TY - JOUR
T1 - The Membrane-Activated Chelator Stroke Intervention (MACSI) Trial of DP-b99 in acute ischemic stroke
T2 - a randomized, double-blind, placebo-controlled, multinational pivotal Phase III study
AU - Rosenberg, Gilad
AU - Bornstein, Natan
AU - Diener, Hans Christoph
AU - Gorelick, Philip B.
AU - Shuaib, Ashfaq
AU - Lees, Kennedy
PY - 2011/8
Y1 - 2011/8
N2 - Rationale Zinc is both a direct neurotoxin and a signaling mediator in multiple early and late detrimental processes following ischemia. DP-b99, a lipophilic moderate-affinity chelator of zinc, is a first-in-class multitargeted neuroprotective agent for ischemic stroke. DP-b99 has completed several Phase I studies and two double-blind placebo-controlled Phase II trials, which supported the safety of DP-b99 and were consistent with a beneficial effect on poststroke recuperation. Aim: Membrane-Activated Chelator Stroke Intervention is a Phase III study. The primary objective is to evaluate the safety and therapeutic effects of intravenous 1·0mg/kg/day DP-b99, initiated within nine-hours of stroke onset in patients with moderately severe hemispheric acute ischemic stroke, through the analysis across the whole distribution of scores of the primary efficacy endpoint of the modified Rankin Scale, 90 days after the stroke. Methods The Membrane-Activated Chelator Stroke Intervention study is a randomized, double-blind, placebo-controlled, multicenter, multinational, parallel-arm trial comparing a placebo group to a group treated with intravenous DP-b99 for four consecutive days. Non-rtPA-treated acute ischemic stroke patients - with a baseline NIHSS score of 10-16 and a clinical syndrome that includes language dysfunction, visual field defect and/or neglect - will be stratified on a 1:1 basis to one of the two treatments. Half will be randomized within 0-4·5h of stroke onset. Follow-up after the four treatment days will occur on days 12, 30 and 90. An interim futility analysis will be performed after primary endpoint data have been collected for 50% of 770 subjects planned to be enrolled. A data and safety monitoring board will assess safety data and will oversee the interim analysis. Conclusion This Phase III Membrane-Activated Chelator Stroke Intervention trial is based on promising data derived from previous Phase I and II DP-b99 trials and capitalizes on lessons learned from failures of past stroke studies in relation to neuroprotection, patient selection and data analysis.
AB - Rationale Zinc is both a direct neurotoxin and a signaling mediator in multiple early and late detrimental processes following ischemia. DP-b99, a lipophilic moderate-affinity chelator of zinc, is a first-in-class multitargeted neuroprotective agent for ischemic stroke. DP-b99 has completed several Phase I studies and two double-blind placebo-controlled Phase II trials, which supported the safety of DP-b99 and were consistent with a beneficial effect on poststroke recuperation. Aim: Membrane-Activated Chelator Stroke Intervention is a Phase III study. The primary objective is to evaluate the safety and therapeutic effects of intravenous 1·0mg/kg/day DP-b99, initiated within nine-hours of stroke onset in patients with moderately severe hemispheric acute ischemic stroke, through the analysis across the whole distribution of scores of the primary efficacy endpoint of the modified Rankin Scale, 90 days after the stroke. Methods The Membrane-Activated Chelator Stroke Intervention study is a randomized, double-blind, placebo-controlled, multicenter, multinational, parallel-arm trial comparing a placebo group to a group treated with intravenous DP-b99 for four consecutive days. Non-rtPA-treated acute ischemic stroke patients - with a baseline NIHSS score of 10-16 and a clinical syndrome that includes language dysfunction, visual field defect and/or neglect - will be stratified on a 1:1 basis to one of the two treatments. Half will be randomized within 0-4·5h of stroke onset. Follow-up after the four treatment days will occur on days 12, 30 and 90. An interim futility analysis will be performed after primary endpoint data have been collected for 50% of 770 subjects planned to be enrolled. A data and safety monitoring board will assess safety data and will oversee the interim analysis. Conclusion This Phase III Membrane-Activated Chelator Stroke Intervention trial is based on promising data derived from previous Phase I and II DP-b99 trials and capitalizes on lessons learned from failures of past stroke studies in relation to neuroprotection, patient selection and data analysis.
KW - Acute stroke therapy
KW - Cerebral infarction
KW - Clinical trial
KW - Ischemic stroke
KW - Neuroprotection
KW - Protocols
UR - http://www.scopus.com/inward/record.url?scp=79960274195&partnerID=8YFLogxK
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U2 - 10.1111/j.1747-4949.2011.00608.x
DO - 10.1111/j.1747-4949.2011.00608.x
M3 - Article
C2 - 21645269
AN - SCOPUS:79960274195
SN - 1747-4930
VL - 6
SP - 362
EP - 367
JO - International Journal of Stroke
JF - International Journal of Stroke
IS - 4
ER -