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Background and Purpose— DP-b99, a lipophilic moderate-affinity chelator of zinc, was postulated to improve recovery after acute ischemic stroke. We evaluated the safety and therapeutic effects of DP-b99 in patients with acute hemispheric ischemic stroke. Methods— The Membrane-Activated Chelator Stroke Intervention trial was a randomized, double-blind, placebo-controlled, multicenter, parallel-group trial of intravenous DP-b99 administered for 4 consecutive days (NCT00893867). Acute ischemic stroke patients within 9 hours of onset, but untreated by alteplase, with a baseline National Institutes of Health Stroke Scale score of 10 to 16, and evidence of language dysfunction, visual field defect, and neglect were eligible. The primary efficacy analysis compared distributions of functional status measured by modified Rankin score in the intent-to-treat population of patients with any post-treatment outcome, adjusted for initial severity. Functional and neurological recovery were secondary measures. Home time was an exploratory end point. Results— Enrollment terminated at n=446 after the planned interim analysis determined futility; follow-up continued. Final modified Rankin score distributions were equal between DP-b99 and placebo-treated groups ( P =0.10; P adj adjusted for baseline age and National Institutes of Health Stroke Scale=0.21). Fewer patients recovered to modified Rankin score ≤1 in the DP-b99–treated group (45/218; 20.6%) than after placebo (63/219; 28.8%) ( P =0.05; P adj =0.10). Similarly, fewer patients attained National Institutes of Health Stroke Scale ≤1 after DP-b99 (42/218; 19.3%) than placebo (56/219; 25.6%; P =0.10; P adj =0.26). Mortality was similar between DP-b99 and placebo intent-to-treat groups (36/218; 16.5% vs 33/219; 15.1%; P =0.68). Home time was unchanged by treatment (median 36 vs 36.5 days; P =0.25). Conclusions— Despite encouraging preclinical and phase II trial data, DP-b99 shows no evidence of efficacy in treating human ischemic stroke.

Individuals who cannot functionally reposition themselves often need dynamic seating interventions that change body posture from automatic chair adjustments. Pelvis alignment directly affects sitting posture, and systems that adjust and monitor pelvis angle simultaneously might be applicable to control body posture in sitting. The present study explores whether it is feasible to monitor pelvis angle from seat support forces. Pelvis angle estimation was based on equivalent “two-force member” loading for which pelvis orientation equals the orientation of the equivalent contact force. Theoretical evaluation was done to derive important conditions for practical application. An instrumented wheelchair was developed for experimental validation in healthy subjects. Seat support forces were measured, and mechanical analysis was done to derive the equivalent contact force from which we estimated the pelvis angle. Model analysis showed a significant influence of pelvis mass, hip force, and lumbar torque on the relation between the actual pelvis angle and the predicted pelvis angle. Proper force compensation and minimal lumbar torque seemed important for accurate pelvis angle estimations. Experimental evaluation showed no body postures that involved a clear relation between the pelvis angle and the orientation of the equivalent contact force. Findings suggest that pelvis angle could not be estimated in healthy individuals under the described experimental seating conditions. Validation experiments with impaired individuals must be performed under different seating conditions to provide a better understanding whether the principle is of interest for clinical application.