Decompression alone versus decompression with instrumental fusion the NORDSTEN degenerative spondylolisthesis trial (NORDSTEN-DS); study protocol for a randomized controlled trial

Ivar Magne Austevoll, Erland Hermansen, Morten Fagerland, Frode Rekeland, Tore Solberg, Kjersti Storheim, Jens Ivar Brox, Greger Lønne, Kari Indrekvam, Jørn Aaen, Oliver Grundnes, Christian Hellum, Ivar Magne Austevoll, Erland Hermansen, Morten Fagerland, Frode Rekeland, Tore Solberg, Kjersti Storheim, Jens Ivar Brox, Greger Lønne, Kari Indrekvam, Jørn Aaen, Oliver Grundnes, Christian Hellum

Abstract

Background: Fusion in addition to decompression has become the standard treatment for lumbar spinal stenosis with degenerative spondylolisthesis (DS). The evidence for performing fusion among these patients is conflicting and there is a need for further investigation through studies of high quality. The present protocol describes an ongoing study with the primary aim of comparing the outcome between decompression alone and decompression with instrumented fusion. The secondary aim is to investigate whether predictors can be used to choose the best treatment for an individual. The trial, named the NORDSTEN-DS trial, is one of three studies in the Norwegian Degenerative Spinal Stenosis (NORDSTEN) study.

Methods: The NORDSTEN-DS trial is a block-randomized, controlled, multicenter, non-inferiority study with two parallel groups. The surgeons at the 15 participating hospitals decide whether a patient is eligible or not according to the inclusion and exclusion criteria. Participating patients are randomized to either a midline preserving decompression or a decompression followed by an instrumental fusion. Primary endpoint is the percentage of patients with an improvement in Oswestry Disability Index version 2.0 of more than 30% from baseline to 2-year follow-up. Secondary outcome measurements are the Zürich Claudication Questionnaire, Numeric Rating Scale for back and leg pain, Euroqol 5 dimensions questionnaire, Global perceived effect scale, complications and several radiological parameters. Analysis and interpretation of results will also be conducted after 5 and 10 years.

Conclusion: The NORDSTEN/DS trial has the potential to provide Level 1 evidence of whether decompression alone should be advocated as the preferred method or not. Further on the study will investigate whether predictors exist and if they can be used to make the appropriate choice for surgical treatment for this patient group.

Trial registration: ClinicalTrials.gov Identifier: NCT02051374 . First Posted: January 31, 2014. Last Update Posted: February 14, 2018.

Keywords: Clinical outcomes; Decompression; Degenerative spondylolisthesis; Fusion; NORDSTEN; Randomized controlled trial; Spinal stenosis.

Conflict of interest statement

Ethics approval and consent to participate

The patients are given verbal and written information about the study. If willing to participate, the patients sign an informed consent form. If a patient does not want to participate, he/she will receive normal care and be treated following the hospital’s established procedures.

The protocol has been approved by the Norwegian Committee for Medical and Health Research Ethics Midt (2013/366).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow-chart for NORDSTEN-DS. Legend: Eligibility, randomization, treatment and follow-up
Fig. 2
Fig. 2
Test for non-inferiority. Legend: The figure shows two alternative results for the primary outcome. DA and DF indicate the proportion of responders in the decompression alone group and decompression plus instrumented fusion group, respectively. The bars indicate the absolute difference in proportion of responders (DF-DA) with 95% confidence interval (CI) limits. Non-inferiority for DA is shown if the upper limit of the 95% CI for the difference is less than 15%

References

    1. Farfan HF (2012) - The pathological anatomy of degenerative spondylolisthesis. A cadaver study. - spine (Phila pa 1976)1980;5(5):412-8:Oct.
    1. Fitzgerald JA, Newman PH. Degenerative spondylolisthesis. J Bone Joint Surg Br. 1976;58:184–192. doi: 10.1302/0301-620X.58B2.932080.
    1. Watters WC, 3rd, Bono CM, Gilbert TJ, Kreiner DS, Mazanec DJ, Shaffer WO, Baisden J, Easa JE, Fernand R, Ghiselli G, Heggeness MH, Mendel RC, O'Neill C, Reitman CA, Resnick DK, Summers JT, Timmons RB, Toton JF, North American Spine S An evidence-based clinical guideline for the diagnosis and treatment of degenerative lumbar spondylolisthesis. Spine J. 2009;9:609–614. doi: 10.1016/j.spinee.2009.03.016.
    1. Herkowitz HN, Kurz LT. Degenerative lumbar spondylolisthesis with spinal stenosis. A prospective study comparing decompression with decompression and intertransverse process arthrodesis. J Bone Joint Surg Am. 1991;73:802–808. doi: 10.2106/00004623-199173060-00002.
    1. Martin CR, Gruszczynski AT, Braunsfurth HA, Fallatah SM, O'Neil J, Wai EK. The surgical management of degenerative lumbar spondylolisthesis: a systematic review. Spine. 2007;32:1791–1798. doi: 10.1097/BRS.0b013e3180bc219e.
    1. Resnick DK, Watters WC, 3rd, Sharan A, Mummaneni PV, Dailey AT, Wang JC, Choudhri TF, Eck J, Ghogawala Z, Groff MW, Dhall SS, Kaiser MG. Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 9: lumbar fusion for stenosis with spondylolisthesis. J Neurosurg Spine. 2014;21:54–61. doi: 10.3171/2014.4.spine14274.
    1. Steiger F, Becker HJ, Standaert CJ, Balague F, Vader JP, Porchet F, Mannion AF. Surgery in lumbar degenerative spondylolisthesis: indications, outcomes and complications. A systematic review. Eur Spine J. 2014;23:945–973. doi: 10.1007/s00586-013-3144-3.
    1. Ghogawala Z, Dziura J, Butler WE, Dai F, Terrin N, Magge SN, Coumans JV, Harrington JF, Amin-Hanjani S, Schwartz JS, Sonntag VK, Barker FG, 2nd, Benzel EC. Laminectomy plus fusion versus laminectomy alone for lumbar spondylolisthesis. N Engl J Med. 2016;374:1424–1434. doi: 10.1056/NEJMoa1508788.
    1. Chang HS, Fujisawa N, Tsuchiya T, Oya S, Matsui T. Degenerative spondylolisthesis does not affect the outcome of unilateral laminotomy with bilateral decompression in patients with lumbar stenosis. Spine. 2014;39:400–408. doi: 10.1097/BRS.0000000000000161.
    1. Forsth P, Michaelsson K, Sanden B (2013) Does fusion improve the outcome after decompressive surgery for lumbar spinal stenosis?: a two-year follow-up study involving 5390 patients. Bone joint J 95-B:960-965. 95-B/7/960;10.1302/0301-620X.95B7.30776.
    1. Austevoll IM, Gjestad R, Brox JI, Solberg TK, Storheim K, Rekeland F, Hermansen E, Indrekvam K, Hellum C. The effectiveness of decompression alone compared with additional fusion for lumbar spinal stenosis with degenerative spondylolisthesis: a pragmatic comparative non-inferiority observational study from the Norwegian registry for spine surgery. Eur Spine J. 2016. 10.1007/s00586-016-4683-1.
    1. Forsth P, Olafsson G, Carlsson T, Frost A, Borgstrom F, Fritzell P, Ohagen P, Michaelsson K, Sanden B. A randomized, controlled trial of fusion surgery for lumbar spinal stenosis. N Engl J Med. 2016;374:1413–1423. doi: 10.1056/NEJMoa1513721.
    1. Weinstein J, Pearson A. Fusion in degenerative spondylolisthesis becomes controversial … again. Evid Based Med. 2016;21:148–149. doi: 10.1136/ebmed-2016-110474.
    1. Peul WC, Moojen WA. Fusion for lumbar spinal stenosis--safeguard or superfluous surgical implant? N Engl J Med. 2016;374:1478–1479. doi: 10.1056/NEJMe1600955.
    1. Pearson AM. Fusion in degenerative spondylolisthesis: how to reconcile conflicting evidence. Journ Spine Surg. 2016;2:143–145. doi: 10.21037/jss.2016.06.02.
    1. Joaquim AF, Milano JB, Ghizoni E, Patel AA. Is there a role for decompression alone for treating symptomatic degenerative lumbar spondylolisthesis?: a systematic review. Clin Spine Surg. 2016;29:191–202. doi: 10.1097/bsd.0000000000000357.
    1. Angevine PD, Berven S. Health economic studies: an introduction to cost-benefit, cost-effectiveness, and cost-utility analyses. Spine. 2014;39:S9–15. doi: 10.1097/brs.0000000000000576.
    1. Hermansen E, Austevoll IM, Romild UK, Rekeland F, Solberg T, Storheim K, Grundnes O, Aaen J, Brox JI, Hellum C, Indrekvam K. Study-protocol for a randomized controlled trial comparing clinical and radiological results after three different posterior decompression techniques for lumbar spinal stenosis: the spinal stenosis trial (SST) (part of the NORDSTEN study) BMC Musculoskelet Disord. 2017;18:121. doi: 10.1186/s12891-017-1491-7.
    1. Agha RA, Altman DG, Rosin D. The SPIRIT 2013 statement--defining standard protocol items for trials. Int J Surg. 2015;13:288–291. doi: 10.1016/j.ijsu.2014.12.007.
    1. Piaggio GF, − Elbourne DR FAU - Altman D, − Altman DG FAU - Pocock S, − Pocock SJ FAU - Evans S, Evans SJ (2010) - Reporting of noninferiority and equivalence randomized trials: an extension of the CONSORT statement. - Jama 2006;295(10):1152–60:60.
    1. Fairbank JC, Couper J, Davies JB, O'Brien JP. The Oswestry low back pain disability questionnaire. Physiotherapy. 1980;66:271–273.
    1. Baker DJ, Pynsent PB, J F (1989) The Oswestry disability index revisited: its reliability, repeatability and validity, and a comparison with the St Thomas’s disability index. Roland MO, Jenner JR, eds New approaches to rehabilitation and education Manchester: Manchester University Press:174–186.
    1. Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, Haythornthwaite JA, Jensen MP, Kerns RD, Ader DN, Brandenburg N, Burke LB, Cella D, Chandler J, Cowan P, Dimitrova R, Dionne R, Hertz S, Jadad AR, Katz NP, Kehlet H, Kramer LD, Manning DC, McCormick C, McDermott MP, McQuay HJ, Patel S, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Revicki DA, Rothman M, Schmader KE, Stacey BR, Stauffer JW, von Stein T, White RE, Witter J, Zavisic S. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008;9:105–121. doi: 10.1016/j.jpain.2007.09.005.
    1. Ostelo RW, Deyo RA, Stratford P, Waddell G, Croft P, Von Korff M, Bouter LM, de Vet HC. Interpreting change scores for pain and functional status in low back pain: towards international consensus regarding minimal important change. Spine. 2008;33:90–94. doi: 10.1097/BRS.0b013e31815e3a10.
    1. Tuli SK, Yerby SA, Katz JN. Methodological approaches to developing criteria for improvement in lumbar spinal stenosis surgery. Spine. 2006;31:1276–80. 10.1097/01.brs.0000217615.20018.6c.
    1. (1990) EuroQol--a new facility for the measurement of health-related quality of life. Health policy (Amsterdam, Netherlands) 16:199–208.
    1. Kamper SJ, Ostelo RW, Knol DL, Maher CG, de Vet HC, Hancock MJ (2010) Global perceived effect scales provided reliable assessments of health transition in people with musculoskeletal disorders, but ratings are strongly influenced by current status. J Clin Epidemiol 63:760-766. Doi: S0895-4356(09)00304-7.
    1. Derogatis LR FAU, Lipman RS FAU, Rickels KF, Uhlenhuth EH FAU, Covi L, Derogatis LR FAU, Lipman RS FAU, Rickels KF, Uhlenhuth EH FAU, Covi L (2000) - The Hopkins symptom checklist (HSCL). A measure of primary symptom dimensions - the Hopkins symptom checklist (HSCL): a self-report symptom inventory Mod Probl Pharmacopsychiatry 1974;7(0):79–110:110.
    1. Schizas C, Theumann N, Burn A, Tansey R, Wardlaw D, Smith FW, Kulik G. Qualitative grading of severity of lumbar spinal stenosis based on the morphology of the dural sac on magnetic resonance images. Spine. 2010;35:1919–1924. doi: 10.1097/BRS.0b013e3181d359bd.
    1. Lee S, Lee JW, Yeom JS, Kim KJ, Kim HJ, Chung SK, Kang HS (2010) A practical MRI grading system for lumbar foraminal stenosis. AJR Am J Roentgenol 194:1095-1098. doi: 194/4/1095;10.2214/AJR.09.2772 [doi].
    1. Dupuis PR, Yong-Hing K, Cassidy JD, Kirkaldy-Willis WH Radiologic diagnosis of degenerative lumbar spinal instability. Spine. 1985; 10:262–276.
    1. Berlemann UF, Jeszenszky DJ FAU, Buhler DW FAU, Harms J (2005) - Facet joint remodeling in degenerative spondylolisthesis: an investigation of joint orientation and tropism. - Eur Spine J 1998;7(5):376-80:80.
    1. Cho IY, Park SY, Park JH, Suh SW, Lee SH. MRI findings of lumbar spine instability in degenerative spondylolisthesis. J Orthop Surg (Hong Kong). 2017;25:2309499017718907. 10.1177/2309499017718907.
    1. Pfirrmann CW, Metzdorf A, Zanetti M, Hodler J, Boos N. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine (Phila Pa 1976) 2001;26:1873–1878. doi: 10.1097/00007632-200109010-00011.
    1. Modic MT, Steinberg PM, Ross JS, Masaryk TJ, Carter JR Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology. 1988 166:193–199. 10.1148/radiology.166.1.3336678.
    1. Masharawi Y, Kjaer P, Bendix T, Manniche C, Wedderkopp N, Sorensen JS, Peled N, Jensen TS. The reproducibility of quantitative measurements in lumbar magnetic resonance imaging of children from the general population. Spine. 2008;33:2094–2100. doi: 10.1097/BRS.0b013e31817f19f7.
    1. Schwab F, Lafage V, Patel A, Farcy JP. Sagittal plane considerations and the pelvis in the adult patient. Spine. 2009;34:1828–1833. doi: 10.1097/BRS.0b013e3181a13c08.
    1. Bridwell KH, Lenke LG, McEnery KW, Baldus C, Blanke K. Anterior fresh frozen structural allografts in the thoracic and lumbar spine. Do they work if combined with posterior fusion and instrumentation in adult patients with kyphosis or anterior column defects? Spine. 1995;20:1410–1418. doi: 10.1097/00007632-199506020-00014.
    1. Blackwelder WC, Chang MA. Sample size graphs for "proving the null hypothesis". Control Clin Trials. 1984;5:97–105. doi: 10.1016/0197-2456(84)90116-8.
    1. Katz NP, Paillard FC, Ekman E. Determining the clinical importance of treatment benefits for interventions for painful orthopedic conditions. J Orthop Surgery Res. 2015;10:24. doi: 10.1186/s13018-014-0144-x.
    1. Blumenthal S, McAfee PC, Guyer RD, Hochschuler SH, Geisler FH, Holt RT, Garcia R, Jr, Regan JJ, Ohnmeiss DD. A prospective, randomized, multicenter Food and Drug Administration investigational device exemptions study of lumbar total disc replacement with the CHARITE artificial disc versus lumbar fusion: part I: evaluation of clinical outcomes. Spine. 2005;30:1565–1575. doi: 10.1097/01.brs.0000170587.32676.0e.
    1. Katz N, Paillard FC, Van Inwegen R. A review of the use of the number needed to treat to evaluate the efficacy of analgesics. J Pain. 2015;16:116–123. doi: 10.1016/j.jpain.2014.08.005.
    1. Fagerland MW, Lydersen S, Laake P (2011) Recommended confidence intervals for two independent binomial proportions. Stat Methods Med Res. Doi: 0962280211415469 ;10.1177/0962280211415469 [doi].
    1. Hosmer DW, Lemeshow S. Applied logistic regression. 2. New York: John Wiley & Sons, Inc, Hoboken; 2000.
    1. Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source Code Biol Med. 2008;3:17. doi: 10.1186/1751-0473-3-17.
    1. Conroy RM, Pyorala K, Fitzgerald AP, Sans S, Menotti A, De Backer G, De Bacquer D, Ducimetiere P, Jousilahti P, Keil U, Njolstad I, Oganov RG, Thomsen T, Tunstall-Pedoe H, Tverdal A, Wedel H, Whincup P, Wilhelmsen L, Graham IM. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24:987–1003. doi: 10.1016/S0195-668X(03)00114-3.
    1. Solberg IC, Hoivik ML, Cvancarova M, Moum B. Risk matrix model for prediction of colectomy in a population-based study of ulcerative colitis patients (the IBSEN study) Scand J Gastroenterol. 2015;50:1456–1462. doi: 10.3109/00365521.2015.1064991.
    1. Drummond M (2005) Methods for the economic evaluation of health care Programmes. 3rd ed Oxford, NY : Oxford medical publications, Oxford University press;
    1. Lonne G, Johnsen LG, Aas E, Lydersen S, Andresen H, Ronning R, Nygaard OP. Comparing cost-effectiveness of X-stop with minimally invasive decompression in lumbar spinal stenosis: a randomized controlled trial. Spine. 2015;40:514–520. doi: 10.1097/brs.0000000000000798.
    1. ICH, Harmonised, Tripartite, Guideline (2014) Guideline for good clinical practice E6(R1). 1996. .

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe