TY - JOUR
T1 - Safety and efficacy of riluzole in patients undergoing decompressive surgery for degenerative cervical myelopathy (CSM-Protect)
T2 - a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial
AU - Fehlings, Michael G.
AU - Badhiwala, Jetan H.
AU - Ahn, Henry
AU - Farhadi, H. Francis
AU - Shaffrey, Christopher I.
AU - Nassr, Ahmad
AU - Mummaneni, Praveen
AU - Arnold, Paul M.
AU - Jacobs, W. Bradley
AU - Riew, K. Daniel
AU - Kelly, Michael
AU - Brodke, Darrel S.
AU - Vaccaro, Alexander R.
AU - Hilibrand, Alan S.
AU - Wilson, Jason
AU - Harrop, James S.
AU - Yoon, S. Tim
AU - Kim, Kee D.
AU - Fourney, Daryl R.
AU - Santaguida, Carlo
AU - Massicotte, Eric M.
AU - Kopjar, Branko
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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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U2 - 10.1016/S1474-4422(20)30407-5
DO - 10.1016/S1474-4422(20)30407-5
M3 - Article
C2 - 33357512
AN - SCOPUS:85099175013
SN - 1474-4422
VL - 20
SP - 98
EP - 106
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 2
ER -