BACKGROUND AND PURPOSE: Gavestinel, GV150526, is a selective antagonist at the 
glycine site of the N-methyl-D-aspartate receptor. The safety and efficacy of 
GV150526 were studied in two phase III randomized placebo-controlled clinical 
trials of acute ischemic stroke patients within 6 h from onset [The Glycine 
Antagonist in Neuroprotection (GAIN) International and GAIN Americas Trials]. A 
planned MRI substudy within these trials investigated the effect of gavestinel 
on infarct volume.
METHODS: Patients enrolled in the GAIN trials at designated MRI substudy sites 
were eligible if they had a pretreatment acute cortical lesion on 
diffusion-weighted MRI of at least 1.5 cm diameter or 5 cm(3). Final lesion 
assessment was performed on T(2)-weighted MRI at month 3. Blinded image analysis 
was performed centrally. The primary hypothesis was that gavestinel would 
attenuate lesion growth from baseline relative to placebo.
RESULTS: A total of 106 patients were eligible, 75 (34 gavestinel, 41 placebo) 
of whom had month 3 scans (primary analysis population). No effects of 
gavestinel on infarct volume were observed in the primary or other analyses. 
However, significant associations of lesion volume to clinical severity and 
outcomes were observed. Ischemic lesion volume decrease was predictive of 
substantial clinical improvement.
CONCLUSION: Consistent with the clinical outcomes in the GAIN trials, no effects 
of gavestinel on ischemic infarction was observed. Concordance of results of the 
clinical outcome trials with those of this infarct volume substudy as well the 
associations of infarct volume to clinical outcomes further support the 
potential role of infarct volume as a marker of outcome in dose finding and 
proof of principle acute stroke trials.