Evaluating Nerinetide in Acute Ischemic Stroke: Insights from Latest Meta-Analysis

Nerinetide, delivered intravenously as a neuroprotective adjunct during endovascular thrombectomy (EVT) when IV thrombolysis is withheld, does not improve 90‑day functional outcomes. A pooled meta-analysis of randomized trials shows no benefit in functional independence or safety for nerinetide versus placebo in the EVT-only population — a null result that directly affects EVT triage and adjunctive-treatment planning.

Investigators pooled data from three randomized trials testing peri-procedural intravenous nerinetide around EVT, restricting this analysis to patients who did not receive IV thrombolysis. The EVT-only subgroup included 726 patients assigned to nerinetide and 668 to placebo. The prespecified primary endpoint was 90‑day modified Rankin Scale (mRS); the pooled estimate showed no statistically significant improvement in 90‑day mRS with nerinetide, and the aggregated data do not support a functional benefit in this clinical setting.

Safety analyses pooled adverse events, symptomatic intracranial hemorrhage, and 90‑day mortality and found no meaningful differences between nerinetide and placebo. Rates of serious adverse events and intracranial hemorrhage were numerically similar across arms, with no emergent safety signal attributable to nerinetide in the EVT-only cohorts. Thus, the absence of efficacy was not offset by a favorable safety profile.

Timing analyses examined whether earlier drug delivery changed outcomes. Some individual trials suggested a greater effect with very early administration, but the meta-analysis found inconsistent timing-related benefits across studies. Aggregate data did not confirm a reliable association between shorter onset-to-infusion intervals and improved 90‑day outcomes in the EVT-only subgroup, leaving operational timing strategies unproven.

Interpretation is tempered by methodological limits: the trials differed in design, dosing regimens, and allowable time windows, and concomitant therapies varied across centers, producing clinical and statistical heterogeneity. Patient selection varied and subgroup sample sizes were modest, limiting prespecified analyses and raising the possibility of selection and reporting biases. These constraints help explain why translating neuroprotection into consistent clinical benefit remains challenging.

Overall, current evidence indicates that nerinetide does not improve functional outcomes or change safety for patients undergoing EVT when IV thrombolysis is withheld.

Key Takeaways:

• No evidence supports routine adoption of nerinetide as peri‑EVT therapy when thrombolysis is withheld.
• Patients treated with EVT without prior IV thrombolysis should not expect a functional benefit from nerinetide outside of controlled trials.
• Future trials should standardize timing, dosing, and enrollment criteria and be prospectively powered to test very early administration and predefined subgroups.