Gavestinel does not improve outcome after acute intracerebral hemorrhage: an analysis from the GAIN International and GAIN Americas studies.
OBJECTIVE
Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas trials were prospectively designed, randomized, placebo-controlled trials of gavestinel, a glycine-site antagonist and putative neuroprotectant drug administered within 6 hours of suspected ischemic or hemorrhagic stroke. Both trials reported that gavestinel was ineffective in ischemic stroke. This analysis reports the results in those with primary intracerebral hemorrhage.


METHODS
The primary hypothesis was that gavestinel treatment did not alter outcome, measured at 3 months by the Barthel Index (BI), from acute intracerebral hemorrhage, based on pooled results from both trials. The BI scores were divided into 3 groups: 95 to 100 (independent), 60 to 90 (assisted independence), and 0 to 55 (dependent) or dead.


RESULTS
In total, 3450 patients were randomized in GAIN International (N=1804) and GAIN Americas (N=1646). Of these, 571 were ultimately identified to have spontaneous intracerebral hematoma on baseline head computerized tomography scan. The difference in distribution of trichotomized BI scores at 3 months between gavestinel and placebo was not statistically significant (P=0.09). Serious adverse events were reported at similar rates in the 2 treatment groups.


CONCLUSIONS
These observations from the combined GAIN International and GAIN Americas trials suggest that gavestinel is not of substantial benefit or harm to patients with primary intracerebral hemorrhage. These findings are similar to results previously reported in patients with ischemic stroke.
Haley
E Clarke
EC
Department of Neurology, University of Virginia Health System, Charlottesville, VA 22901, USA. ech@virginia.edu
Thompson
John L P
JL
Levin
Bruce
B
Davis
Stephen
S
Lees
Kennedy R
KR
Pittman
John G
JG
DeRosa
Janet T
JT
Ordronneau
Paul
P
Brown
Devin L
DL
Sacco
Ralph L
RL
D000208:Acute Disease; D000368:Aged; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D018684:Glycine Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D020521:Stroke / Q000188:drug therapy; D017211:Treatment Failure; D014481:United States
C105319:3-(2-((phenylamino)carbonyl)ethenyl)-4,6-dichloroindole-2-carboxylic acid; D018684:Glycine Agents; D007211:Indoles