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).
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  This study will provide class I evidence regarding the safety and neuroprotective efficacy of riluzole in patients with acute cervical SCI.
authors.affiliation: Division of Neurosurgery and Spinal Program, Department of Surgery, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada.
authors.forename: M G
authors.initials: MG
authors.lastname: Fehlings
authors.affiliation: Division of Neurosurgery and Spinal Program, Department of Surgery, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada.|Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nakashima
authors.affiliation: Division of Neurosurgery and Spinal Program, Department of Surgery, University of Toronto, Toronto Western Hospital, Toronto, Ontario, Canada.|Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nagoshi
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX, USA.
authors.forename: D S L
authors.initials: DS
authors.lastname: Chow
authors.affiliation: Department of Neurosurgery, Houston Methodist Hospital,Houston,TX,USA.
authors.forename: R G
authors.initials: RG
authors.lastname: Grossman
authors.affiliation: Department of Health Services, University of Washington, Seattle, WA, USA.
authors.forename: B
authors.initials: B
authors.lastname: Kopjar
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019782:Riluzole / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018696:Neuroprotective Agents; D019782:Riluzole