Shuya Li, MD; Baoyu Feng, PhD; Dandan He, PhD; Xuechun Wang, PhD; Hao Li, PhD; Shuhong Xu, PhD; Hong-Qiu Gu, PhD;
Xiaohua Xiao, MD; Dan Deng, MD; Xiaoli Wang, MD; Aihong Guo, MD; Hongguo Dai, MD; Zixiao Li, MD; Yilong Wang, MD;
Xingquan Zhao, MD; Liping Liu, MD; Yongjun Wang, MD; for the LAIS investigators
IMPORTANCE Effective neuroprotective and neuroreparative therapies for acute ischemic
stroke remain limited. Loberamisal is a small-molecule compound that dually targets the
postsynaptic density 95 (PSD-95) pathway and α2 γ-aminobutyric acid type α (α2-GABAA)
receptor.
OBJECTIVE To evaluate the efficacy and safety of intravenous loberamisal for improving
functional outcomes in patients with acute ischemic stroke.
DESIGN, SETTING, AND PARTICIPANTS The Loberamisal for Acute Ischemic Stroke (LAIS) trial
was a multicenter, double-blind, randomized, placebo-controlled phase 3 clinical trial
conducted at 32 hospitals in China. Adults aged 18 to 80 years with acute ischemic stroke, a
baseline National Institutes of Health Stroke Scale score of 7 to 20, and no prestroke disability
(modified Rankin Scale score, 1) who presented within 48 hours of symptom onset were
enrolled between July 24, 2024, and December 7, 2024, with final follow-up on April 8, 2025.
INTERVENTIONS Participants were randomly assigned (1:1) to receive intravenous loberamisal
(40 mg) or matching placebo once daily for 10 consecutive days, in addition to standard
stroke care.
MAIN OUTCOMES AND MEASURES The primary outcome was achieving a full functional
outcome at 90 days, defined as a modified Rankin Scale (mRS) score of 0 to 1. Safety
outcomes included adverse events, serious adverse events, and mortality.
RESULTS Among 998 randomized participants, 997 received at least 1 dose of the study drug
and were included in the primary analysis (502 in the loberamisal group and 495 in the
placebo group). The median age was 64 years (IQR, 57-71), 336 participants (33.7%) were
women, and the median baseline NIHSS score was 8 (IQR, 7-9). At 90 days, 350 participants
(69.7%) in the loberamisal group achieved an mRS score of 0 to 1 compared with 279 (56.3%)
in the placebo group (relative risk, 1.24; 95% CI, 1.12-1.36; risk difference, 13.28%; 95% CI,
7.24%-19.32%). Adverse events occurred in 441 participants (87.8%) in the loberamisal group
and 439 (88.7%) in the placebo group. Serious adverse events occurred in 43 participants
(8.6%) in the loberamisal group and 53 (10.7%) in the placebo group. All-cause mortality
occurred in 6 participants (1.2%) in the loberamisal group and 10 (2.0%) in the placebo group.
CONCLUSIONS AND RELEVANCE Among patients with acute ischemic stroke treated within
48 hours of symptom onset, intravenous loberamisal, compared with placebo, resulted
in a higher proportion of patients achieving full functional outcomes at 90 days. Further
studies are needed to validate these findings and establish whether the benefits could extend
to a broader patient population.
