UMass Chan Medical School Faculty Publications


Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke trial

UMMS Affiliation

Department of Neurology

Publication Date


Document Type



Adolescent; Adult; Aged; Aged, 80 and over; *Brain Infarction; Diffusion Magnetic Resonance Imaging; Female; *Granulocyte Colony-Stimulating Factor; effects; Humans; Male; Middle Aged; Recombinant Proteins; *Stroke; Time Factors


Cardiovascular Diseases | Neurology


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 microg/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 /=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.

DOI of Published Version



Stroke. 2013 Oct;44(10):2681-7. doi: 10.1161/STROKEAHA.113.001531. Epub 2013 Aug 20. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Stroke; a journal of cerebral circulation

PubMed ID