Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke trial
Department of Neurology
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; www.clinicaltrial.gov). 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: http://www.clinicaltrials.gov. 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
Stroke; a journal of cerebral circulation
Ringelstein EB, Thijs V, Norrving B, Chamorro A, Aichner F, Grond M, Saver J, Laage R, Schneider A, Rathgeb F, Vogt G, Charisse G, Fiebach JB, Schwab S, Schabitz WR, Kollmar R, Fisher M, Brozman M, Skoloudik D, Gruber F, Serena Leal J, Veltkamp R, Kohrmann M, Berrouschot J. (2013). Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for Ischemic Stroke trial. UMass Chan Medical School Faculty Publications. https://doi.org/10.1161/STROKEAHA.113.001531. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/523