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

Spinal Cord. 2016 Jan;54(1):8-15. doi: 10.1038/sc.2015.95. Epub 2015 Jun 23.


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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neuroprotective Agents / therapeutic use*
  • Riluzole / therapeutic use*
  • Severity of Illness Index
  • Spinal Cord Injuries / drug therapy*
  • Time Factors
  • Treatment Outcome
  • Young Adult


  • Neuroprotective Agents
  • Riluzole

Associated data

  • ClinicalTrials.gov/NCT01597518