Abstract
Introduction
There is convincing evidence from the preclinical realm that the pharmacologic agent riluzole attenuates certain aspects of the secondary injury cascade leading to diminished neurological tissue destruction in animal spinal cord injury (SCI) models. The safety and pharmacokinetic profile of riluzole has been studied in a multicenter pilot study in 36 patients. Efficacy of riluzole in acute human SCI has not been established.
Material and Methods
This phase II/III multicenter double-blind randomized controlled trial will involve up to 35 sites. A total of 351 patients with acute C4–C8 SCI and ASIA Impairment Grade A, B, or C will be randomized 1:1 to riluzole and placebo. Primary outcome is the change in ASIA Total Motor Score between baseline and 180 days. Other measures include ASIA Upper Extremity Motor Score; ASIA Lower Extremity Motor Score; ASIA Sensory Score; ASIA Grade; Spinal Cord Independence Measure; SF-36v2; EQ-5D, and GRASSP. The statistical design utilizes two-stage sequential adaptive trial. A sample size of 316 patients (158 in each arm) will have 90% power to detect 9 points difference in the ASIA Motor Score at one-sided α = 0.025. To account for losses to follow-up of up to 10%, the study will enroll 351 patients.
Results
Within the phase 1 study, a matched cohort analysis was performed comparing complication rates and neurological outcomes between patients who received riluzole and non-riluzole-treated patients from a prospective SCI registry. Although the groups experienced similar rates of complications, riluzole-treated cervical SCI patients experienced an additional 15.5 points in AMS recovery at 90 days after injury as compared with non-riluzole-treated patients. Although the phase I study was underpowered to investigate the efficacy, the current phase II/III study is poised to definitively address this question. Patient enrollment for this trial began on October 1, 2013.
Conclusion
This is a pivotal study of riluzole in acute SCI.