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 ofintravenous 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 (mean+/-SD) 12.2+/-4.0 and 12.6+/-3.3, respectively; the time to needle (mean+/-SD) was 6:36+/-1:47 and 6:28+/-1:33 hours, respectively; and the age (mean+/-SD) was 73.3+/-9.9 and 72.0+/-9.6 years, respectively. The 90-day median change from baseline (the primary end point) was -6.0 and -5.0 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 (P=0.05). 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 (P=0.03). 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.
RCT Entities:
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 strokepatients 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 (mean+/-SD) 12.2+/-4.0 and 12.6+/-3.3, respectively; the time to needle (mean+/-SD) was 6:36+/-1:47 and 6:28+/-1:33 hours, respectively; and the age (mean+/-SD) was 73.3+/-9.9 and 72.0+/-9.6 years, respectively. The 90-day median change from baseline (the primary end point) was -6.0 and -5.0 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 (P=0.05). 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 (P=0.03). 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.
Authors: Ashfaq Shuaib; Stefan Schwab; J Neal Rutledge; Sidney Starkman; David S Liebeskind; Gary L Bernardini; Alan Boulos; Alex Abou-Chebl; David Y Huang; Geert Vanhooren; Salvador Cruz-Flores; Richard Paul Klucznik; Jeffrey L Saver Journal: J Neurointerv Surg Date: 2013-01-03 Impact factor: 5.836
Authors: Dennis J Grab; Elizabeth Nenortas; Rahul P Bakshi; Olga V Nikolskaia; Jonathan E Friedman; Theresa A Shapiro Journal: Parasitol Int Date: 2013-06-28 Impact factor: 2.230