Early treatment of stroke with monosialoganglioside GM-1. Efficacy and safety results of the Early Stroke Trial.
OBJECTIVE
The Early Stroke Trial (EST) is a randomized, double-blind, placebo-controlled trial to assess the effect of monosialoganglioside GM-1 in improving recovery in patients who experienced an ischemic supratentorial stroke.


METHODS
Sixteen clinical centers recruited 805 patients, of whom 792 were confirmed to be eligible. Treatment, consisting of a first dose of either 200 mg GM-1 or placebo, was initiated within 5 hours of the onset of stroke; a second dose of either 100 mg GM-1 or placebo was administered 12 hours later. Thereafter, patients received a daily injection of 100 mg GM-1 or placebo intravenously from day 2 through 10 and intramuscularly from day 11 through 21. Patients were followed up for a total of 4 months.


RESULTS
Survival was similar in the two treatment groups. Improvement in neurological status, as measured by the change in Canadian Neurological Scale score between baseline and 4-month assessments, was greater in the group receiving GM-1; the observed difference between treatment groups was 0.22 (P = .06). A post hoc analysis in the subgroup of patients treated within 4 hours showed a statistically significant difference, with Canadian Neurological Scale mean improvement of 0.41 (P = .016). GM-1 use was not associated with differences in frequency, nature, or severity of adverse experiences.


CONCLUSIONS
These findings suggest that GM-1 is safe in the dose and treatment schedule used and that its efficacy in ischemic stroke is greater when given soon after onset of stroke.
Lenzi
G L
GL
Department of Neurological Sciences, University of Rome La Sapienza, Italy.
Grigoletto
F
F
Gent
M
M
Roberts
R S
RS
Walker
M D
MD
Easton
J D
JD
Carolei
A
A
Dorsey
F C
FC
Rocca
W A
WA
Bruno
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D005260:Female; D005677:G(M1) Ganglioside / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012449:Safety
D005677:G(M1) Ganglioside