Details

Autor(en) / Beteiligte

• RINGELSTEIN, E. Bernd
• THIJS, Vincent
• VOGT, Gerhard
• CHARISSE, Gabriele
• FIEBACH, Jochen B
• SCHWAB, Stefan
• SCHÄBITZ, Wolf R
• KOLLMAR, Rainer
• FISHER, Marc
• BROZMAN, Miroslav
• SKOLOUDIK, David
• GRUBER, Franz
• NORRVING, Bo
• LEAL, Joaquin Serena
• VELTKAMP, Roland
• KÖHRMANN, Martin
• BERROUSCHOT, Jörg
• CHAMORRO, Angel
• AICHNER, Franz
• GROND, Martin
• SAVER, Jeff
• LAAGE, Rico
• SCHNEIDER, Armin
• RATHGEB, Frank

Titel

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

Ist Teil von

• Stroke (1970), 2013-10, Vol.44 (10), p.2681-2687

Ort / Verlag

Hagerstown, MD: Lippincott Williams & Wilkins

Erscheinungsjahr

2013

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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; www.clinicaltrial.gov). 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). 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. 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. http://www.clinicaltrials.gov. Unique identifier: NCT00927836.