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Radiculopathy, CervicalCACESNCT04623593

Cervical Arthroplasty Cost Effectiveness Study (CACES)

A study testing ACDF and ACDA in people with Radiculopathy, Cervical and Myelopathy Cervical, run by Valérie Schuermans at 1 site in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ACDF and ACDA
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
198 participants
Where
1 siteNetherlands
Study dates
17 Jan 2022to 1 Jun 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Valérie Schuermans, MD contact

0031433875001

valerie.schuermans@mumc.nl

Anouk Smeets, MD, PhD contact

0031433875001

anouk.smeets@mumc.nl

Netherlands1 site, 1 recruiting

  • Zuyderland Medical Center

    Maastricht, Limburg, 6419 PC

    Valerie Schuermans, MD, v.schuermans@zuyderland.nl

    Recruiting

Other trials in Netherlands

About this study

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

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.

Read the 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.

Being tested
ACDF, ACDA
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
Medical subject headings
Radiculopathy, Spinal Cord Compression, Spinal Cord Diseases, Spondylosis, Klippel-Feil Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ACDFProcedure or surgery

    Also called Anterior Cervical Discectomy and Fusion

    Standard operative treatment for anterior cervical discectomy. Through a right or left-sided approach the disc space contents are resected. The endplates are prepared with curettes and the disc space contents are removed. The posterior longitudinal ligament is opened. The dura is visualized to ensure adequate decompression. A cage is implanted in the disc space. The disc removal and cage implantation can be performed at a single level or at multiple levels. The wound is closed in layers, after a prevertebral wound drain is placed.

  • ACDAProcedure or surgery

    Also called Anterior Cervical Discectomy and arthroplasty

    The start of the procedure is the same as in the ACDF group. After the discectomy, a cervical disc prosthesis is placed in the disc space instead of a cage, in accordance with the manufacturer's protocol for implantation and endplate preparation. The disc removal and arthrodesis implantation can be performed at a single level or at multiple levels. Wound closure is similar to the ACDF procedure.

Study groups in NCT04623593
Study groupRoleWhat they receive
ACDFActive comparatorAnterior cervical discectomy and fusion.
Receives: Procedure: ACDF
ACDAExperimentalAnterior cervical discectomy with arthroplasty.
Receives: Procedure: ACDA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Costs

    Costs will be determined from a societal perspective.

    Validated cost questionnaires for societal costs, including medical consumption, both paid and unpaid loss of productivity for patients. :

    • Productivity Cost Questionnaire (iPCQ) for measuring productivity loss for work loss (paid and unpaid). Consists of 7 questions.
    • the Medical Consumption Questionnaire (iMCQ) for measuring medical consumption, especially designed for the Dutch health care environment. Consists of 14 questions.

    Informal caregivers will be asked to fill out the Limited Valuation of Informal Care Questionnaire (iVICQ):

    • informal care giver (ICG) productivity loss for work loss (paid and unpaid)
    • Care-related Quality of Life instrument (CarerQol-7D).
    • The Self-Rated Burden scale (SRB), a horizontal 'visual-analog scale' to determine the subjective burden of the caregiver on a scale from 0 (not heavy) to 10 (very heavy).

    Measured: 4 years

  2. Effectiveness

    In the CUA, the Incremental Cost-Effectiveness Ratio (ICER) will be expressed as the incremental costs per QALY.

    Quality Adjusted Life Years (QALYs) will be determined by Generic Quality of Life assessed based on the EuroQol utility scores (EQ-5D-5L). The EQ-5D-5L essentially consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).

    The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.

    Measured: 4 years

Secondary outcomes (7)

  1. CASP

    The rate of clinical adjacent segment pathology and associated additional surgeries will be assessed.

    Measured: 4 years

  2. Radiological Outcomes

    At 3 time points; pre-operatively, directly post-operative and one-year post-operative.

    • Pre-operative imaging will assess baseline degeneration according to the Kellgren-Lawrence Score, cervical sagittal alignment and baseline disc height. Moreover, a full sagittal spine X-ray will be made to assess pre-operative global balance according to the odontoid-hip axis.
    • Post-operative: A standard cervical spine X-ray to assess the position of the implant, subsidence and cervical sagittal alignment.
    • 1 year post-operative cervical spine X-rays will be made. A standard cervical spine X-ray will be made to assess fusion, cage subsidence, adjacent segment degeneration (KS), adjacent segment disc height and alignment. A flexion and extension X-ray will be made to assess movement.

    Measured: 1 year

  3. Neck Disability Index (NDI).

    It is a patient-completed, condition-specific functional status questionnaire with 10 items including pain, personal care, lifting, reading, headaches, concentration, work, driving, sleeping, and recreation. Each question is scored on a 0-5 scale, where 0 is no disability and 5 is the maximal disability possible

    Measured: 4 years

  4. Visual Analogue Scale (VAS) for neck and arm pain.

    Visual Analogue Scale (VAS) for neck and arm pain. Neck and arm pain are assessed separately on a horizontal 10 cm visual scale, varying from 0 cm (no pain) to 10 cm (worst pain imaginable)

    Measured: 4 years

  5. Hospital Anxiety Depression Scale (HADS)

    A fourteen-item scale, to determine the anxiety and depression level. Consisting of a 7-item depression scale and a 7-item anxiety scale. The score ranges from 0-21 with a high score being indicative for depression/anxiety (≥ 8)

    Measured: 4 years

  6. modified Japanese Orthopedic Association score (mJOA)

    modified Japanese Orthopedic Association score (mJOA) for myelopathy. patients. An investigator-administered tool used to evaluate neurological function in patients with cervical myelopathy. It is an 18-point scale that addresses upper (5 points) and lower extremity (7 points) motor function, sensation (3 points) and micturition (3 points). A score of 18 reflects no neurological deficits whereas a lower score indicates a greater degree of disability and functional impairment

    Measured: 4 years

  7. Process Evaluation

    Moreover, a process evaluation will be performed to determine the underlying values, needs, impacts and preferences of people with CDDD. The focus will be experiences and opinions of patients, caregivers, and professionals concerning the process surrounding ACDA and ACDF. A process evaluation might also identify gaps or limitations in published research with regards to important outcomes to those with lived experience. A qualitative analysis will be performed according to the framework provided by Saunders et al.

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Nov 2020
  2. Study start17 Jan 2022
  3. Primary completion1 Jun 2026 (estimated)
  4. Study completion1 Jun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Prospective Single-blind Randomised Controlled Trial with computer randomization in a 1:1 ratio
Masking
Single blind
Who is masked
Participant
Enrolment
198 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04623593
Sponsor's protocol ID
NL72534.096.20
Acronym
CACES
Status last verified
Jan 2024
First submitted
29 Sep 2020
Last updated
25 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Radhakrishnan K, Litchy WJ, O'Fallon WM, Kurland LT. Epidemiology of cervical radiculopathy. A population-based study from Rochester, Minnesota, 1976 through 1990. Brain. 1994 Apr;117 ( Pt 2):325-35. doi: 10.1093/brain/117.2.325.

    PubMed 8186959

  • Salemi G, Savettieri G, Meneghini F, Di Benedetto ME, Ragonese P, Morgante L, Reggio A, Patti F, Grigoletto F, Di Perri R. Prevalence of cervical spondylotic radiculopathy: a door-to-door survey in a Sicilian municipality. Acta Neurol Scand. 1996 Feb-Mar;93(2-3):184-8. doi: 10.1111/j.1600-0404.1996.tb00196.x.

    PubMed 8741140

  • McCartney S, Baskerville R, Blagg S, McCartney D. Cervical radiculopathy and cervical myelopathy: diagnosis and management in primary care. Br J Gen Pract. 2018 Jan;68(666):44-46. doi: 10.3399/bjgp17X694361. No abstract available.

    PubMed 29284641

  • Boogaarts HD, Bartels RH. Prevalence of cervical spondylotic myelopathy. Eur Spine J. 2015 Apr;24 Suppl 2:139-41. doi: 10.1007/s00586-013-2781-x. Epub 2013 Apr 25.

    PubMed 23616201

  • Kuijper B, Tans JT, Schimsheimer RJ, van der Kallen BF, Beelen A, Nollet F, de Visser M. Degenerative cervical radiculopathy: diagnosis and conservative treatment. A review. Eur J Neurol. 2009 Jan;16(1):15-20. doi: 10.1111/j.1468-1331.2008.02365.x.

    PubMed 19087147

  • Saal JS, Saal JA, Yurth EF. Nonoperative management of herniated cervical intervertebral disc with radiculopathy. Spine (Phila Pa 1976). 1996 Aug 15;21(16):1877-83. doi: 10.1097/00007632-199608150-00008.

    PubMed 8875719

  • Fehlings MG, Tetreault LA, Riew KD, Middleton JW, Aarabi B, Arnold PM, Brodke DS, Burns AS, Carette S, Chen R, Chiba K, Dettori JR, Furlan JC, Harrop JS, Holly LT, Kalsi-Ryan S, Kotter M, Kwon BK, Martin AR, Milligan J, Nakashima H, Nagoshi N, Rhee J, Singh A, Skelly AC, Sodhi S, Wilson JR, Yee A, Wang JC. A Clinical Practice Guideline for the Management of Patients With Degenerative Cervical Myelopathy: Recommendations for Patients With Mild, Moderate, and Severe Disease and Nonmyelopathic Patients With Evidence of Cord Compression. Global Spine J. 2017 Sep;7(3 Suppl):70S-83S. doi: 10.1177/2192568217701914. Epub 2017 Sep 5.

    PubMed 29164035

  • Badhiwala JH, Wilson JR. The Natural History of Degenerative Cervical Myelopathy. Neurosurg Clin N Am. 2018 Jan;29(1):21-32. doi: 10.1016/j.nec.2017.09.002. Epub 2017 Oct 27.

    PubMed 29173433

  • Dowd GC, Wirth FP. Anterior cervical discectomy: is fusion necessary? J Neurosurg. 1999 Jan;90(1 Suppl):8-12. doi: 10.3171/spi.1999.90.1.0008.

    PubMed 10413119

  • Donk RD, Verbeek ALM, Verhagen WIM, Groenewoud H, Hosman AJF, Bartels RHMA. What's the best surgical treatment for patients with cervical radiculopathy due to single-level degenerative disease? A randomized controlled trial. PLoS One. 2017 Aug 29;12(8):e0183603. doi: 10.1371/journal.pone.0183603. eCollection 2017.

    PubMed 28850600

  • Nandoe Tewarie RD, Bartels RH, Peul WC. Long-term outcome after anterior cervical discectomy without fusion. Eur Spine J. 2007 Sep;16(9):1411-6. doi: 10.1007/s00586-007-0309-y. Epub 2007 Jan 30.

    PubMed 17262184

  • Hilibrand AS, Carlson GD, Palumbo MA, Jones PK, Bohlman HH. Radiculopathy and myelopathy at segments adjacent to the site of a previous anterior cervical arthrodesis. J Bone Joint Surg Am. 1999 Apr;81(4):519-28. doi: 10.2106/00004623-199904000-00009.

    PubMed 10225797

  • Eck JC, Humphreys SC, Lim TH, Jeong ST, Kim JG, Hodges SD, An HS. Biomechanical study on the effect of cervical spine fusion on adjacent-level intradiscal pressure and segmental motion. Spine (Phila Pa 1976). 2002 Nov 15;27(22):2431-4. doi: 10.1097/00007632-200211150-00003.

    PubMed 12435970

  • Boselie TF, Willems PC, van Mameren H, de Bie RA, Benzel EC, van Santbrink H. Arthroplasty versus fusion in single-level cervical degenerative disc disease: a Cochrane review. Spine (Phila Pa 1976). 2013 Aug 1;38(17):E1096-107. doi: 10.1097/BRS.0b013e3182994a32.

    PubMed 23656959

  • Boselie TF, van Santbrink H. Arthroplasty in cervical degenerative disc disease: fulfilling its long-term promise? J Spine Surg. 2016 Dec;2(4):359-361. doi: 10.21037/jss.2016.12.01. No abstract available.

    PubMed 28097260

Questions about this trial

What is this clinical trial studying?

A study testing ACDF and ACDA in people with Radiculopathy, Cervical and Myelopathy Cervical, run by Valérie Schuermans at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Valérie Schuermans, MD (0031433875001, valerie.schuermans@mumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Costs (time frame: 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04623593, which also lists 48 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2024.

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