143 The Sodium-Glutamate Antagonist Riluzole Enhances Recovery After Acute Spinal Cord Injury: Re-Analysis of the RISCIS Randomized Controlled Trial Using a Global Statistical Analytic Technique

INTRODUCTION: In clinical trials, a single scale typically serves as the primary measure of intervention. However, this approach reduces the study’s power to detect the true effect of intervention, particularly in cases where outcomes exhibit high heterogeneity, and positive result varies greatly among patients. It is crucial to concurrently consider functional and quality of life measures that are often overlooked. METHODS: A total of 131 randomized patients in RISCIS were included. We used a combined assessment at six months using total AIS motor score (to measure neurological status), Spinal Cord Independence Measure (SCIM) (to measure functional status) and SF-36 PCS (to measure quality of life). A global statistical method employing the modified O’ Brien’s rank sum type test was used to compute for a global treatment effect (GTE). RESULTS: In the RISCIS trial, individual unadjusted mean difference (MD) indicates a favorable response at 6 months in the riluzole group compared to placebo across total AIS motor score [MD 2.86 (-6.79 – 12.52), p = 0.2864], SCIM [MD 6.02 (-2.47 – 14.51), p = 0.0921], and SF-36 PCS [MD 2.0 (-2.25 – 6.24), p = 0.1372]. However, none reached statistical significance on univariate testing. Interestingly, the simultaneous combined assessment of these outcome scales revealed a superior global treatment effect with riluzole versus placebo (GTE = 0.101, p = 0.0396). Overall, riluzole treatment was associated with a 55% higher probability of functional improvement compared to placebo. CONCLUSIONS: A multidimensional representation of SCI outcomes has the potential to enhance the power of estimating treatment effects of intervention. Riluzole has a global beneficial effect in acute traumatic spinal cord injury when one considers motor recovery, functional ability, and health related quality of life.