Granulocyte Colony-Stimulating Factor in Patients With Acute Ischemic Stroke: Results of the AX200 for Ischemic Stroke Trial

Stroke. 2013 Oct;44(10):2681-7. doi: 10.1161/STROKEAHA.113.001531. Epub 2013 Aug 20.


Background and purpose: Granulocyte colony-stimulating factor (G-CSF; AX200; Filgrastim) is a stroke drug candidate with excellent preclinical evidence for efficacy. A previous phase IIa dose-escalation study suggested potential efficacy in humans. The present large phase IIb trial was powered to detect clinical efficacy in acute ischemic stroke patients.

Methods: G-CSF (135 µg/kg body weight intravenous over 72 hours) was tested against placebo in 328 patients in a multinational, multicenter, randomized, and placebo-controlled trial (NCT00927836; Main inclusion criteria were ≤9-hour time window after stroke onset, infarct localization in the middle cerebral artery territory, baseline National Institutes of Health Stroke Scale score range of 6 to 22, and baseline diffusion-weighted imaging lesion size ≥15 mL. Primary and secondary end points were the modified Rankin scale score and the National Institutes of Health Stroke Scale score at day 90, respectively. Data were analyzed using a prespecified model that adjusted for age, National Institutes of Health Stroke Scale score at baseline, and initial infarct volume (diffusion-weighted imaging).

Results: G-CSF treatment failed to meet the primary and secondary end points of the trial. For additional end points such as mortality, Barthel index, or infarct size at day 30, G-CSF did not show efficacy either. There was, however, a trend for reduced infarct growth in the G-CSF group. G-CSF showed the expected peripheral pharmacokinetic and pharmacodynamic profiles, with a strong increase in leukocytes and monocytes. In parallel, the cytokine profile showed a significant decrease of interleukin-1.

Conclusions: G-CSF, a novel and promising drug candidate with a comprehensive preclinical and clinical package, did not provide any significant benefit with respect to either clinical outcome or imaging biomarkers.

Clinical trial registration url: Unique identifier: NCT00927836.

Keywords: G-CSF; MRI; clinical trial; hematopoietic growth factor; leukocytes; phase II; stroke.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Infarction* / diagnostic imaging
  • Brain Infarction* / drug therapy
  • Brain Infarction* / metabolism
  • Diffusion Magnetic Resonance Imaging / methods
  • Female
  • Filgrastim
  • Granulocyte Colony-Stimulating Factor* / administration & dosage
  • Granulocyte Colony-Stimulating Factor* / adverse effects
  • Granulocyte Colony-Stimulating Factor* / pharmacokinetics
  • Humans
  • Male
  • Middle Aged
  • Radiography
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / pharmacokinetics
  • Stroke* / diagnostic imaging
  • Stroke* / drug therapy
  • Stroke* / metabolism
  • Time Factors


  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Filgrastim

Associated data