Clinical trial NCT04623593: Cervical Arthroplasty Cost Effectiveness Study (CACES)
Official title: Economic Evaluation of Anterior Cervical Discectomy With Arthroplasty Versus Anterior Cervical Discectomy With Fusion in the Surgical Treatment of Cervical Degenerative Disc Disease, a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Radiculopathy, Cervical
Myelopathy Cervical
Myelopathy, Compressive
Radiculopathy, Cervical Region
Radiculopathy; in Spondylosis
Radiculopathy; in Intervertebral Disc Disorder
Myelopathy Neurological
Myelopathy Due to Spondylosis
Cervical Disc Disease
Cervical Disc Herniation
Cervical Disc Degeneration
Cervical Disc Disorder With Myelopathy
Cervical Disc Prolapse With Myelopathy
Cervical Spondylosis
Cervical Fusion
Cervical Disc Disorder With Radiculopathy
Cervical Disc Prolapse With Radiculopathy
Fusion of Spine
Disc Prolapse Cervical
Keywords: Cost-effectivity
Economic evaluation
Health Utility
Randomised controlled trial
RCT
ACDA
ACDF
Anterior cervical discectomy and fusion
Anterior cervical discectomy with arthroplasty
Degenerative cervical myelopathy
Degenerative cervical radiculopathy
ASD
Adjacent Segment Disease
Adjacent Level Disease
Lead sponsor: Zuyderland Medisch Centrum
Sponsor class: OTHER
First posted: 2020-11-10
Enrollment: 198
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective Single-blind Randomised Controlled Trial with computer randomization in a 1:1 ratio
Primary purpose: TREATMENT

Brief summary: To date, no consensus exists on which anterior surgical technique is more cost-effective to treat cervical degenerative disc disease (CDDD). The most commonly used surgical treatment for patients with single- or multilevel symptomatic CDDD is anterior cervical discectomy with fusion (ACDF). However, new complaints of radiculopathy and/or myelopathy commonly develop at adjacent levels, also known as clinical adjacent segment pathology (CASP). It remains unknown to what extent kinematics, surgery-induced fusion and natural history of disease play a role in its development. Anterior cervical discectomy with arthroplasty (ACDA) is thought to reduce the incidence of CASP by preserving motion in the operated segment. ACDA is often discouraged as the implant costs are higher whilst the clinical outcomes are similar to ACDF. However, preventing CASP might be a reason for ACDA to be a more cost-effective technique in the long-term.

In this randomized controlled trial patients will be randomized to receive ACDF or ACDA in a 1:1 ratio. Adult patients with single- or multi-level CDDD and symptoms of radiculopathy and/or myelopathy will be included. The primary outcome is cost-effectiveness and cost-utility of both techniques from a societal perspective. Secondary objectives are the differences in clinical and radiological outcomes between the two techniques, as well as the qualitative process surrounding anterior decompression surgery. All outcomes will be measured at baseline and every 6 months till 4 years postoperatively.

High quality evidence regarding the cost-effectiveness of both ACDA and ACDF is lacking, to date no prospective trials from a societal perspective exist. Considering the ageing of the population and the rising healthcare costs, the need for a solid clinical cost-effectiveness trial addressing this question is high.

Detailed description: Cervical degenerative disc disease (CDDD) is the degeneration of a cervical intervertebral disc and/or the adjoining vertebral bodies, resulting in clinical symptoms of cervical radiculopathy, myelopathy, myeloradiculopathy, and axial pain. The incidence of degenerative pathologies is significantly increasing as the population of elderly is rising. Currently, generalized spinal disc degeneration occurs in more than 90% of adults past the 5th decade of life.This age group now represents 32.8% of the population in Europe and is projected to reach 40.6% by 2050. In the next 20 years a significant increase in anterior cervical decompression surgeries is predicted in those aged 45-54, mainly affecting the working population. Complaints of radiculopathy and/or myelopathy lead to restrictions in daily life and loss of professional capability, resulting in absenteeism. Societal healthcare costs are therefore significantly affected by CDDD. The healthcare costs are driven up further when patients require surgical treatment, in combination with associated hospitalization and rehabilitation. To date, no consensus exists on which anterior surgical technique is more cost-effective to treat CDDD with radiculopathy and/or myelopathy.

One of the most common procedures for treating patients with single- or multilevel CDDD is anterior cervical discectomy with fusion (ACDF). ACDF results in fusion in 95-100%. The primary goal of ACD(F) is the relief of symptoms of radiculopathy and/or myelopathy through decompression of neural structures. Fusion in itself is not a requisite to reach this goal. In our center, ACDF with stand-alone cages is the standard procedure for CDDD. Plate-constructs are only used on indication. A common concern regarding ACDF with stand-alone cages is the occurrence of cage subsidence. In our retrospective cohort of 673 patients, only 1 patient required additional surgery due to subsidence (0.15%) \[unpublished data\]. Axial pain alone is not considered an indication for surgical treatment. Good short-term clinical results are achieved for both radiculopathy and myelopathy. Clinical results are independent from the technique used, and independent from occurrence of fusion. However, patient-reported satisfaction gradually decreases in the years following surgery. This is thought to be the consequence of the development of new complaints due to degenerative changes at a segment adjacent to the site of the index surgery, also known as adjacent segment pathology (ASP).

A recent consensus proposes a distinct definition of radiologic adjacent segment pathology (RASP) and clinical adjacent segment pathology (CASP). CASP occurs at an estimated cumulative rate of 1.6% to 4.2% per year after ACDF, however, a wide variety in incidence is reported in literature. About 50-75% of the patients that develop CASP require additional adjacent segment surgery. In our retrospective cohort, we observed a rate of 2.1% CASP per year, with an additional adjacent segment surgery rate of 1.5% per year. Moreover, we found that half of these patients undergo additional surgery for CASP within 2.5 years, which suggests a peak incidence in the first years following index surgery. The underlying mechanism of ASP remains a matter of debate. Besides natural degeneration, compensation for the loss of motion in the fused segment is thought to cause overstraining of the adjacent segments. Altered cervical sagittal alignment is also thought to be of importance in the accelerated development of CASP. Higher rates of CASP are observed after ACD, concomitant with an increased segmental kyphosis at the index level. Unlike ACD, ACDF with plate-constructs restore cervical sagittal lordosis. However, a higher rate of ASP is observed in those with plate-constructs in comparison to ACDF with stand-alone cages. The higher rate of ASP after ACDF with plate-constructs might be explained by strain on the adjacent segments by the plate, or more extensive surgical preparation for installing the plate increasing the chance on destruction of the adjacent level. Another contributing factor might be the occurrence of subsidence of the plate-construct into the adjacent segment. Disc height at the adjacent segments is found to be significantly decreased in those with plate-constructs, which supports this theory. It remains unknown to what extent altered cervical motion influences the development of ASP.

Anterior cervical discectomy with arthroplasty (ACDA) was developed to reduce the incidence of CASP by preserving motion in the operated segment. Previously conducted research in patients with radiculopathy and/or myelopathy has shown no significant differences in clinical or radiological outcomes amongst ACDA and ACD(F). A meta-analysis found better neurological outcomes in patients with myelopathy after ACDA, in contrast to the pre-existing notion that ACDA leads to less favorable outcomes in myelopathy due to micro-trauma caused by preserved mobility. Moreover, additional adjacent segment surgery rates are significantly lower for ACDA, both for single- and multilevel surgeries. The difference in additional adjacent segment surgery rates between ACDA and ACDF expands exponentially with a longer-follow-up time. ACDA is often discouraged as the implant costs are higher than those for ACDF whilst clinical outcomes are similar. However, preventing new complaints and additional surgeries due to CASP might be a reason for ACDA to be a more cost-effective technique in the long-term. A systematic review of economic evaluations in anterior cervical decompression surgery was conducted by our research group. The majority of studies report ACDA to be the most cost-effective technique despite higher implant costs. Literature was however strongly heterogeneous and of low quality.

In conclusion, there is increasing evidence suggesting that ACDA might be the more cost-effective technique because of a reduced risk on CASP and associated additional surgery rates, compared to ACD(F). High quality evidence regarding the cost-effectiveness of both ACDA and ACDF is lacking, especially in Europe. Therefore, the need for a solid clinical cost-effectiveness trial addressing this question is high.

Eligibility criteria: Inclusion Criteria:

* Indication for anterior cervical decompression surgery.
* Single- or multilevel CDDD between C3 and C7.
* Symptoms of myelopathy, radiculopathy, or myeloradiculopathy.
* In case of pure radiculopathy: refractory to at least 6 weeks of conservative therapy.
* In case of myelopathy: symptomatic myelopathy.
* Patients ≥ 18 years of age.

Exclusion criteria

* Indication for (additional) posterior surgical approach.
* Indication for additional stabilization of the pathological segment by a plate.
* Previous ventral surgery of the cervical spine.
* Traumatic origin of the compression.
* Previous radiotherapy of the cervical spine.
* Metabolic bone disease.
* Inflammatory spinal disease: e.g., Bechterew's disease, Forestier's disease.
* Infection of the cervical spine.

Primary outcomes:
measure: Costs
timeFrame: 4 years
measure: Effectiveness
timeFrame: 4 years
Secondary outcomes:
measure: CASP
timeFrame: 4 years
measure: Radiological Outcomes
timeFrame: 1 year
measure: Neck Disability Index (NDI).
timeFrame: 4 years
measure: Visual Analogue Scale (VAS) for neck and arm pain.
timeFrame: 4 years
measure: Hospital Anxiety Depression Scale (HADS)
timeFrame: 4 years
measure: modified Japanese Orthopedic Association score (mJOA)
timeFrame: 4 years
measure: Process Evaluation
timeFrame: 4 years
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: Zuyderland Medical Center
state: Limburg
Study officials:
affiliation: Maastricht University Medical Center
name: Anouk Smeets, MD, PhD, Professor
role: PRINCIPAL_INVESTIGATOR
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