CONTEXT: Elucidation of the ischemic cascade has helped stimulate development of 
neuroprotective drugs aimed at limiting brain injury in the hours following an 
ischemic stroke. To date, none of these drugs has shown clinical efficacy.
OBJECTIVE: To examine the efficacy of gavestinel (GV150526), an antagonist of 
the glycine site of the N-methyl-D-aspartate receptor, as a neuroprotective 
therapy for acute ischemic stroke when administered within 6 hours of symptom 
onset.
DESIGN: The Glycine Antagonist in Neuroprotection (GAIN) Americas trial, a 
randomized, double-blind placebo-controlled trial with enrollment from April 
1998 to October 1999.
SETTING: One hundred thirty-two hospital centers across the United States and 
Canada.
PATIENTS: The primary efficacy population consisted of 1367 ischemic stroke 
patients with a predefined level of limb weakness and functional independence 
prior to stroke, stratified at randomization by age (</=75 vs >75 years) and 
initial stroke severity (National Institutes of Health [NIH] Stroke Scale scores 
of 2-5, 6-13, or >/=14).
INTERVENTION: Patients were randomly assigned to receive an intravenous loading 
dose (800 mg) plus 5 maintenance doses (200 mg every 12 hours) of gavestinel (n 
= 701) or placebo (n = 666) for 3 days.
MAIN OUTCOME MEASURE: Functional capability at 3 months, measured by the Barthel 
Index (BI), with scores trichotomized as dead/0-55, 60-90, and 95-100, compared 
between the gavestinel and placebo groups.
RESULTS: Treatment groups were well matched for baseline characteristics. For 
each group, median NIH Stroke Scale was 12, median age was 72 years, and median 
time to treatment was 5.2 hours. No statistically significant improvement on the 
3-month BI trichotomy was demonstrated for gavestinel (P =.79). The proportion 
who were functionally independent (BI score = 95-100) was 39% in the gavestinel 
group and 37% in the placebo group. No statistically significant difference in 
3-month survival was observed using Kaplan-Meier curves (P =.11). No other 
secondary end point suggested an advantage for gavestinel. Among the 333 
patients (24%) who received recombinant tissue-type plasminogen activator, there 
was also no benefit for gavestinel (P =.53). There were no serious safety 
issues.
CONCLUSION: In this study, gavestinel administered up to 6 hours after an acute 
ischemic stroke did not improve functional outcome at 3 months.