Granulocyte colony-stimulating factor in patients with acute ischemic stroke

• Verfasst von: Ringelstein, Erich B. [VerfasserIn]
• Verfasst von: Thijs, Vincent [VerfasserIn]
• Verfasst von: Norrving, Bo [VerfasserIn]
• Verfasst von: Chamorro, Angel [VerfasserIn]
• Verfasst von: Aichner, Franz [VerfasserIn]
• Verfasst von: Grond, Martin [VerfasserIn]
• Verfasst von: Saver, Jeff [VerfasserIn]
• Verfasst von: Laage, Rico [VerfasserIn]
• Verfasst von: Schneider, Armin [VerfasserIn]
• Verfasst von: Rathgeb, Frank [VerfasserIn]
• Verfasst von: Vogt, Gerhard [VerfasserIn]
• Verfasst von: Charissé, Gabriele [VerfasserIn]
• Verfasst von: Fiebach, Jochen B. [VerfasserIn]
• Verfasst von: Schwab, Stefan [VerfasserIn]
• Verfasst von: Schäbitz, Wolf R. [VerfasserIn]
• Verfasst von: Kollmar, Rainer [VerfasserIn]
• Verfasst von: Fisher, Marc [VerfasserIn]
• Verfasst von: Brozman, Miroslav [VerfasserIn]
• Verfasst von: Skoloudik, David [VerfasserIn]
• Verfasst von: Gruber, Franz [VerfasserIn]
• Verfasst von: Leal, Joaquin Serena [VerfasserIn]
• Verfasst von: Veltkamp, Roland [VerfasserIn]
• Verfasst von: Köhrmann, Martin [VerfasserIn]
• Verfasst von: Berrouschot, Jörg [VerfasserIn]
• Titel: Granulocyte colony-stimulating factor in patients with acute ischemic stroke
• Titelzusatz: results of the AX200 for ischemic stroke trial
• Verf.angabe: E. Bernd Ringelstein, MD; Vincent Thijs, MD; Bo Norrving, MD; Angel Chamorro, MD; Franz Aichner, MD; Martin Grond, MD; Jeff Saver, MD; Rico Laage, PhD; Armin Schneider, MD; Frank Rathgeb, MD; Gerhard Vogt, MD; Gabriele Charissé, MA; Jochen B. Fiebach, MD; Stefan Schwab, MD; Wolf R. Schäbitz, MD; Rainer Kollmar, MD; Marc Fisher, MD; Miroslav Brozman, MD; David Skoloudik, MD; Franz Gruber, MD; Joaquin Serena Leal, MD; Roland Veltkamp, MD; Martin Köhrmann, MD; Jörg Berrouschot, MD; for the AXIS 2 Investigators
• E-Jahr: 2013
• Jahr: 20 Aug 2013
• Umfang: 7 S.
• Fussnoten: Gesehen am 13.01.2022
• Titel Quelle: Enthalten in: Stroke
• Ort Quelle: New York, NY : Association, 1970
• Jahr Quelle: 2013
• Band/Heft Quelle: 44(2013), 10 vom: Okt., Seite 2681-2687
• ISSN Quelle: 1524-4628
• DOI: doi:10.1161/STROKEAHA.113.001531
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: clinical trial
• Sach-SW: G-CSF
• Sach-SW: hematopoietic growth factor
• Sach-SW: leukocytes
• Sach-SW: MRI
• Sach-SW: phase II
• Sach-SW: stroke
• K10plus-PPN: 1785972057

Abstract

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; 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). 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.