Rationale, Design, and Early Trial Performance of AOSpine North America Multicenter Double Blind Randomized Controlled Trial of Safety and Efficacy of Riluzole in CSM (CSM—Protect Trial)

Abstract

Introduction Although surgical decompression is an effective treatment for cervical spondylotic myelopathy (CSM), many patients have substantial residual neurological and functional impairment. Compelling evidence from preclinical models suggest a benefit of adding a neuroprotective drug which targets sodium/glutamate excitotoxicity to the treatment of patients with CSM. The purpose of this study is to evaluate efficacy and safety of sodium-glutamate antagonist riluzole in improving neurological outcomes in patients with CSM undergoing surgical treatment. Patients and Methods Prospective multicenter double-blind randomized controlled trial in which a total of 300 patients undergoing surgical decompression for CSM will be randomized 1:1 to riluzole 2 × 50 mg daily for 14 days before the surgery and 28 days after the surgery or to the placebo. Primary outcome measure is change in mJOA between baseline and 6 months. Secondary outcomes include ASIA, SF36v2, NDI, Eq. 5D, Pain VAS, and complications. Sample size was estimated based on data from recently completed prospective cohort study. The sample size of 270 completed subjects will have 80% power to detect absolute difference of 0.9 in mJOA score between the investigational and the control group. The statistical analysis is organized as a sequential adaptive trial with one interim analysis at 65% of the accrued sample for early futility and efficacy. Adaptive statistical design allows for sample size adjustment at the time of interim analysis. Results To date, 153 subjects have been enrolled. Average age of the enrolled subjects is 58.4 years (SD, 10.13). The baseline mJOA is 11.9 (SD, 1.5). Baseline NDI is 42.4 (SD, 20.1) and the baseline SF36v2 Physical Component Score (PCS) is 33.5 (SD, 9.3). Conclusion In spite of the benefits of the surgical intervention, patients with CSM experience significant residual impairment and neurological compromise. Adding neuroprotective treatment with riluzole may improve outcomes of surgery. This discussion will emphasize the unique study design and the biological rationale for considering riluzole as a potential neuroprotective adjunct for patients undergoing surgery for CSM.