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

M. G. Fehlings, H. Nakashima, Narihito Nagoshi, D. S L Chow, R. G. Grossman, B. Kopjar

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8-15
Number of pages8
JournalSpinal Cord
Volume54
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1

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Riluzole
Spinal Cord Injuries
Placebos
Randomized Controlled Trials
Safety
Sodium Channels
Trauma Centers
Wounds and Injuries
Amyotrophic Lateral Sclerosis
United States Food and Drug Administration
Pharmacokinetics

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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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. / Fehlings, M. G.; Nakashima, H.; Nagoshi, Narihito; Chow, D. S L; Grossman, R. G.; Kopjar, B.

In: Spinal Cord, Vol. 54, No. 1, 01.01.2016, p. 8-15.

Research output: Contribution to journalArticle

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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.",
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