Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04544683 |
| Other study ID # |
IRB 116040 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
October 23, 2018 |
| Est. completion date |
December 7, 2023 |
Study information
| Verified date |
March 2024 |
| Source |
University of Utah |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Study Purpose:
This study is intended to monitor outcomes for 1 year following cervical TFESI. Based on
current clinic volume and enrollment rates into a current study of cervical epidural
injections that is nearing completion, we conservatively estimate a study enrollment period
of 18 months and a total period of 2.5 years from enrollment to final follow-up data
collection. If the study were to theoretically start enrolling in July 2019, we would
anticipate completion by February 2022.
Objectives:
1. Determine the proportion of patients with an 80% or greater improvement in arm and neck
numerical rating scale pain (NRS) score following an initial cervical transforaminal
steroid injection (TFESI) at 4 weeks post-injection and the duration of response up to
12 months.
2. Determine the proportion of patients with a 50%-79% improvement in arm and neck NRS
score following an initial cervical TFESI at 4 weeks post-injection and the duration of
response up to 12 months.
3. Determine the proportion of patients with less than 50% improvement in arm and neck NRS
score following an initial cervical TFESI at 4 weeks post-injection and the duration of
response up to 12 months.
4. Determine the proportion of patients with an initial injection plus up to 3 additional
injections that maintain 80% or greater, as well as 50-79%, improvement in arm and neck
NRS score for up to 12 months.
5. Determine the proportion of patients with a clinically significant change in function
defined by a minimally clinically significant change (MCIC) (≥10 point improvement ) or
30% improvement in Neck Disability Index (NDI) score following an initial cervical TFESI
at 4 weeks post-injection and the duration of response up to 12 months.
6. Determine the proportion of patients with clinically significant improvement in the
Medication Quantification Scale (MQS III) score (≥6.8 point change , equivalent to 10
oral morphine equivalents ) following an initial cervical TFESI at 4 weeks
post-injection and the duration of response up to 12 months.
6. Determine the proportion of patients with clinically significant improvement in the
categorical EuroQol 5 Dimensions tool (EQ-5D) defined by ≥0.03 following an initial cervical
TFESI at 4 weeks post-injection and the duration of response up to 12 months.
7. Compare patient demographic, clinical, and imaging characteristics between response groups
and perform predictive modeling to better understand variables that increase the likelihood
of a successful clinical outcome.
8. Report adverse effects.
Description:
Background and Project Justification: Neck pain is now the fourth leading cause of years lost
to disability, shortly after back pain, depression, and arthralgia. Cervical radiculopathy, a
common cause of neck and radiating arm pain, is estimated to afflict 83:100,000 individuals
yearly. Age-related cervical spondylosis and disc herniation are the most common causes, with
the C6 and C7 nerve roots most frequently affected. In general, patients who experience new
onset radicular pain tend to improve within 4-6 months, with complete recovery in over 80% of
patients by 24-36 months. However, a significant proportion of patients experience severe
pain and associated functional impairment despite conservative care, which often prompts
physician directed interventions.
Cervical transforaminal epidural steroid injection (TFESI) is a target-specific treatment for
refractory radicular pain. Analgesic mechanisms for epidural steroid administration include
reducing inflammation at the nerve root, reducing nociceptive input from somatic nerves,
stabilization of neural membranes, and blockade of C fiber activity in the dorsal root
ganglion . Previously, this procedure was associated with rare but catastrophic neurologic
injury, though to be related to inadvertent deposit of particulate steroid into the vertebral
artery or radiculomedullary arteries, both of which traverse through or close to the cervical
neuroforamina . Since the physician community has adopted new guidelines that include the use
of only non-particulate steroid during cervical TFESI , neurologic infarction has not been
reported in the literature. When the Spine Intervention Society (SIS) clinical practice
guidelines are employed, large cohort study demonstrates zero prevalence of serious
complications associated with this procedure .
While high-quality outcome literature demonstrates both efficacy and effectiveness for
analogous use of this intervention in the lumbar spine, far fewer studies have addressed
clinical outcomes associated with cervical TFESI in which appropriate procedure technique ,
outcome measurement, data analysis, and results interpretation have been reported . Outcome
literature reporting on the use of cervical TFESI is limited by small sample size,
retrospective design with loss of follow-up, lack of categorical data analysis, and a failure
to stratify results by demographic and clinical variables that potentially influence pain and
functional outcomes. Further, outcome literature reports on the effect of particulate steroid
injectate during cervical TFESI is no longer relevant to appropriate clinical practice in the
context of unequivocal guidelines. Pragmatic studies with a cervical TFESI arm in which
dexamethasone was use do allow for some insight regarding success rates associated with this
procedure; calculates of success rates in these studies arms demonstrate responder rates of
60% achieving >50% pain relief (CI95 35-85%) at 4 weeks, 55% achieving >50% (CI95 43-67%) at
8 weeks, and 65% achieving >50% at 12 weeks (CI95 48-81%). These responder rates are
encouraging, but limited by wide 95% confidence intervals due to small sample size. Prior
systematic review has concluded that the evidence for treatment benefit of radicular pain by
cervical TFESI is of very low quality due to multiple limitations in study design introducing
risk of bias, but does overall suggest approximately 50% patients experience 50% relief of
radicular pain for at least 4 weeks after cervical TFESI.
Additional clinical outcome literature is needed, particularly given recent policy decisions,
such as that of Oregon State in relation to ending coverage of epidural steroid injections at
any spinal level. Without expansion of the evidence-basis for this important procedure, there
is a risk that this treatment option may be taken away from patients suffering from cervical
radicular pain by further policy change. A sham-controlled trial, similar to the Ghahreman
study, would be ideal; however, due to cost considerations germane to a study designed and
conducted in a manner that would prevent any possible criticism from the larger medical
community, we instead propose a high-quality, large prospective cohort study as a significant
contribution to the literature. Even the best designed trials, such as Dreyfuss' 2006 study,
have been underpowered to definitively demonstrate effectiveness; notably, the lower bound of
the 95% confidence interval of the proportion of treatment responders in this study was 35%.
The investigators aim to conduct a large enough cohort study narrow the 95% confidence
interval of the proportion of responders substantially. Preliminary data from our center
demonstrates a responder rate of 55% at 4-week follow-up (n=22), based on a definition of
≥50% improvement in index pain (Appendix A). These data represent analysis of consecutive
patients who underwent cervical TFESI for unilateral radicular pain as a part of a different
prospective outcome study at our center, nearing completion. This responder rate represents a
conservative estimate of what might be expected in the proposed work, as the current study
includes less stringent inclusion and exclusion criteria.
Further, the investigators intend to use the results of this study as foundational data from
which to propose a randomized controlled study through a large federal funding mechanism. It
is imperative that such a trial be conducted by investigators who are experienced with this
procedure and understand the appropriate standards for the design and interpretation of the
results of a study of a treatment intervention for pain. Our spine research group is
well-positioned for this, and we absolutely welcome the input and mentorship of the Spine
Intervention Society Research Division, Board of Directors, and other leadership towards this
mutual goal.
