Granulocyte colony-stimulating factor in patients with acute ischemic stroke : results of the AX200 for Ischemic Stroke trial
| Autor: | Ringelstein, E Bernd, Thijs, Vincent, Norrving, Bo, Chamorro, Angel, Aichner, Franz, Grond, Martin, Saver, Jeff, Laage, Rico, Schneider, Armin, Rathgeb, Frank, Vogt, Gerhard, Charissé, Gabriele, Fiebach, Jochen B, Schwab, Stefan, Schäbitz, Wolf R, Kollmar, Rainer, Fisher, Marc, Brozman, Miroslav, Skoloudik, David, Gruber, Franz, Serena Leal, Joaquin, Veltkamp, Roland, Köhrmann, Martin, Berrouschot, Jörg, AXIS 2 Investigators |
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| Přispěvatelé: | Diener, Hans Christoph (Beitragende*r) |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Advanced and Specialized Nursing
medicine.medical_specialty Neurology business.industry Medizin Filgrastim Placebo medicine.disease Surgery Granulocyte colony-stimulating factor Clinical trial Modified Rankin Scale medicine.artery Internal medicine Middle cerebral artery medicine Neurology (clinical) Cardiology and Cardiovascular Medicine business Stroke medicine.drug |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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