the end of follow-up (see above) the following secondary endpoints will be evaluated: • Complications of ACLF (hepatorenal syndrome (HRS), variceal bleeding, ascites, hepatic encephalopathy (HE)) within 90 days/within 360 days. • 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 the initial hospital stay These further secondary endpoints have been chosen in order to better understand the impact of G-CSF administration on liver function and on the development of complications during the course of ACLF, especially the rate of infectious complications. The time frame 90 days reflects the treatment of the initial ACLF event, while 360 days analysis reflects long-term effects ;Primary end point(s): Transplant-free survival at 90 days, defined as time from randomization to death or OLT, censoring patients alive without OLT at the date of last information.;Timepoint(s) of evaluation of this end point: 90 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival at 360 days, defined as time from randomization to death, censoring patients alive at the date of last information (independent from an OLT done or not). • Transplant-free survival at 360 days • Complications of ACLF within 90 days/within 360 days. For each patient, every complication will be recorded including onset, HRS type 1/2, classification of ascites, and/or HE grade. • Infections within 90 days/within 360 days necessitating systemic use of antibiotics Complication (by highest scoring if applicable)/infections will be analysed per period of analysis regarding occurrence and number of episodes (if episodes delimitable) • Liver function during the course of treatment and follow-up ;Timepoint(s) of evaluation of this end point: 90 and 360 days | — |
Countries
Germany
Contacts
Public ContactThomas Berg
Universität Leipzig
Outcome results
None listed