Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03469791 |
| Other study ID # |
2014/344 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2007 |
| Est. completion date |
December 31, 2027 |
Study information
| Verified date |
August 2022 |
| Source |
Haukeland University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In many countries a majority of patients with degenerative spondylolisthesis are operated on
with decompression plus instrumented fusion, but the scientific evidence for adding fusion is
controversial. To evaluate whether micro-decompression alone is as good as (non-inferior to)
decompression plus instrumented fusion, a study with data from the Norwegian Registry for
Spine Surgery was conducted, now the long-term follow up.
Description:
It is moderate evidence for that surgical treatment is superior non-surgical treatment for
Degenerative Spondylolisthesis (DS). Question regarding the effectiveness of different
surgical treatment alternatives is a controversy. The main goal for an operation is to
decompress the stenotic neural elements. Based on two influential studies in the early1990's,
an additional fusion procedure became more and more common and during the next decades the
rate of fusion procedures as well as the complexity of the fusion procedures increased
dramatically. In 2011 about 90 % of the surgeries performed in the United States included an
instrumented fusion procedure. This practice has been supported by several guidelines and
reviews. However, the evidence for this practice has been questioned and as a consequence of
the conflicting results from two randomised controlled trial, the role of fusion again has
become controversial.
According to the annual reports from Norwegian Spine Registry (NORspine), the majority of the
decompression alone surgeries for DS is performed with preserving of the midline structures.
These procedures are considered to be biomechanical less extensive and may result in less
instability and less progression of the slip compared to a standard laminectomy.
In the now published Norwegian study (NORSTEN-DS; Clinicaltrial.gov Identifier: NCT02051374)
DS the participants were randomised into micro-decompression alone and decompression plus
instrumented fusion. In the observational non-inferiority cohort study the investigators
evaluated the effectiveness of micro-decompression alone and decompression plus instrumented
fusion among patients registered in the NORspine registry. The hypothesis was that the
clinical result for the micro- decompression group is as good as the results for the
instrumented fusion group, at short time (12 months after operation) and at long time (7 to
15 years after operation) for DS .
Statistics For the complete cohort of patients fulfilling the inclusion and exclusion
criteria, the baseline demographics and outcome measures will be presented.
To as best as possible adjust for covariate that can bias the allocation to treatment,
Propensity score matching (PSM) will be used to make the distribution of observed baseline
patient characteristics in the micro-decompression group and the fusion group as similar as
possible. The following parameters will be included in the calaculation of the propensity
score: Age; Gender; American Society of Anesthesiologists (ASA) grade; Body Mass Index (BMI);
Smoking, Oswestry Disability Index(ODI), Numeric Rating Scale for leg pain and for back pain,
Euroqol 5-D (EQ5D), foraminal stenosis, degenerative disc disease, predominating back pain,
number of levels operated on and neurological palsy. The PSM scores will be derived from a
logistic regression model and reflect a patient's theoretical baseline probability for being
instrumentally fused. Using the technique of '1:1 matching without replacement', pairs of
fused and non-fused patients with a difference in propensity scores less than 0.2 in logit of
the standard deviation will be formed.
In order to include data from all three time points and hence make use of all available data,
Latent Growth Curve (LGC) models with Full Information Maximum Likelihood will be used for
estimating the change scores and the follow-up scores for ODI ,NRS leg pain and NRS back
pain. Thus, information from patients will not be excluded if data are missing at one of the
follow-ups. Statistical Package for the Social Sciences (SPSS) version 24 will be used for
descriptive statistics, tests for distribution of data, cross-tabulations with χ2 test,
Student t-tests and Mann-Whitney U tests of group differences and linear and logistic
regression modelling Mplus verion 7.3 will be used for analysing LGC models.
To control for biased estimate due to data missingness, a sensitivity analysis will be
performed. With use of baseline and follow-up data as predictors for multiple imputation
(MI), 10 data sets will be generated with complete follow-up scores for ODI, NRS leg pain and
NRS back pain.
The sample size calculation for comparing the effectiveness of the treatments is based on the
same assumption as the randomized multicentre trial on the same patient group
(ClinicalTrials.gov Identifier: NCT02051374). In a non-inferiority design, with one sided
testing, the investigators want to detect whether the responder rate for the
micro-decompression group is less than 15 percentages lower than for the fusion group. This
has to be tested by forming a 95% confidence interval (CI) for the difference of proportions
(i.e. percentage of responders in the fusion group minus percentage of responders in the
micro-decompression group) and has to be rejected if the upper limit of the CI is less than
15. If rejected, the conclusion will be that decompression alone is non-inferior, i.e. as
good as, decompression with fusion. A 15% difference in responder rate corresponds to a
number needed to treat of 7 patients (NNT = 100/15 = 6.67 [12]. Choosing a type 1 error =
0.05 and power = 0.90 gives a sample size of 160. Considering these assumptions, and adding
25% for possible dropouts, a total of 213 patients are required in each group.
To investigate the long term results, we will perform a similar study with data at long term
follow-up (5 to 15 years postoperatively) including the same patients as in the primary study
(one year follow-up). The patients will receive a similar questionnaire as used in the
primary study. The design, primary outcome, secondary outcomes, hypothesis, hypothesis
testing, non-inferiority margin and statistical methods will follow the same rules as for the
primary study. When analyzing the clinical outcomes (patient reported outcome measurements)
the statistician will be blinded for treatment assignment.
