http://stroke.ahajournals.org/content/44/10/2681.abstract.html?etoc
Results of the AX200 for Ischemic Stroke Trial
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.
Another failure to use evaluation tools that are sensitive enough to detect change. The two ends of the Rankin Scale are "no symptoms" and "dead."
ReplyDelete