Lyden P, et al. - In ischemic stroke patients, researchers determined the maximally tolerated dose (MTD) of 3K3A-activated protein C (APC). To assess the MTD using tiers of 120, 240, 360, and 540 μg/kg of 3K3A-APC, researchers used a novel continual reassessment method. Patients were randomized to 1 of the 4 doses or placebo following intravenous tissue plasminogen activator, intra-arterial mechanical thrombectomy or both. One hundred ten patients were treated between January 2015 and July 2017. According to this randomized, controlled, blinded trial, the MTD was the highest-dose of 3K3A-APC tested, 540 μg/kg, with 7% as the estimated toxicity rate. No difference was found in prespecified intracranial hemorrhage (ICH) rates. 3K3A-APC reduced ICH rates from 86.5% to 67.4% in the combined treatment arms and total hemorrhage volume from an average of 2.1 ± 5.8 ml in placebo to 0.8 ± 2.1 ml in the combined treatment arms compared with placebo as seen in exploratory analyses.