Elkind, Mitchell S VVeltkamp, RolandMontaner, JoanJohnston, S ClaiborneSinghal, Aneesh BBecker, KyraLansberg, Maarten GTang, WeihuaKasliwal, RachnaElkins, Jacob2023-02-092023-02-092020-06-26http://hdl.handle.net/10668/15837We evaluated the effect of 2 doses of natalizumab on functional outcomes in patients with acute ischemic stroke (AIS). In this double-blind phase 2b trial, patients with AIS aged 18-80 years with NIH Stroke Scale scores of 5-23 from 53 US and European sites were randomized 1:1:1 to receive a single dose of 300 or 600 mg IV natalizumab or placebo, with randomization stratified by treatment window (≤9 or >9 to ≤24 hours from patient's last known normal state). The primary endpoint was a composite measure of excellent outcome (modified Rankin Scale score ≤1 and Barthel Index score ≥95) at day 90 assessed in all patients receiving a full dose. Sample size was estimated from a Bayesian model; p values were not used for hypothesis testing. An excellent outcome was less likely with natalizumab than with placebo (natalizumab 300 or 600 mg odds ratio 0.60; 95% confidence interval 0.39-0.93). There was no effect modification by time to treatment or use of thrombolysis/thrombectomy. For natalizumab 300 mg, 600 mg, or placebo, there were no differences in incidence of adverse events (90.0%, 92.1%, and 92.3%, respectively), serious adverse events (25.6%, 32.6%, and 20.9%, respectively), or deaths (6.7%, 4.5%, and 5.5%, respectively). Natalizumab administered ≤24 hours after AIS did not improve patient outcomes. NCT02730455 CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with AIS, an excellent outcome was less likely in patients treated with natalizumab than with placebo.enAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/AgedBrain IschemiaDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansImmunologic FactorsMaleMiddle AgedNatalizumabRecovery of FunctionStrokeresearch article32591475open access10.1212/WNL.00000000000100381526-632XPMC7668547https://n.neurology.org/content/neurology/95/8/e1091.full.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668547/pdf