Nerinetide Reduces Early Infarct Growth Among Stroke Patients Undergoing EVT Without Intravenous Alteplase

Background: Nerinetide treatment was associated with better clinical outcomes among patients with stroke undergoing endovascular treatment who were not treated with concurrent alteplase in the randomized ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke) trial. In patients receiving alteplase, no such effect was seen due to an inactivation of nerinetide by plasmin - the product of tissue plasminogen activation. We hypothesized that improved outcomes in the no-alteplase patients were associated with reduced infarct growth, a radiological correlate of improved stroke outcomes. Methods: Data are from the no-alteplase stratum of the ESCAPE-NA1 trial. Patients who underwent computer tomography perfusion (CTP) as part of routine clinical care were included. Admission CTP source data were processed using RAPID software. Infarct core at baseline was defined as areas of relative cerebral blood flow <30% on CTP. Final infarct volume was determined via manual segmentation on 24-hour CT or magnetic resonance diffusion-weighted imaging. We compared infarct growth (defined as 24-hour infarct volume minus CTP-estimated baseline infarct core) among no-alteplase patients treated with versus without nerinetide. Results: CTP maps were available in 413/1105 (37%) ESCAPE-NA1 participants. Of these, 179 (43%) were treated without alteplase, 79 (44%) received nerinetide, and 100 (56%) received placebo. Prior administration of alteplase modified the treatment effect of nerinetide on infarct growth in a multivariable model that was adjusted for age, sex, baseline infarct core volume, expanded Thrombolysis in Cerebral Infarction score, and time from baseline imaging to reperfusion (P = 0.005). In no-alteplase patients, infarct growth was larger over 24 hours in the control (34.9 mL interquartile range[IQR] [6.8-127]) versus nerinetide (19.6 mL IQR [1.7-49.1]; P = 0.008) groups. In patients who received prior alteplase (n = 234), there was no difference in infarct growth between those who received placebo versus nerinetide (10.5 mL IQR [-1.3 to 67.4] versus 12.8 mL IQR [0.35-55.5]; P = 0.62). Conclusion: Nerinetide was associated with decreased infarct growth in acute ischemic stroke patients undergoing thrombectomy without concurrent alteplase in the ESCAPE-NA1 trial.