Details

Autor(en) / Beteiligte

• Engelmann, Cornelius
• Herber, Adam
• Franke, Annegret
• Bruns, Tony
• Reuken, Philipp
• Schiefke, Ingolf
• Zipprich, Alexander
• Zeuzem, Stefan
• Goeser, Tobias
• Canbay, Ali
• Berg, Christoph
• Trebicka, Jonel
• Uschner, Frank E.
• Chang, Johannes
• Mueller, Tobias
• Aehling, Niklas
• Schmelzle, Moritz
• Splith, Katrin
• Lammert, Frank
• Lange, Christian M.
• Sarrazin, Christoph
• Trautwein, Christian
• Manns, Michael
• Häussinger, Dieter
• Pfeiffenberger, Jan
• Galle, Peter R.
• Schmiedeknecht, Anett
• Berg, Thomas

Titel

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

Ist Teil von

• Journal of hepatology, 2021-12, Vol.75 (6), p.1346-1354

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2021

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF. In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 μg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period. Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711–1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697–1.430; p = 0.992 and HR 1.058; 95% CI 0.727–1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation. In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. NCT02669680 Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies. [Display omitted] •G-CSF was expected to be a novel therapy for acute-on-chronic liver failure.•In this first multicenter, randomized phase II trial, G-CSF did not improve patient survival.•G-CSF was unable to reduce the rate of complications and did not improve organ function.