AXIS: a trial of intravenous granulocyte colony-stimulating factor in acute ischemic stroke.
OBJECTIVE
Granulocyte colony-stimulating factor (G-CSF) is a promising stroke drug candidate. The present phase IIa study assessed safety and tolerability over a broad dose range of G-CSF doses in acute ischemic stroke patients and explored outcome data.


METHODS
Four intravenous dose regimens (total cumulative doses of 30-180 μg/kg over the course of 3 days) of G-CSF were tested in 44 patients in a national, multicenter, randomized, placebo-controlled dose escalation study (NCT00132470; www.clinicaltrial.gov). Main inclusion criteria were a 12-hour time window after stroke onset, infarct localization to the middle cerebral artery territory, a baseline National Institutes of Health Stroke Scale range of 4 to 22, and presence of diffusion-weighted imaging/perfusion-weighted imaging mismatch.


RESULTS
Concerning the primary safety end points, we observed no increase of thromboembolic events in the active treatment groups, and no increase in related serious adverse events. G-CSF led to expected increases in neutrophils and monocytes that resolved rapidly after end of treatment. We observed a clinically insignificant drug-related decrease of platelets. As expected from the low number of patients, we did not observe significant differences in clinical outcome in treatment vs. placebo. In exploratory analyses, we observed an interesting dose-dependent beneficial effect of treatment in patients with DWI lesions > 14-17 cm³.


CONCLUSIONS
We conclude that G-CSF was well-tolerated even at high dosages in patients with acute ischemic stroke, and that a substantial increase in leukocytes appears not problematic in stroke patients. In addition, exploratory analyses suggest treatment effects in patients with larger baseline diffusion-weighted imaging lesions. The obtained data provide the basis for a second trial aimed to demonstrate safety and efficacy of G-CSF on clinical end points.
Department of Neurology, University of Münster, Münster, Germany. Wolf.Schaebitz@evkb.de
Wolf R
WR
Schäbitz
Rico
R
Laage
Gerhard
G
Vogt
Winfried
W
Koch
Rainer
R
Kollmar
Stefan
S
Schwab
Dietmar
D
Schneider
Gerhard F
GF
Hamann
Michael
M
Rosenkranz
Roland
R
Veltkamp
Jochen B
JB
Fiebach
Werner
W
Hacke
James C
JC
Grotta
Marc
M
Fisher
Armin
A
Schneider
D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005240:Feasibility Studies; D005260:Female; D005858:Germany; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007275:Injections, Intravenous; D007962:Leukocytes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016896:Treatment Outcome
D016179:Granulocyte Colony-Stimulating Factor