The Neuroprotection with Statin Therapy for Acute Recovery Trial (NeuSTART): an adaptive design phase I dose-escalation study of high-dose lovastatin in acute ischemic stroke.

International Journal of Stroke : Official Journal of the International Stroke Society
Mitchell S V ElkindKen Cheung

Abstract

There is growing experimental and clinical evidence that by reducing downstream products of the mevalonate pathway other than cholesterol, HMG-CoA reductase inhibitors ('statins') have beneficial effects on endothelial function, coronary and cerebral blood flow, inflammation, and hemostasis. Statins have been shown in rodent models of acute ischemic stroke to reduce neuronal injury and infarct size in a dose-dependent fashion. The objective of this early phase trial will be to determine the maximal-tolerated dose of lovastatin for short-term acute stroke therapy. In this multicenter phase 1B dose-escalation and dose-finding study, 33 patients with acute ischemic stroke will be administered lovastatin in increasing doses from one to 10 mg/kg daily for 3 days beginning within 24 hours after symptom onset. The primary safety outcome will be occurrence of myotoxicity or hepatotoxicity, defined by clinical and laboratory criteria, and the study is designed to determine the highest dose of lovastatin that can be administered with <10% risk of myotoxicity or hepatotoxicity. The statistical design of the study utilizes an adaptive design, the Continual Reassessment Method, which is novel to stroke trials, to find the optimal dosage. Th...Continue Reading

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Citations

Feb 5, 2010·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Elissa F Wible, Daniel T Laskowitz
Mar 1, 2010·Biometrika·Ying Kuen Cheung, Mitchell S V Elkind
Sep 3, 2011·Stroke; a Journal of Cerebral Circulation·Ken Cheung, Petra Kaufmann
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Feb 6, 2017·Circulation Research·Amelia K BoehmeMitchell S V Elkind
Oct 10, 2015·Stroke; a Journal of Cerebral Circulation·Shadi Yaghi, Mitchell S V Elkind
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Jan 4, 2017·European Journal of Dentistry·Soukaina RyalatFaleh Sawair
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Jun 21, 2019·Current Medicinal Chemistry·Konstantinos AznaouridisDimitris Tousoulis
Nov 27, 2020·Drug Delivery·Qiong WuJingjing Sun

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Software Mentioned

– CRM
NeuSTART
SPARCL
TITE

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