Ignite Creation Date:
2024-05-06 @ 4:17 PM
Last Modification Date:
2024-10-26 @ 2:07 PM
Study NCT ID:
NCT04936074
Status:
RECRUITING
Last Update Posted:
2022-05-06
First Post:
2021-05-19
Brief Title:
Fusion or no Fusion After Decompression of the Spinal Cord in Patients With Degenerative Cervical Myelopathy
Sponsor:
Uppsala University Hospital
Organization:
Uppsala University Hospital
Study Overview
Official Title:
Comparison of Posterior Muscle-preserving Selective Laminectomy and Laminectomy With Fusion for Treating Degenerative Cervical Myelopathy Myelopathy Randomized Controlled Trial MyRanC
Status:
RECRUITING
Status Verified Date:
2022-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MyRanC
Brief Summary:
Background
Degenerative cervical myelopathy DCM is characterized by neck pain neck stiffness weakness paresthesia sphincter disturbance and balance disorder The mean age for symptoms is 64 years and more men than women 271 are affected The most common level is C5-C6 DCM is the predominant cause of spinal cord dysfunction in the elderly worldwide Surgical options include stand-alone laminectomy laminectomy and fusion and laminoplasty The preferable surgical approach is though a matter of controversy The objective of this study is to compare stand-alone laminectomy to laminectomy and fusion
MethodsDesign
This is a multicenter randomized controlled parallel group non-inferiority trial A total of 300 adult participants are allocated in a ratio of 11 The primary endpoint is reoperation for any reason within 5 years of follow-up Sample size and power calculations were performed by estimating the reoperation rate after laminectomy to 34 and after laminectomy with fusion to 79 based on data from the Swedish spine registry Swespine on patients with DCM
Secondary outcomes are the patient derived modified Japanese orthopaedic association P-mJOA score Neck disability index NDI European quality of life five dimensions EQ-5D Numeric rating scale NRS for neck and arm pain Hospital anxiety and depression scale HADS development of kyphosis measured as the cervical sagittal vertical axis cSVA and death Clinical and radiological follow-up is performed at 3 12 24 and 60 months after surgery The main inclusion criteria is 1-4 levels of DCM in the subaxial spine C3-C7 with or without deformity The REDcap will be used for safe data management Data will be analyzed in the per protocol PP population defined as randomized patients who are still alive without having emigrated or left the study after five years
Discussion
This will be the first randomized controlled trial comparing two of the most common surgical treatments for DCM the posterior muscle-preserving selective laminectomy and posterior laminectomy with instrumented fusion The results of the MyRanC study will provide surgical treatment recommendations for DCM This may result in improvements in surgical treatment and clinical practice regarding DCM
Degenerative cervical myelopathy DCM is characterized by neck pain neck stiffness weakness paresthesia sphincter disturbance and balance disorder The mean age for symptoms is 64 years and more men than women 271 are affected The most common level is C5-C6 DCM is the predominant cause of spinal cord dysfunction in the elderly worldwide Surgical options include stand-alone laminectomy laminectomy and fusion and laminoplasty The preferable surgical approach is though a matter of controversy The objective of this study is to compare stand-alone laminectomy to laminectomy and fusion
MethodsDesign
This is a multicenter randomized controlled parallel group non-inferiority trial A total of 300 adult participants are allocated in a ratio of 11 The primary endpoint is reoperation for any reason within 5 years of follow-up Sample size and power calculations were performed by estimating the reoperation rate after laminectomy to 34 and after laminectomy with fusion to 79 based on data from the Swedish spine registry Swespine on patients with DCM
Secondary outcomes are the patient derived modified Japanese orthopaedic association P-mJOA score Neck disability index NDI European quality of life five dimensions EQ-5D Numeric rating scale NRS for neck and arm pain Hospital anxiety and depression scale HADS development of kyphosis measured as the cervical sagittal vertical axis cSVA and death Clinical and radiological follow-up is performed at 3 12 24 and 60 months after surgery The main inclusion criteria is 1-4 levels of DCM in the subaxial spine C3-C7 with or without deformity The REDcap will be used for safe data management Data will be analyzed in the per protocol PP population defined as randomized patients who are still alive without having emigrated or left the study after five years
Discussion
This will be the first randomized controlled trial comparing two of the most common surgical treatments for DCM the posterior muscle-preserving selective laminectomy and posterior laminectomy with instrumented fusion The results of the MyRanC study will provide surgical treatment recommendations for DCM This may result in improvements in surgical treatment and clinical practice regarding DCM
Detailed Description:
Background
Degenerative cervical myelopathy DCM is characterized by neck pain and stiffness weakness and paresthesia of the extremities sphincter disturbance and bowel and balance disorder DCM is the most common cause of spinal cord dysfunction in the elderly worldwide 1 and the incidence is 41 per million within North America 2 The mean age for symptoms is 64 years of age more men than women 271 are affected and the most common level is C5-C6 3
Mechanism
DCM is typically the consequence of degenerative disc herniation osteophyte formation and hypertrophy of the ligamentum flavum that compress the spinal cord Ossification of the posterior longitudinal ligament OPLL which is more prevalent in the Asian population may also cause compression of the spinal cord
With non-operative treatments ie medication and physiotherapy 20-60 of the patients deteriorate neurologically and surgical treatment is indicated 4
Existing knowledge
The surgical treatment for DCM is decompression of the spinal cord Decompression may be achieved with an anterior or posterior approach Several algorithms have been proposed on whether to choose anterior diskectomy and fusion anterior corpectomy and fusion posterior laminectomy with fusion posterior laminoplasty or posterior laminectomy alone 56 Anterior discectomycorpectomy with fusion is recommended in patients with a straight or kyphotic spine with compression of less than three levels 6 A posterior approach is recommended in patients with cervical lordosis and compression of more than three levels 7 The WFNS Spine Committee modified these recommendations in 2019 towards a wider use of posterior approaches eg in patients with posterior compression at 1 or 2 levels and patients with a flexible kyphosis 8 It was recommended to address anterior compression with an anterior approach and posterior compression by a posterior approach Hence when propensity score matching is performed on the basis of MRI classification and description of the degenerative changes in each patient anterior andor posterior compression of the spinal cord there is no difference between anterior or posterior decompression and fusion approaches 9
Fusion is recommended in patients with DCM and concurrent signs of instability but there is no definition of instability in the degenerated cervical spine 10 In the traumatic cervical spine however instability is defined as 35 mm translation or 11 rotation on lateral flexion-extension radiographs 11 but there are no indications that degenerative changes with intact ligaments and unfractured joints would be unstable in the same way
Kyphosis of cSVA 40 mm 13 has been correlated to worse postoperative outcome normal cSVA 17-11 mm 14 Consequently the recommendation is to correct kyphosis by an anterior approach 8 but a correction does not seem to affect the outcomes 15
It remains a matter of debate among spinal surgeons whether posterior fusion after laminectomy for DCM should be mandatory or not After reports of post-laminectomy kyphosis in the 1970s and 1980s 16 prophylactic fusion has commonly been combined with the laminectomy procedure 9 In a report from 1999 34 of the patients developed kyphosis or swan neck deformity after laminectomy compared with 7 of patients surgically treated with laminoplasty using a muscle-preserving technique 17 However a muscle-preserving technique that retains the facet integrity as well as the extensor musculature may be used when performing posterior laminectomy as well and is observed to maintain sagittal balance after surgery without progression of kyphosis 18
Distal junction kyphosis DJK is a kyphotic angulation of at least 10 at the distal segment adjacent to a fused level and occurs in 24 of patients within a year after fusion surgery 19 Adjacent segment pathology ASP is progression of degeneration at the levels adjacent to a fused level and may also necessitate reoperation with decompression and extended fusion surgery 20
Considering the existence of muscle-preserving laminectomy techniques that can maintain cervical lordosis 26 there is reason to explore the additional value of instrumented fusion in the cervical spine
Although both methods are widely used they are yet to be compared in a randomized controlled study
Need for a trial
There exists a controversy among spinal surgeons regarding the need for posterior fusion when laminectomy for DCM is performed
We hypothesize that laminectomy without fusion results in shorter hospital stay and quicker return to an active life without reduced patient satisfaction functional scores or delayed kyphosis
It is important to achieve good outcome with a single surgery to spare this frail group of patients from reoperations Therefore reoperation for any reason within five years after the primary surgery will be the primary endpoint of the current study Long-term follow-up radiographs and magnetic resonance imaging MRI is needed to assess differences in the subsequent degenerative changes including spondylolisthesis kyphosis and adjacent segment pathology ASP to compare the two strategies
Additionally data from this study can be used to identify risk factors for poor outcome to guide surgical decision making
Objectives
To determine the surgical treatment associated with the lowest frequency of reoperations when treating participants with CSM by performing a non-inferiority study comparing laminectomy alone with laminectomy and fusion
To evaluate potential differences in outcome including participant satisfaction functional scores late degenerative changes including spondylolisthesis kyphosis DJK ASP and death
Study setting
Uppsala University Hospital
Karolinska University Hospital Stockholm
Ryhov Hospital Jönköping
Sahlgrenska University Hospital Gothenburg
Sample size
Based on data from the national Swedish spine registry on patients with CSM reoperation was estimated to 34 after standalone laminectomy and 79 after laminectomy and fusion Five year mortality was estimated to 163 in the same population
We further determined that excluding a 5 excess rate of reoperation in the laminectomy group vs laminectomy and fusion was a clinically relevant target for the study and therefore set the non-inferiority margin at 5 percentage points pp
With a sample size of 300 participants and with regards to mortality and an additional 5 loss due to dropout and emigration we end up with 236 analyzable patients This results in a power of 87 based on simulation using rerandomization
Recruitment
All participants diagnosed with DCM referred for surgical consultation to the orthopedic or neurosurgery departments at the participating centers will be eligible for the study Oral and written information about the study will be given at the routine physiotherapist appointment before the scheduled doctors appointment and repeated by the treating surgeon at the following consultation Participants may be enrolled if they meet the inclusion criteria and sign informed consent
Allocation
Participants will be allocated to either standalone laminectomy or laminectomy and fusion through randomization with a 11 ratio using the REDcap software Research Electronic Data Capture after informed consent and agreement to be included in the study After inserting the patients personal number into REDcap the program reports the random allocation of the patient according to the pre-constructed randomization list The randomization is stratified for center and participant sex ie using separate lists for each center and sex The allocation sequence utilizes balanced blocks of three different sizes occurring in random sequence The principal investigator and study collaborators are blinded to the sequence the block sizes and block sequence
Blinding
Trial participants will not be blinded after assignment to interventions as they have online access to their medical records by a centrally managed system
The outcome assessors and data analysts will be blinded by using a coding system for the treatment groups
Dropouts
Dropouts may be one out of two entities 1 the participant actively leaves the study or 2 the participant has died or do not show up on follow-ups for unclear reasons In case 1 the participant will not be part of the study anymore and data will not be retrieved from other information sources In case 2 information about living participants will be retrieved from the medical records radiographs and the Swedish patient registry
Statistical methods
To test for non-inferiority a two-sided 95 confidence interval CI for the difference in failure rates between the two groups will be computed To account for sparsity of events the CI will be computed using rerandomization techniques10 blocked on sex since the randomization was stratified on sex Non-inferiority will be claimed if the upper limit of the CI is less than 5 pp If non-inferiority is demonstrated superiority will also be tested using the same CI although the study is likely underpowered to detect this
All endpoints will be analyzed in the per protocol PP population defined as randomized patients who are still alive without having emigrated or left the study after five years
The secondary outcomes listed above will be analyzed using ordinal regression models adjusted for sex In addition each secondary endpoint will be dichotomized and analyzed using logistic regression The dichotomization will be done by comparing baseline and follow-up data either based on MCID when applicable or else by defining success as an improvement from baseline All secondary endpoints will be analyzed at 1 2 and 5 years of follow-up but not until the study is closed and the primary results is published
The study statistician is Lars Lindhagen at Uppsala Clinical Research Center
Data collection
Questionnaires including baseline questionnaires and postal follow-up questionnaires as well as validated PROMs will be distributed the participants preoperatively Postoperatively the participants are routinely followed via the Swespine swespinese and follow-up questionnaires and PROMS will be retrieved from Swespine414950
Closing statement
Degenerative cervical myelopathy is the most common cause of spinal cord dysfunction in the elderly worldwide and the incidence is 41 per million within North America Until now there is no consensus whether to fuse or not when laminectomy is performed and the choice of surgical method is mainly up to the surgeons preference
This will be the first randomized controlled trial comparing two of the most common surgical treatments for DCM the posterior muscle-preserving selective laminectomy and posterior laminectomy with instrumented fusion
Degenerative cervical myelopathy DCM is characterized by neck pain and stiffness weakness and paresthesia of the extremities sphincter disturbance and bowel and balance disorder DCM is the most common cause of spinal cord dysfunction in the elderly worldwide 1 and the incidence is 41 per million within North America 2 The mean age for symptoms is 64 years of age more men than women 271 are affected and the most common level is C5-C6 3
Mechanism
DCM is typically the consequence of degenerative disc herniation osteophyte formation and hypertrophy of the ligamentum flavum that compress the spinal cord Ossification of the posterior longitudinal ligament OPLL which is more prevalent in the Asian population may also cause compression of the spinal cord
With non-operative treatments ie medication and physiotherapy 20-60 of the patients deteriorate neurologically and surgical treatment is indicated 4
Existing knowledge
The surgical treatment for DCM is decompression of the spinal cord Decompression may be achieved with an anterior or posterior approach Several algorithms have been proposed on whether to choose anterior diskectomy and fusion anterior corpectomy and fusion posterior laminectomy with fusion posterior laminoplasty or posterior laminectomy alone 56 Anterior discectomycorpectomy with fusion is recommended in patients with a straight or kyphotic spine with compression of less than three levels 6 A posterior approach is recommended in patients with cervical lordosis and compression of more than three levels 7 The WFNS Spine Committee modified these recommendations in 2019 towards a wider use of posterior approaches eg in patients with posterior compression at 1 or 2 levels and patients with a flexible kyphosis 8 It was recommended to address anterior compression with an anterior approach and posterior compression by a posterior approach Hence when propensity score matching is performed on the basis of MRI classification and description of the degenerative changes in each patient anterior andor posterior compression of the spinal cord there is no difference between anterior or posterior decompression and fusion approaches 9
Fusion is recommended in patients with DCM and concurrent signs of instability but there is no definition of instability in the degenerated cervical spine 10 In the traumatic cervical spine however instability is defined as 35 mm translation or 11 rotation on lateral flexion-extension radiographs 11 but there are no indications that degenerative changes with intact ligaments and unfractured joints would be unstable in the same way
Kyphosis of cSVA 40 mm 13 has been correlated to worse postoperative outcome normal cSVA 17-11 mm 14 Consequently the recommendation is to correct kyphosis by an anterior approach 8 but a correction does not seem to affect the outcomes 15
It remains a matter of debate among spinal surgeons whether posterior fusion after laminectomy for DCM should be mandatory or not After reports of post-laminectomy kyphosis in the 1970s and 1980s 16 prophylactic fusion has commonly been combined with the laminectomy procedure 9 In a report from 1999 34 of the patients developed kyphosis or swan neck deformity after laminectomy compared with 7 of patients surgically treated with laminoplasty using a muscle-preserving technique 17 However a muscle-preserving technique that retains the facet integrity as well as the extensor musculature may be used when performing posterior laminectomy as well and is observed to maintain sagittal balance after surgery without progression of kyphosis 18
Distal junction kyphosis DJK is a kyphotic angulation of at least 10 at the distal segment adjacent to a fused level and occurs in 24 of patients within a year after fusion surgery 19 Adjacent segment pathology ASP is progression of degeneration at the levels adjacent to a fused level and may also necessitate reoperation with decompression and extended fusion surgery 20
Considering the existence of muscle-preserving laminectomy techniques that can maintain cervical lordosis 26 there is reason to explore the additional value of instrumented fusion in the cervical spine
Although both methods are widely used they are yet to be compared in a randomized controlled study
Need for a trial
There exists a controversy among spinal surgeons regarding the need for posterior fusion when laminectomy for DCM is performed
We hypothesize that laminectomy without fusion results in shorter hospital stay and quicker return to an active life without reduced patient satisfaction functional scores or delayed kyphosis
It is important to achieve good outcome with a single surgery to spare this frail group of patients from reoperations Therefore reoperation for any reason within five years after the primary surgery will be the primary endpoint of the current study Long-term follow-up radiographs and magnetic resonance imaging MRI is needed to assess differences in the subsequent degenerative changes including spondylolisthesis kyphosis and adjacent segment pathology ASP to compare the two strategies
Additionally data from this study can be used to identify risk factors for poor outcome to guide surgical decision making
Objectives
To determine the surgical treatment associated with the lowest frequency of reoperations when treating participants with CSM by performing a non-inferiority study comparing laminectomy alone with laminectomy and fusion
To evaluate potential differences in outcome including participant satisfaction functional scores late degenerative changes including spondylolisthesis kyphosis DJK ASP and death
Study setting
Uppsala University Hospital
Karolinska University Hospital Stockholm
Ryhov Hospital Jönköping
Sahlgrenska University Hospital Gothenburg
Sample size
Based on data from the national Swedish spine registry on patients with CSM reoperation was estimated to 34 after standalone laminectomy and 79 after laminectomy and fusion Five year mortality was estimated to 163 in the same population
We further determined that excluding a 5 excess rate of reoperation in the laminectomy group vs laminectomy and fusion was a clinically relevant target for the study and therefore set the non-inferiority margin at 5 percentage points pp
With a sample size of 300 participants and with regards to mortality and an additional 5 loss due to dropout and emigration we end up with 236 analyzable patients This results in a power of 87 based on simulation using rerandomization
Recruitment
All participants diagnosed with DCM referred for surgical consultation to the orthopedic or neurosurgery departments at the participating centers will be eligible for the study Oral and written information about the study will be given at the routine physiotherapist appointment before the scheduled doctors appointment and repeated by the treating surgeon at the following consultation Participants may be enrolled if they meet the inclusion criteria and sign informed consent
Allocation
Participants will be allocated to either standalone laminectomy or laminectomy and fusion through randomization with a 11 ratio using the REDcap software Research Electronic Data Capture after informed consent and agreement to be included in the study After inserting the patients personal number into REDcap the program reports the random allocation of the patient according to the pre-constructed randomization list The randomization is stratified for center and participant sex ie using separate lists for each center and sex The allocation sequence utilizes balanced blocks of three different sizes occurring in random sequence The principal investigator and study collaborators are blinded to the sequence the block sizes and block sequence
Blinding
Trial participants will not be blinded after assignment to interventions as they have online access to their medical records by a centrally managed system
The outcome assessors and data analysts will be blinded by using a coding system for the treatment groups
Dropouts
Dropouts may be one out of two entities 1 the participant actively leaves the study or 2 the participant has died or do not show up on follow-ups for unclear reasons In case 1 the participant will not be part of the study anymore and data will not be retrieved from other information sources In case 2 information about living participants will be retrieved from the medical records radiographs and the Swedish patient registry
Statistical methods
To test for non-inferiority a two-sided 95 confidence interval CI for the difference in failure rates between the two groups will be computed To account for sparsity of events the CI will be computed using rerandomization techniques10 blocked on sex since the randomization was stratified on sex Non-inferiority will be claimed if the upper limit of the CI is less than 5 pp If non-inferiority is demonstrated superiority will also be tested using the same CI although the study is likely underpowered to detect this
All endpoints will be analyzed in the per protocol PP population defined as randomized patients who are still alive without having emigrated or left the study after five years
The secondary outcomes listed above will be analyzed using ordinal regression models adjusted for sex In addition each secondary endpoint will be dichotomized and analyzed using logistic regression The dichotomization will be done by comparing baseline and follow-up data either based on MCID when applicable or else by defining success as an improvement from baseline All secondary endpoints will be analyzed at 1 2 and 5 years of follow-up but not until the study is closed and the primary results is published
The study statistician is Lars Lindhagen at Uppsala Clinical Research Center
Data collection
Questionnaires including baseline questionnaires and postal follow-up questionnaires as well as validated PROMs will be distributed the participants preoperatively Postoperatively the participants are routinely followed via the Swespine swespinese and follow-up questionnaires and PROMS will be retrieved from Swespine414950
Closing statement
Degenerative cervical myelopathy is the most common cause of spinal cord dysfunction in the elderly worldwide and the incidence is 41 per million within North America Until now there is no consensus whether to fuse or not when laminectomy is performed and the choice of surgical method is mainly up to the surgeons preference
This will be the first randomized controlled trial comparing two of the most common surgical treatments for DCM the posterior muscle-preserving selective laminectomy and posterior laminectomy with instrumented fusion
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None