Granulocyte colony-stimulating factor in patients with acute ischemic stroke: results of the AX200 for ischemic stroke trial
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...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
20 Aug 2013
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| In: |
Stroke
Year: 2013, Volume: 44, Issue: 10, Pages: 2681-2687 |
| ISSN: | 1524-4628 |
| DOI: | 10.1161/STROKEAHA.113.001531 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1161/STROKEAHA.113.001531 Verlag, lizenzpflichtig, Volltext: https://www.ahajournals.org/doi/10.1161/STROKEAHA.113.001531 
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| Author Notes: | 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 |
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| 245 | 1 | 0 | |a Granulocyte colony-stimulating factor in patients with acute ischemic stroke |b results of the AX200 for ischemic stroke trial |c 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 |
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| 520 | |a 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. | ||
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