Clinical trial NCT00506558: The CSM Trial: A Multicenter Study Comparing Ventral to Dorsal Surgery for Cervical Spondylotic Myelopathy
Official title: The CSM Trial: A Multicenter Study Comparing Ventral to Dorsal Surgery for Cervical Spondylotic Myelopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cervical Spondylotic Myelopathy
Keywords: cervical spondylotic myelopathy
degenerative cervical spondylosis
spinal fusion
Lead sponsor: Greenwich Hospital
Sponsor class: OTHER
Collaborators: name: Yale University
First posted: 2007-07-25
Enrollment: 103
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine the optimal surgical approach (ventral versus dorsal) for patients with multi-level cervical spondylotic myelopathy (CSM). There are no established guidelines for the management of patients with CSM, which slowly causes spinal cord injury in afflicted patients.

This study aims to test the hypothesis that ventral surgery (decompressing the spinal cord from the front of the neck) and dorsal surgery (decompressing the spinal cord from the back of the neck) might differ in their overall outcome or major complication rate.

Detailed description: A. Purpose To determine the optimal surgical approach (ventral versus dorsal) for patients with multi-level cervical spondylotic myelopathy (CSM).

B. Background There are no established guidelines for the management of patients with CSM. It is estimated that up to 30 percent of patients have an unsatisfactory outcome after surgery for CSM. It remains uncertain how dorsal and ventral approaches differ in their success rates and in their complication rates. This study aims to test the hypothesis that ventral and dorsal surgical approaches differ in their outcomes or major complication rates. A secondary hypothesis is that fusion might improve outcome by reducing repetitive shear injury to the spinal cord.

C. Specific Location of Study

This is a multi-center trial. Subjects will be entered into the study from 9 separate centers. At this site, subjects will be recruited from the office of Dr. Zoher Ghogawala. All subjects at this site will undergo surgery at Greenwich Hospital.

D. Probable Duration of Project

Subjects will be recruited into the study for one year. All subjects will be followed for 1 year.

E. Research Plan

1. Prospective, non-randomized multicenter trial. Approximately 100-200 patients would be recruited over one year with follow-up at one year.
2. Subjects (aged 40-85 years) with spinal cord compression (2 or more levels) from degenerative cervical spondylosis with clinical myelopathy will be treated with either ventral decompression/fusion or dorsal decompression with or without fusion.
3. Subjects with cervical kyphosis \> 5˚, a segmental kyphotic deformity defined as 3 or more disc-osteophytes that extend dorsal to a line drawn from the dorsal caudal point of C2 to the dorsal caudal point of C7, ossification of the posterior longitudinal ligament (OPLL), or developmental spinal canal narrowing (12mm) would be excluded from the study.
4. Functional outcomes will be determined using well-known quantitative scales (SF-36, Oswestry Neck, mJOA, Nurick, and EuroQol-5D). These instruments will be administered pre-op, 3 months, 6 months, and 1 year post-op.
5. Two independent neuroradiologists will review the initial films to confirm eligibility and review post-operative films (3 months, 6 months, and 1 year) to determine radiographic decompression and fusion as well as any complications.
6. An independent study coordinator will collect data at 30 days and at 1 year to document any complications or re-operations.

F. Data and Safety Monitoring Plan

1. All serious unexpected adverse events (e.g. death within 30 days of operation) will be reported to the IRB within 24 hours. Any appropriate funding agencies or regulatory agencies would be notified as well.
2. Any serious anticipated adverse event (e.g. wound infection, pulmonary embolus) will be reported to the IRB whenever their magnitude or frequency exceeds expectations.
3. All other adverse events (including loss of privacy, significant economic harm) will be reported to the IRB on an annual basis or at the time that re-approval is sought. Any adverse event judged unlikely or unrelated to the study will also be included in an annual report for the IRB.

G. Statistical Considerations

1. Specific data variables being collected for the study.

   The data collection sheets will be submitted along with this protocol. There will be several data sheets as follows: 1) Spine surgeon's data sheet, 2) 30-day and 6-month morbidity data sheet, 3)1-year morbidity data sheet, 4) SF-36 questionnaires (pre-op, 3 months, 6 months, 1 year), 5) Oswestry Neck Disability Index questionnaires (pre-op, 3 months, 6 months, 1 year), 6)mJOA, (pre-op, 3 months, 6 months, 1 year), 7) Nurick questionnaire (pre-op, 3 months, 6 months, 1 year), 8)EuroQol-5D (pre-op, 3 months, 6 months, 1 year), 9)Radiology Review (pre-op, 3 months, 6 months, 1 year, 2 years).
2. Study endpoints.

   Patients will be followed for 1 year. The primary endpoints will be the SF-36 physical component summary score (PCS) and the Oswestry Neck Disability Index. Secondary endpoints will include the Nurick, mJOA, and EuroQol-5D scores as well as the observed complication rates. Radiographic fusion, instability, and deformity will also be secondary outcomes.
3. Statistical Methods.

   Analysis will focus on the physical component summary (PCS) of the SF-36, the Oswestry Neck Disability index, and the major complication rate. The t-test will be used to compare the groups for continuous variables such as the SF-36 PCS and the Oswestry Neck Disability Index. The Chi-square test will be used to compare the group's complication rates. Multiple regression techniques will be applied to control for potential confounders including age, medical condition, number of stenotic levels, degree of lordosis or kyphosis, etc.
4. Power Analysis.

The data generated from the SF-36 or the Oswestry Neck Disability Index will be used to calculate sample size for a future randomized controlled trial (RCT) comparing ventral to dorsal surgery. If no significant differences are identified in these primary outcomes measures, then a sample size calculation will be done using any differences in major complication rates.

Eligibility criteria: Inclusion Criteria:

* degenerative cervical spondylotic myelopathy (2 or more levels of spinal cord compression)

Exclusion Criteria:

* C2-C7 kyphosis\>5˚ (measured on lateral cervical spine image in extension)
* Segmental kyphotic deformity defined as 3 or more levels of disc-osteophyte extend dorsal to a line drawn from the dorsal caudal point of C2 to the dorsal caudal point of C7.
* Ossification of posterior longitudinal ligament (OPLL)
* Developmental narrow canal (\<12 mm-canal diameter measured on lateral plain cervical spine film)

Primary outcomes:
measure: Oswestry Neck Disability Index, mJOA, major complication rate
timeFrame: 1 year
Secondary outcomes:
measure: SF-36 physical component summary (PCS), EuroQol-5D
timeFrame: 1 year
Other outcomes:
Locations:
city: Danbury
country: United States
facility: Danbury Hospital
state: Connecticut
city: Greenwich
country: United States
facility: Greenwich Hospital
state: Connecticut
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Newark
country: United States
facility: University of Medicine and Dentistry - New Jersey
state: New Jersey
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Salt Lake City
country: United States
facility: University of Utah HSC
state: Utah
Study officials:
affiliation: Greenwich Hospital - Yale Universtiy School of Medicine
name: Zoher Ghogawala, MD, FACS
role: STUDY_DIRECTOR
affiliation: The Cleveland Clinic
name: Edward C. Benzel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Medicine and Dentistry of New Jersey
name: Robert Heary, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah
name: Ronald Apfelbaum
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Jean-Valery Coumans, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lahey Clinic
name: Subu N Magge, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fessler RG, Steck JC, Giovanini MA. Anterior cervical corpectomy for cervical spondylotic myelopathy. Neurosurgery. 1998 Aug;43(2):257-65; discussion 265-7. doi: 10.1097/00006123-199808000-00044.
citation: Edwards CC 2nd, Heller JG, Murakami H. Corpectomy versus laminoplasty for multilevel cervical myelopathy: an independent matched-cohort analysis. Spine (Phila Pa 1976). 2002 Jun 1;27(11):1168-75. doi: 10.1097/00007632-200206010-00007.
citation: Ghogawala Z, Coumans JV, Benzel EC, Stabile LM, Barker FG 2nd. Ventral versus dorsal decompression for cervical spondylotic myelopathy: surgeons' assessment of eligibility for randomization in a proposed randomized controlled trial: results of a survey of the Cervical Spine Research Society. Spine (Phila Pa 1976). 2007 Feb 15;32(4):429-36. doi: 10.1097/01.brs.0000255068.94058.8a.