@article{8343449166524feb8a329e33a32a93ca,
title = "Rationale, design and critical end points for the Riluzole in Acute Spinal Cord Injury Study (RISCIS): A randomized, double-blinded, placebo-controlled parallel multi-center trial",
abstract = "Background:Riluzole is a sodium channel-blocking agent used in treating amyotrophic lateral sclerosis. It has been approved by the U.S. Food and Drug Administration, Canadian and Australian authorities, and in many other countries. A phase I trial of riluzole for acute spinal cord injury (SCI) provided safety and pharmacokinetic data and suggested neuroprotective benefits. A phase IIB/III double-blinded randomized controlled trial (RCT) started in January 2014 (https://clinicaltrials.gov, NCT01597518). This article describes the pathophysiological rationale, preclinical experience and design of the phase IIB/III RCT of Riluzole in Acute Spinal Cord Injury Study (RISCIS).Objectives:The primary objective of the trial is to evaluate the superiority of riluzole, at a dose of 100 mg BID in the first 24 h followed by 50 mg BID for the following 13 days post injury, compared with placebo in improving neurological motor outcomes in patients with C4-C8 level, International Standards for Neurological Classification of Spinal Cord Injury Examination (ISNCSCI) grade A, B or C acute (within 12 h post injury) SCI.Setting:Acute trauma centers worldwideMethods:A double-blind, multi-center, placebo-controlled RCT will enroll 351 participants randomized 1:1 to riluzole and placebo. The primary end point is the change between 180 days and baseline in ISNCSCI Motor Score. This study has 90% power to detect a change of nine points in ISNCSCI Motor Score at one-sided α=0.025.Results:Currently enrolling in 11 centers.Conclusion:This study will provide class I evidence regarding the safety and neuroprotective efficacy of riluzole in patients with acute cervical SCI.",
author = "Fehlings, {M. G.} and H. Nakashima and N. Nagoshi and Chow, {D. S.L.} and Grossman, {R. G.} and B. Kopjar",
note = "Funding Information: The investigational sites are selected from the AOSpine North America Research Network, a clinical research consortium funded by AOSpine North America, and the North American Clinical Trials Network (NACTN) for Treatment of Spinal Cord Injury sponsored by the Christopher Reeve Foundation and supported by the U. S. Department of Defense. It is planned, pending funding, that additional sites worldwide will join the study. The central trial management center is at the AOSpine Methods Core where the central electronic online data capture system is held. Dr Michael G Fehlings is the Principal Investigator and chairs the trial Steering Committee and Dr Robert G Grossman is the Co-Principal Investigator. The trial Steering Committee also consists of several content experts, a pharmacologist and a statistician. The consortium centers are listed in Table 1. All treatment sites are primary care research hospitals and clinics. Currently, 14 sites are in the United States, two are in Australia and one is in Canada. At each of these sites, there is a designated primary site investigator supported by at least one professional study coordinator, who is responsible for day-to-day operations. Before commencing enrollment, all sites received research ethics board approval and training in study operations by the AOSpine Methods Core. Funding Information: This study was financially supported by the following sources and organizations: AOspine North America; The Christopher Reeve Foundation; Telemedicine and Advanced Technology Research Center (TATRC); United States Army Medical Research and Materiel Command (USAMRMC) Award No. W81XWH-13-2-0040 EDMS 3204 and W81XWH-10-2-0042; Mission Connect (a project of the TIRR Foundation); AOSpine International Spinal Cord Injury Knowledge Forum; Halbert Chair in Neural Repair and Regeneration; and the Phillip and Peggy DeZwirek Foundation. We also wish to acknowledge funding support from the Ontario Neurotrauma Foundation and from the Rick Hansen Institute. Publisher Copyright: {\textcopyright} 2016 International Spinal Cord Society.",
year = "2016",
month = jan,
day = "1",
doi = "10.1038/sc.2015.95",
language = "English (US)",
volume = "54",
pages = "8--15",
journal = "Spinal Cord",
issn = "1362-4393",
publisher = "Nature Publishing Group",
number = "1",
}