Nelonemdaz safe but fails to improve outcomes in stroke

Treatment with nelonemdaz, a multitarget neuroprotectant that selectively blocks N-methyl-D-aspartate receptors and scavenges free radicals, does not appear to significantly improve stroke outcomes as compared with placebo, although nelonemdaz-treated patients show a greater tendency toward achieving modified Rankin Scale (mRS) scores of 0–2 at 12 weeks, according to the results of a phase II study.

The study was conducted across multiple referral stroke centres in South Korea and included 213 patients with large-artery occlusion in the anterior circulation and who received endovascular reperfusion therapy <8 hours from symptom onset. Of these, 208 patients were randomized to receive placebo (n=70), low-dose (2,750 mg) nelonemdaz (n=71), or high-dose (5,250 mg) nelonemdaz (n=67).

Treatment was administered as infusion and initiated before thrombus retrieval. Subsequent injection was given twice per day with a 12-hour interval for 5 consecutive days.

Patient characteristics at baseline were similar among the three groups, although patients in the low-dose group were younger (p=0.0426) and had more frequent use of intravenous alteplase (p=0.0331) than those in the placebo and high-dose groups. The median age of the population was 69 years, and 36.6 percent of the patients were women. The median National Institutes of Health Stroke Scale score was 15 while the median ASPECTS was 8. The rates of successful reperfusion (modified Treatment in Cerebral Ischemia score 2b–3) were 83.5 percent in the placebo group, 89.0 percent in the low-dose group, and 85.7 percent in the high-dose group (p=0.9230).

A total of 183 patients achieved the primary outcome of the proportion of patients with modified Rankin Scale scores of 0–2 at 12 weeks, with no difference across the treatment groups (54.1 percent in the placebo group, 61.5 percent in the low-dose group, and 63.2 percent in the high-dose group; p=0.5578).

Of note, both the low-dose and high-dose nelonemdaz was associated with a tendency toward a favourable shift in the mRS scores at 12 weeks compared with placebo (odds ratio, 1.55, 95 percent confidence interval [CI], 0.92–2.60 and OR, 1.61, 95 percent CI, 0.94–2.76, respectively).

There were no serious adverse events reported.