Complete recanalization up to 24 hours after stroke onset is significantly associated with the short-term clinical course and functional outcome 30 days after acute stroke.

Disturbance in metallochemical reactions and metal‐protein association are associated with chronic neurodegenerative conditions, such as Alzheimer's and Parkinson's disease, as well as with neurodegeneration triggered by acute cerebral ischaemia. Many neurological diseases have been linked directly or indirectly to perturbed homeostasis of Ca, Fe, Zn, or Cu ions. Consequently, acute or chronic neurodegenerative disorders represent excellent targets for exploiting metal ion chelator approaches. Drug Dev. Res. 56: 300–309, 2002. © 2002 Wiley‐Liss, Inc.

Background and Purpose-DP-b99 is a chelator of zinc and calcium ions that acts selectively within cell membranes and has neuroprotective properties in animal models of stroke. We present the results of a multicenter, double-blind, placebo-controlled, randomized trial to assess the safety and potential protective effects of DP-b99 in acute ischemic stroke. Methods-One hundred and fifty stroke patients with signs of cortical involvement and a National Institutes of Health Stroke Scale (NIHSS) score of 7 to 20 received a 4-day course of intravenous 1 mg/kg per day DP-b99 or placebo within 1 to 9 hours of stroke onset. Treatment with recombinant tissue plasminogen activator was not allowed. Results-No major differences in mortality rate, causes of death, adverse events, safety laboratory tests, and ECG parameters were found between the 2 groups. The baseline NIHSS score of the 72 DP-b99 -and 75 placebo-treated patients in the intent-to-treat cohort was (meanϮSD) 12.2Ϯ4.0 and 12.6Ϯ3.3, respectively; the time to needle (meanϮSD) was 6:36Ϯ1:47 and 6:28Ϯ1:33 hours, respectively; and the age (meanϮSD) was 73.3Ϯ9.9 and 72.0Ϯ9.6 years, respectively. The 90-day median change from baseline (the primary end point) was Ϫ6.0 and Ϫ5.0 NIHSS points in the DP-b99 and placebo groups, respectively (nonsignificant). At 90 days, there was a significantly better outcome in the DP-b99 group compared with the placebo group (modified Rankin scale score of 0, 1, or same as prestroke): 30.6% and 16.0%, respectively (Pϭ0.05). The recovery rate was unaffected by the time to needle. Further analyses indicated that the 90-day median change from baseline in patients with an entry NIHSS score of 10 to 16 was 8.0 and 5.0 points in the DP-b99 and placebo groups, respectively (Pϭ0.03). Conclusions-In this small-scale study, the primary end point of change in NIHSS score from baseline to 90 days was not met. However, secondary end points demonstrated a significantly improved 90-day recovery rate with treatment with DP-b99 when compared with placebo. In addition, in patients with baseline NIHSS scores of 10 to 16, a significant post hoc change in NIHSS score from baseline to day 90 was observed. No major safety problems were identified. These findings need to be confirmed with a larger prospective study of strokes involving the cortex. (Stroke. 2008; 39:1774-1778.)