# Efficacy and safety of intravenous nerinetide in acute ischemic stroke patients undergoing endovascular thrombectomy without thrombolysis: a meta-analysis of randomized controlled trials

## TL;DR

This study found that adding nerinetide to endovascular thrombectomy in stroke patients did not improve outcomes compared to a placebo.

## Contribution

The study is the first meta-analysis evaluating nerinetide's efficacy and safety in stroke patients undergoing thrombectomy without thrombolysis.

## Key findings

- Nerinetide did not significantly improve functional outcomes in stroke patients.
- No significant differences in mortality or adverse events were observed between nerinetide and placebo groups.
- Clinical benefits of nerinetide were not observed despite preclinical support for neuroprotection.

## Abstract

This systematic review and meta-analysis aimed to evaluate the safety and efficacy of intravenous (IV) nerinetide in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) without prior or concurrent IV thrombolysis (IVT).

A systematic search of PubMed, Web of Science, and Scopus was conducted through March 15, 2025, identifying randomized controlled trials (RCTs) comparing EVT plus nerinetide versus EVT plus placebo without IVT. Screening and data extraction were performed independently by two reviewers, with conflicts resolved by a third. Risk of bias was assessed using RoB 2.0. Data were synthesized using RevMan 5.4 with random-effects models, and heterogeneity was evaluated via chi-square and I2 statistics.

Three RCTs comprising 726 patients in the IV nerinetide group and 668 in the placebo group were included. Nerinetide did not significantly improve functional outcomes: 90-day modified Rankin Scale (mRS) 0–1 (RR: 1.02, 95% CI: [0.71, 1.47], P = 0.92) and mRS 0–2 (RR: 1.07, 95% CI: [0.93, 1.22], P = 0.35). No significant differences were observed in 90-day mortality (RR: 0.89, 95% CI: [0.60, 1.34], P = 0.59) or adverse events, including symptomatic intracranial hemorrhage (RR: 0.80, 95% CI: [0.44, 1.45], P = 0.46).

Nerinetide administration during EVT in AIS patients without IVT did not significantly improve functional independence, survival, or safety outcomes compared to placebo. Although preclinical data supported neuroprotection, clinical benefits were not observed, highlighting the challenges in translating neuroprotective strategies into effective stroke therapies.

The online version contains supplementary material available at 10.1007/s00234-025-03847-z.