Michael G Fehlings1, Jetan H Badhiwala2, Henry Ahn3, H Francis Farhadi4, Christopher I Shaffrey5, Ahmad Nassr6, Praveen Mummaneni7, Paul M Arnold8, W Bradley Jacobs9, K Daniel Riew10, Michael Kelly11, Darrel S Brodke12, Alexander R Vaccaro13, Alan S Hilibrand13, Jason Wilson14, James S Harrop15, S Tim Yoon16, Kee D Kim17, Daryl R Fourney18, Carlo Santaguida19, Eric M Massicotte2, Branko Kopjar20. 1. Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada. Electronic address: michael.fehlings@uhn.ca. 2. Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada. 3. Division of Orthopaedic Surgery, St Michael's Hospital, University of Toronto, Toronto, ON, Canada. 4. Department of Neurological Surgery, Ohio State University, Columbus, OH, USA. 5. Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA. 6. Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA. 7. Department of Neurosurgery, University of California, San Francisco, San Francisco, CA, USA. 8. Department of Neurosurgery, Kansas University Medical Center, Kansas City, KS, USA. 9. Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada. 10. Department of Orthopedic Surgery, Columbia University, New York, NY, USA. 11. Department of Orthopaedic Surgery, Washington University in St Louis, St Louis, MO, USA. 12. Department of Orthopaedics, University of Utah, Salt Lake City, UT, USA. 13. Department of Orthopaedic Surgery, Thomas Jefferson University, Rothman Orthopaedic Institute, Philadelphia, PA, USA. 14. Department of Neurosurgery, Louisiana State University, New Orleans, LA, USA. 15. Department of Neurological Surgery, Thomas Jefferson University, Philadelphia, PA, USA. 16. Department of Orthopaedics, Emory University, Atlanta, GA, USA. 17. Department of Neurological Surgery, University of California Davis, Sacramento, CA, USA. 18. Division of Neurosurgery, University of Saskatchewan, Saskatoon, SK, Canada. 19. Department of Neurology and Neurosurgery, McGill University Health Centre, Montreal, QC, Canada. 20. Department of Health Services, University of Washington, Seattle, WA, USA.
Abstract
BACKGROUND: Degenerative cervical myelopathy represents the most common form of non-traumatic spinal cord injury. This trial investigated whether riluzole enhances outcomes in patients undergoing decompression surgery for degenerative cervical myelopathy. METHODS: This multicentre, double-blind, placebo-controlled, randomised, phase 3 trial was done at 16 university-affiliated centres in Canada and the USA. Patients with moderate-to-severe degenerative cervical myelopathy aged 18-80 years, who had a modified Japanese Orthopaedic Association (mJOA) score of 8-14, were eligible. Patients were randomly assigned (1:1) to receive either oral riluzole (50 mg twice a day for 14 days before surgery and then for 28 days after surgery) or placebo. Randomisation was done using permuted blocks stratified by study site. Patients, physicians, and outcome assessors remained masked to treatment group allocation. The primary endpoint was change in mJOA score from baseline to 6 months in the intention-to-treat (ITT) population, defined as all individuals who underwent randomisation and surgical decompression. Adverse events were analysed in the modified intention-to-treat (mITT) population, defined as all patients who underwent randomisation, including those who did not ultimately undergo surgical decompression. This study is registered with ClinicalTrials.gov, NCT01257828. FINDINGS:From Jan 31, 2012, to May 16, 2017, 408 patients were screened. Of those screened, 300 were eligible (mITT population); 290 patients underwentdecompression surgery (ITT population) and received either riluzole (n=141) or placebo (n=149). There was no difference between the riluzole and placebo groups in the primary endpoint of change in mJOA score at 6-month follow-up: 2·45 points (95% CI 2·08 to 2·82 points) versus 2·83 points (2·47 to 3·19), difference -0·38 points (-0·90 to 0·13; p=0·14). The most common adverse events were neck or arm or shoulder pain, arm paraesthesia, dysphagia, and worsening of myelopathy. There were 43 serious adverse events in 33 (22%) of 147 patients in the riluzole group and 34 serious adverse events in 29 (19%) of 153 patients in the placebo group. The most frequent severe adverse events were osteoarthrosis of non-spinal joints, worsening of myelopathy, and wound complications. INTERPRETATION: In this trial, adjuvant treatment for 6 weeks perioperatively with riluzole did not improve functional recovery beyond decompressive surgery in patients with moderate-to-severe degenerative cervical myelopathy. Whether riluzole has other benefits in this patient population merits further study. FUNDING: AOSpine North America.
RCT Entities:
BACKGROUND:Degenerative cervical myelopathy represents the most common form of non-traumatic spinal cord injury. This trial investigated whether riluzole enhances outcomes in patients undergoing decompression surgery for degenerative cervical myelopathy. METHODS: This multicentre, double-blind, placebo-controlled, randomised, phase 3 trial was done at 16 university-affiliated centres in Canada and the USA. Patients with moderate-to-severe degenerative cervical myelopathy aged 18-80 years, who had a modified Japanese Orthopaedic Association (mJOA) score of 8-14, were eligible. Patients were randomly assigned (1:1) to receive either oral riluzole (50 mg twice a day for 14 days before surgery and then for 28 days after surgery) or placebo. Randomisation was done using permuted blocks stratified by study site. Patients, physicians, and outcome assessors remained masked to treatment group allocation. The primary endpoint was change in mJOA score from baseline to 6 months in the intention-to-treat (ITT) population, defined as all individuals who underwent randomisation and surgical decompression. Adverse events were analysed in the modified intention-to-treat (mITT) population, defined as all patients who underwent randomisation, including those who did not ultimately undergo surgical decompression. This study is registered with ClinicalTrials.gov, NCT01257828. FINDINGS: From Jan 31, 2012, to May 16, 2017, 408 patients were screened. Of those screened, 300 were eligible (mITT population); 290 patients underwent decompression surgery (ITT population) and received either riluzole (n=141) or placebo (n=149). There was no difference between the riluzole and placebo groups in the primary endpoint of change in mJOA score at 6-month follow-up: 2·45 points (95% CI 2·08 to 2·82 points) versus 2·83 points (2·47 to 3·19), difference -0·38 points (-0·90 to 0·13; p=0·14). The most common adverse events were neck or arm or shoulder pain, arm paraesthesia, dysphagia, and worsening of myelopathy. There were 43 serious adverse events in 33 (22%) of 147 patients in the riluzole group and 34 serious adverse events in 29 (19%) of 153 patients in the placebo group. The most frequent severe adverse events were osteoarthrosis of non-spinal joints, worsening of myelopathy, and wound complications. INTERPRETATION: In this trial, adjuvant treatment for 6 weeks perioperatively with riluzole did not improve functional recovery beyond decompressive surgery in patients with moderate-to-severe degenerative cervical myelopathy. Whether riluzole has other benefits in this patient population merits further study. FUNDING: AOSpine North America.
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