Long-term Reoperations After Lumbar Spinal Stenosis Surgery

Degenerative Lumbar Spondylolisthesis Clinical Trial

Official title:

Long-term Frequency of Reoperations After Micro-decompression Alone Versus Decompression and Instrumented Fusion in Patients With Lumbar Spinal Stenosis and Degenereative Spondylolisthesis

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06407063
• Other study ID #: 2813
• Status: Active, not recruiting
• Start date: September 19, 2007
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: University Hospital of North Norway
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Severe and persisting pain and disability due to a degenerative narrowing of the spinal canal, lumbar spinal stenosis, can be operated with a simple surgical decompression. Sometimes, there is also a slippage of vertebra, degenerative spondylolisthesis. In such cases, instrumental stabilization (e.g. screws and rods) has been recommended. Even though additional fusion is more complex and riskier, and evidence in high-quality Scandinavian studies shows that it is unnecessary, decompression plus fusion is still the treatment of choice in the USA and most European countries. This reluctance to change clinical practice is mainly due to concerns about long-term results, especially higher reoperation rates among patients operated with decompression only. This register-based non-inferiority study aims to assess long-term reoperations among those treated with and without additional fusion surgery.

Description:

The use of fusion surgery in addition to decompression in the treatment of degenerative lumbar spondylolisthesis (DS) with spinal stenosis (LSS) is a long-standing controversy in spine surgery. The main goal of LSS surgery is to decompress the nerve roots. In the 1990s, two observational studies recommended that decompression with additional fusion should be the treatment of choice (1, 2). Consequently, the practice shifted towards more complex fusion procedures. In 2016, two randomized controlled trials (RCTs) reported conflicting data about reoperations. The American study showed a higher frequency of reoperations in the decompression arm compared to the decompression and fusion arm (3), while the Swedish study showed no difference (4). In 2020, Austevoll et. al. published an observational relative effectiveness study from the Norwegian registry for spine surgery (NORspine) comparing micro-decompression alone vs decompression and instrumented fusion (5). The study had a non-inferiority design, similar to the RCT published by the same author in 2021 (6). Both studies concluded that micro-decompression alone was non-inferior to decompression and instrumented fusion regarding clinical outcomes and reoperation rates. Despite an increasing number of studies showing no extra benefits from the more risky and complex additional fusion procedures, the surgical practice has changed little outside Scandinavia. This is probably due to the concerns about subsequent instability and higher long-term reoperation rates among those operated with decompression only.

This study is a long-term follow-up of the previously mentioned NORspine study (5)(NCT03469791), comprising 794 patients having an index operation for LSS and DS between September 19th 2007 and December 21st 2015. The present study aims to assess long-term reoperations resulting from everyday clinical practice. We hypothesise that micro-decompression alone is non-inferior to decompression plus instrumented fusion. The non-inferior margin is specified to correspond to a number needed to treat = 8 to avoid reoperation on one patient in the first 10 postoperative years, corresponding to a between-group difference of 12.5 percentage points (100/8 = 12.5).

Our dataset contains NORspine data at baseline, 3 months, one year and long-term follow-up performed at 7 to 15 years (NCT03469791). NORspine also provides dates of death for all deceased patients. The Norwegian Patient Registry (NPR) will serve as an external data source, providing data about all reoperations until August 31st 2023 and the baseline Charlson Comorbidity Index (CCI). NPR data will ensure follow-up of 8 to 16 years concerning reoperations. For these cases, we will review the electronic health records to validate NPR data regarding classification of reoperation (level, indication, surgical technique, total number of reoperations, spinal cord stimulation, reoperations within 90 days after the index operation, participation in other studies).

In the short-term follow-up study (5)(NCT03469791) propensity score matching (PSM) was performed to reduce the risk of allocation bias. We will reuse this matching. PSM is used to make the distribution of observed baseline patient characteristics in the micro-decompression and instrumented fusion group as similar as possible. The following parameters were included in the calculation of the propensity score: Age; Gender; American Society of Anaesthesiologists (ASA) grade; Body Mass Index (BMI); Smoking, Oswestry Disability Index (ODI), Numeric Rating Scale for leg pain and back pain, Euroqol 5D (EQ-5D-3L), foraminal stenosis, degenerative disc disease, predominating back pain, number of levels operated on and neurological palsy. The propensity scores were derived from a logistic regression model and reflected a patient's theoretical baseline probability for being instrumentally fused. Using the '1:1 matching without replacement' method, pairs of fused and non-fused patients with a difference in propensity scores less than 0.2 in the logit of the standard deviation were formed. Statistical Package for the Social Sciences (SPSS) version 24 was used for propensity score matching. For comparison, complete case analyses will also be performed.

In this non-inferiority designed study with one sided testing, our primary outcome is the occurrence of a reoperation, defined as new lumbar spine operation more than 90 days after the index operation, during the observation period, i.e. from 90 days after index operation until August 31st 2023 years (range from 8 to 16 years). We will use survival analysis to detect whether the probability for reoperation during the first 10 postoperative years is more than 12.5 % higher (non-inferiority margin) in the micro-decompression group than in the decompression and instrumented fusion group. This is to be tested by deriving a 90 % confidence interval (CI) for the difference of the survival function (S(t)) at 10 years between the groups (S(t) in decompression and instrumented fusion group - S(t) in micro-decompression group) where t = 10 years, and rejected if the lower limit of the CI is above -0.125. If this is rejected the conclusion will be that, in the setting of everyday clinical practice, micro-decompression is non-inferior to decompression and instrumented fusion regarding the risk of reoperation. We will further report the survival functions and observed reoperation rates at multiple timepoints (2, 5 and 10 years), hazard ratio (HR) for reoperation (at 2, 5 and 10 years if the proportional hazard assumption in violated), as well as complications (including reoperations within 90 days). We will also investigate the indication for reoperation, surgical techniques used and risk factors associated with reoperation.

For the power analysis conducted with PASS 2019, we made two assumptions. 1) Expected reoperation rate: Based on NORspine data, about 27.1 % of lumbar surgical procedures are performed on patients previously operated on in the lumbar spine. We use this as a proxy for the expected probability of the event (reoperation) in the total cohort. 2) HR = 1.6 (decompression and instrumented fusion as baseline) approximates the event ratio between the groups. This non-inferiority margin, choosing a type 1 error = 0.05 and power 0.8 gives sample size = 269 per group. Our sample size is 285 per group, and since our data source are national administrative registries and patient's health records, we do not expect substantial loss to follow-up.

We will employ SAS Enterprise Guide 8.3 for analyses, including descriptive statistics, tests for data distribution, cross-tabulations with χ2 test, Student t-tests, and Mann-Whitney U tests. Reoperation survival, hazard and rates will be assessed by stratified log-rank test, cox regression modelling (time-dependent if the proportional hazard assumption is violated), Kaplan-Meier plots and multivariable regression analyses.

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(6):802-8.

2. Bridwell KH, Sedgewick TA, O'Brien MF, Lenke LG, Baldus C. The role of fusion and instrumentation in the treatment of degenerative spondylolisthesis with spinal stenosis. J Spinal Disord. 1993;6(6):461-72.

3. Ghogawala Z, Dziura J, Butler WE, Dai F, Terrin N, Magge SN, et al. Laminectomy plus Fusion versus Laminectomy Alone for Lumbar Spondylolisthesis. N Engl J Med. 2016;374(15):1424-34.

4. Försth P, Ólafsson G, Carlsson T, Frost A, Borgström F, Fritzell P, et al. A Randomized, Controlled Trial of Fusion Surgery for Lumbar Spinal Stenosis. N Engl J Med. 2016;374(15):1413-23.

5. Austevoll IM, Gjestad R, Solberg T, Storheim K, Brox JI, Hermansen E, et al. Comparative Effectiveness of Microdecompression Alone vs Decompression Plus Instrumented Fusion in Lumbar Degenerative Spondylolisthesis. JAMA Netw Open. 2020;3(9):e2015015.

6. Austevoll IM, Hermansen E, Fagerland MW, Storheim K, Brox JI, Solberg T, et al. Decompression with or without Fusion in Degenerative Lumbar Spondylolisthesis. N Engl J Med. 2021;385(6):526-38.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 794
• Est. completion date: December 31, 2024
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• operated between September 2007 and December 2015 labeled in the registry with both 'Spinal stenosis' and 'Degenerative spondylolisthesis'

• operated on with decompression with or without an additional fusion

Exclusion Criteria:

• operated with an anterior approach

• had a former operation at index Level

• was labeled with a degenerative scoliose

• was operated in more than 2 Levels

• was operated with non-instrumented fusion

• operated with a standard laminectomy with removing of the posterior midline structures or operated without magnifying devices was excluded from the micro-decompression group

Related Conditions & MeSH terms

• Degenerative Lumbar Spondylolisthesis
• Spinal Stenosis
• Spondylolisthesis

Intervention

Procedure:
• Micro-decompression alone
In surgical treatment of Degenerative Spondylolisthesis patients are operated on with a midline-precerving decompression without fusion
• Decompression and instrumented fusion
In surgical treatment of Degenerative Spondylolisthesis patients are operated on with a decompression followed by an instrumental fusion with or without an additional cage

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital of North Norway	Haukeland University Hospital, The Royal Norwegian Ministry of Health

References & Publications (6)

Austevoll IM, Gjestad R, Solberg T, Storheim K, Brox JI, Hermansen E, Rekeland F, Indrekvam K, Hellum C. Comparative Effectiveness of Microdecompression Alone vs Decompression Plus Instrumented Fusion in Lumbar Degenerative Spondylolisthesis. JAMA Netw Open. 2020 Sep 1;3(9):e2015015. doi: 10.1001/jamanetworkopen.2020.15015. — View Citation

Austevoll IM, Hermansen E, Fagerland MW, Storheim K, Brox JI, Solberg T, Rekeland F, Franssen E, Weber C, Brisby H, Grundnes O, Algaard KRH, Boker T, Banitalebi H, Indrekvam K, Hellum C; NORDSTEN-DS Investigators. Decompression with or without Fusion in Degenerative Lumbar Spondylolisthesis. N Engl J Med. 2021 Aug 5;385(6):526-538. doi: 10.1056/NEJMoa2100990. — View Citation

Bridwell KH, Sedgewick TA, O'Brien MF, Lenke LG, Baldus C. The role of fusion and instrumentation in the treatment of degenerative spondylolisthesis with spinal stenosis. J Spinal Disord. 1993 Dec;6(6):461-72. doi: 10.1097/00002517-199306060-00001. — View Citation

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 Apr 14;374(15):1413-23. doi: 10.1056/NEJMoa1513721. — View Citation

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 Apr 14;374(15):1424-34. doi: 10.1056/NEJMoa1508788. — View Citation

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 Jul;73(6):802-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	First reoperation	A new operation in the lumbosacral spine (excluding surgery for tumor and trauma) during follow up, occurring more than 90 days after index surgery is defined as reoperation.	From date of index operation (2007-2015) until end of follow up August 31st 2023
Secondary	Reoperations within 90 days	Reoperations within 90 days after index operation. This is reported separately since early reoperations are categorized as complications in the NORspine	From date of index operation (2007-2015) until 90 days after index surgery
Secondary	Other complications	Complications related to index operation reported in NORspine. Surgeon and patient reported. e.g dural tear, postoperative haematoma, surgical site infection, thromboembolism (DVT, LE), pneumonia	Reported at baseline and 3 months after the index operation