Natalizumab in acute ischemic stroke (ACTION II): A randomized, placebo-controlled trial.

Mitchell S V Elkind Roland Veltkamp Joan Montaner S Claiborne Johnston Aneesh B Singhal Kyra Becker Maarten G Lansberg Weihua Tang Rachna Kasliwal Jacob Elkins

Neurology

From Columbia University (M.S.V.E.), New York, NY; Imperial College London (R.V.), UK; Alfried-Krupp Krankenhaus (R.V.), Essen, Germany; Vall d'Hebron Research Institute (VHIR) (J.M.), Barcelona; Institute of Biomedicine of Seville (IBiS) Stroke Programme (J.M.), Spain; University of Texas (S.C.J.), Austin; Massachusetts General Hospital (A.B.S.), Boston; University of Washington (K.B.), Seattle; Stanford University Medical Center (M.G.L.), Stanford Stroke Center, CA; and Biogen (W.T., R.K., J.E.), Cambridge, MA.

Published: August 2020

Objective: We evaluated the effect of 2 doses of natalizumab on functional outcomes in patients with acute ischemic stroke (AIS).

Methods: 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; values were not used for hypothesis testing.

Results: 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).

Conclusions: Natalizumab administered ≤24 hours after AIS did not improve patient outcomes.

Clinicaltrialsgov Identifier: 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.