Clinical trial NCT04544683
Conditions: Cervical Radiculopathy Cervical Spondylosis Disk, Herniated
Keywords: Transforaminal Epidural Injection
Sponsor: University of Utah
Start date: 2018-10-23; Completion date: 2023-12-07
Enrollment: 33 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

Detailed 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.

Arms: arm 1: Participants who meet inclusion and exclusion criteria will be enrolled into the study after consenting to and before receiving a first cervical TFESI. The baseline examination and all baseline questionnaires will be completed within 2 weeks before the first cervical TFESI. Participants will be given a daily pain diary chart to record NRS and percentage improvement during the 1st month post-injection. Participants will be contacted in the 1st week post-injection with a standardized questionnaire about their symptoms and a reminder about the 4 week (+/- 1 week) post-injection follow up. Routine scheduled follow-up by clinic visit or telephone call will occur at 4 weeks (+/- 1 week), 8 weeks (+/- 2 weeks), 3 months (+/- 2 weeks), 6 months (+/- 1 month), and 12 months (+/- 1 month), at which times all follow-up measures will be obtained.
Interventions: intervention 1: Cervical Transforaminal Epidural Injection with dexamethasone sodium phosphate
Intervention descriptions: intervention 1: Transforaminal epidural steroid injection: Injection of 1 to 2 mL of 1% lidocaine to the skin and subcutaneous tissues, a 25-gauge spinal needle will be placed at the level and side of radicular pathology, based on clinical correlation of symptoms/signs and magnetic resonance imaging findings. Advancement to the appropriate target position in the neuroforamen will be performed under fluoroscopic guidance. Satisfactory target position achieved and confirmed in both anterior-posterior and oblique views, 0.5 to 1 mL of contrast will be injected under live fluoroscopic observation with or without digital subtraction angiography depending on suggestion of vascular uptake. Upon confirmation of a satisfactory epidural contrast pattern without vascular uptake, the injectate will be delivered: dexamethasone sodium phosphate 1mL (10mg/mL) and 0.5 ml of 1% preservative-free lidocaine (total volume 1.5 mL).

Protocol documents:
Prot_SAP_000.pdf: 
PI:  Zachary McCormick, MD 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the Treatment of Cervical Radicular Pain: A Prospective 
Cohort Study.    
Version:  3.0, 13SEP2022 
Page 1 of 13 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the 
Treatment of Cervical Radicular Pain: A Prospective Cohort Study.    
Primary Investigator: 
Zachary McCormick, MD 
Co-Investigator:  
Aaron Conger, DO 
Richard Kendall, DO 
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) score13,14 following an initial cervical TFESI at
4 weeks post-injection and the duration of response up to 1-2 months.
6. Determine the proportion of patients with clinically significant improvement in the
Medication Quantification Scale (MQS III) score15 (≥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.
7. Determine the proportion of patients with clinically significant improvement in the
categorical EuroQol 5 Dimensions tool (EQ-5D)16 defined by ≥0.03 following an initial
cervical TFESI at 4 weeks post-injection and the duration of response up to 12 months.
8. 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.
9. Report adverse effects.
Hypotheses:  
1. At least 50% of patients with cervical radicular pain will experience 50% or greater relief of
index pain at 1-month follow-up after cervical TFESI.
2. At least 50% of patients with cervical radicular pain will experience a clinically significant
improvement in function at 1-month follow-up after cervical TFESI.
3. At least 50% of patients with cervical radicular pain will experience a clinically significant
improvement in analgesic medication use at 1-month follow-up after cervical TFESI.
4. At least 50% of patients with cervical radicular pain will experience a clinically significant
improvement in health-related quality of life at 1-month follow-up after cervical TFESI.


PI:  Zachary McCormick, MD 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the Treatment of Cervical Radicular Pain: A Prospective 
Cohort Study.    
Version:  3.0, 13SEP2022 
 
Page 2 of 13 
 
 
Introduction 
Neck pain is now the fourth leading cause of years lost to disability, shortly after back pain, 
depression, and arthralgia.17 Cervical radiculopathy, a common cause of neck and radiating arm 
pain, is estimated to afflict 83:100,000 individuals yearly.1 Age-related cervical spondylosis and 
disc herniation are the most common causes, with the C6 and C7 nerve roots most frequently 
affected.18 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.2 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.3–7 
Previously, this procedure was associated with rare but catastrophic neurologic injury, thought 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.19,20 Since the physician community has adopted new guidelines that include the 
use of only non-particulate steroid during cervical TFESI12, neurologic infarction has not been 
reported in the literature. When the Spine Intervention Society (SIS) clinical practice guidelines 
are employed, large cohort studies have demonstrated zero prevalence of serious complications 
associated with this procedure21. 
 
While high-quality outcome literature demonstrates both efficacy and effectiveness for 
analogous use of this intervention in the lumbar spine22,23, far fewer studies have addressed 
clinical outcomes associated with cervical TFESI in which appropriate procedure technique24, 
outcome measurement, data analysis, and results interpretation have been reported25. Outcome 
literature reporting on the use of cervical TFESI is limited by small sample size9, retrospective 
design with loss of follow-up26, lack of categorical data analysis10, and a failure to stratify results 
by demographic and clinical variables that potentially influence pain and functional outcomes10. 
Further, outcome literature reports on the effect of particulate steroid injectate during cervical 
TFESI9,27 are no longer relevant to appropriate clinical practice in the context of unequivocal 
guidelines.12,28 Pragmatic studies with a cervical TFESI arm in which dexamethasone was used 
do allow for some insight regarding success rates associated with this procedure; studies report 
responder rates of 60% achieving >50% pain relief (CI95 35-85%) at 4 weeks9, 55% achieving  
>50% (CI95 43-67%) at 8 weeks10, and 65% achieving >50% at 12 weeks (CI95 48-81%).29 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.8  
 
Image guidance is commonly studied, with some investigators suggesting the use of ultrasound 
30,31(30, 31), or CT guidance32 (3), however fluoroscopic guidance with use of digital subtraction 


PI:  Zachary McCormick, MD 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the Treatment of Cervical Radicular Pain: A Prospective 
Cohort Study.    
Version:  3.0, 13SEP2022 
 
Page 3 of 13 
 
imaging (DSI) remains the gold standard imaging modality33,34 (4,5). In terms of needle 
approach, a few new studies have been published to suggest possible alternative approaches. 
These include a modified parasagittal interlaminar approach under CT guidance32 (3), 
parasagittal interlaminar approach under fluoroscopic guidance35 (6), and standard interlaminar 
approach with threaded catheter36 (7). None of these studies (including our own, ref. 36), has 
shown clinically significant benefit between approaches or significant safety differences. Further, 
multiple studies published prior to our original protocol submission have suggested that the route 
of delivery into the epidural space has little differential impact on the likelihood of clinically 
meaningful pain reduction and functional improvement37-39 (8–10).  
Several new studies have been published since 2018 which support the use of CTFESI for 
cervical radicular pain. In our own RCT we found clinically significant reductions in pain and 
improvement in function in those treated with cervical epidural steroid injections, with no 
significance between group differences depending on the route used (transforaminal versus 
interlaminar with catheter)36 (7). Specifically, 49.1% (95% CI 36.4–62.0%), 46.4% (95% CI 
33.8–59.6%), and 51.9% (95% CI 38.4–65.2%) of participants reported >50% pain relief at 1, 3, 
and 6 months after CTFESI. The majority of participants also reported feeling at least “much 
improved” at 6 months. There were no serious adverse effects or complications noted in this 
study. Another study published in 2020 showed a 60% responder rate at one month with 
similarly observed low levels of pain at 5 year follow up, likely evidencing the favorable natural 
history of cervical radicular pain40 (11). Another report of outcomes after CTFESI showed 
significant reductions in pain and high patient satisfaction at two years41 (12).  
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 
level12. 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 study23, 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%. We 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. 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. 
 
Adverse events have also been further studied. A recent study of events after 1753 CTFESIs 
showed only 6 self–“limited” adverse events which included 2 vasovagal episodes, 1 instance of 


PI:  Zachary McCormick, MD 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the Treatment of Cervical Radicular Pain: A Prospective 
Cohort Study.    
Version:  3.0, 13SEP2022 
 
Page 4 of 13 
 
localized urticaria, 1 episode of self-“limited” tachycardia, 1 episode of “light headedness” 
which resolved after 30 minutes, and one report of dysphagia that resolved after 30 minutes42 
(13). These rates are similar to that observed in very large (n= 52,935) prior studies of the safety 
of epidural steroid injections wherein serious procedure related complications occurred in only 
0.011% of procedures performed43 (14).  
 
Further, we 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 pain25,44,45. 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. 
 
Subjects 
A total of 117 subjects, aged 18-80 on the day of enrollment, will be recruited for participation in 
this study. Participants who meet inclusion and exclusion criteria listed below will be enrolled 
into the study after consenting to and before receiving a first cervical TFESI. 
  
De-identification 
All subjects will be assigned a unique alphanumeric identifier. No personally identifiable 
information will be used in the final database.  All data will be stored on a highly secure, password 
protected computer. 
 
Participant Recruitment 
Our intended subject demographic includes an active population between the ages of 18 and 80 
years on the day of enrollment.  Potential study participants will be identified from our research 
center’s interventional and surgical clinics, as well as the interventional treatment room schedule. 
Additionally, we intend to recruit participants through word-of-mouth and physician referral. 
Further recruiting will take place through the distribution of flyers to the Health Sciences 
Education Building, University of Utah Student Life Center,  University of Utah Orthopedic 
Center, University of Utah South Jordan Health Center, University of Utah Farmington Center, 
and the University of Utah hospital.  Upon first contact with the potential participant, the study 
coordinator or research associate will provide a basic description of the study and review inclusion 
and exclusion criteria, general health status, and past medical history. Chart review at this point 
will consist of looking at their physician’s diagnosis and MRI imaging results to make sure they 
meet inclusion and exclusion criteria.  Interested volunteers who qualify will be asked to report to 
the University of Utah Orthopedic Center, University of Utah South Jordan Health Center, or 
University of Utah Farmington Center.  Prior to screening procedures and after being informed of 
any potential risks involved in the study, volunteers will be asked to provide written, informed 
consent for study participation. 
 
 
 


PI:  Zachary McCormick, MD 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the Treatment of Cervical Radicular Pain: A Prospective 
Cohort Study.    
Version:  3.0, 13SEP2022 
 
Page 5 of 13 
 
Inclusion Criteria:  
1. Adult patients aged 18-80 capable of understanding and providing consent in English and 
capable of complying with the outcome instruments used.  
2. Arm pain or shoulder girdle pain/periscapular pain with or without neck pain with 
duration less than or equal to 6 months.  
3. 24 hour average numeric pain rating score (NRS) for arm pain or shoulder 
girdle/periscapular pain of at least 4/10 at baseline evaluation, with neck pain score not 
exceeding arm and/or shoulder girdle/periscapular pain score.  
4. MRI (or CT if MRI not available) shows either a one level cervical disc herniation, disc 
osteophyte complex or degenerative foraminal stenosis, corresponding in side and 
location with predominately unilateral radicular pain, with or without neurological 
deficits. MRI may show degenerative changes at other levels.  
5. Patient consents to treatment with epidural injection in a shared decision-making process 
with the treating physician. 
6. Pain duration of at least 6 weeks or more.   
 
Exclusion Criteria:  
1. Those receiving remuneration for their pain treatment (e.g., disability, worker’s 
compensation).  
2. Those involved in active litigation relevant to their pain.  
3. The patient is incarcerated.   
4. Neck pain is greater than arm pain or shoulder girdle/periscapular pain.  
5. Bilateral radicular signs/symptoms (< 90% laterality of pain intensity, or bilateral 
neurological signs).  
6. BMI>35.  
7. Prior epidural steroid injections for treatment of current episode. 
8. Those unable to read English and complete the assessment instruments.  
9. Spondylolisthesis at the involved or adjacent segments.  
10. Systemic inflammatory arthritis (e.g., rheumatoid, lupus).  
11. Addictive behavior, severe clinical depression, or psychotic features.   
12. Possible pregnancy or other reason that precludes the use of fluoroscopy.  
13. Treatment of infection with antibiotics within the past 7 days.  
14. Progressive motor deficit and/or clinical signs of myelopathy.  
15. History of prior cervical spine surgery.  
16. Medical conditions causing significant functional disability (e.g., stroke, COPD) 
 
 
Study design: Prospective cohort study 
 
Participants who meet inclusion and exclusion criteria will be enrolled into the study after 
consenting to and before receiving a first cervical TFESI. The baseline examination and all 
baseline questionnaires will be completed within 2 weeks before the first cervical TFESI. 
Routine scheduled follow-up by clinic visit or telephone call will occur at 4 weeks(+/- 1 month), 


PI:  Zachary McCormick, MD 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the Treatment of Cervical Radicular Pain: A Prospective 
Cohort Study.    
Version:  3.0, 13SEP2022 
 
Page 6 of 13 
 
3 months(+/- 1 month), 6 months(+/- 1 month), and 12 months(+/- 3 month), at which times all 
follow-up measures will be obtained.   
Primary Outcomes:   
The primary outcome is “treatment response” as defined by classification into one of the three 
following categories:  
1. 80% or greater improvement in index pain following an initial cervical transforaminal 
injection of steroid (TFESI) at 4 weeks post-injection, 3 months post-injection and 
response at 12 months.  
2. 50%-79% improvement in index pain following an initial cervical TFESI at 4 weeks 
post-injection, 3 months post-injection, and response 12 months.  
3. Less than 50% improvement in index pain following an initial cervical TFESI at 4 weeks 
post-injection, 3 months post-injection, and response at 12 months.  
  
Secondary Outcomes:   
1. Disability (NDI)  
2. Health-related quality of life (EQ-5D)  
3. Surgery  
4. Personal goal achievement  
5. Work status  
6. Analgesic use (MQS-III score15)   
7. Quantity and type of ancillary treatment  
8. Number of repeat injections 
9. Predictors of repeat injections from baseline physical and radiologic findings  
10. Predictors of overall response with injection treatment from baseline exam and radiologic 
findings  
11. Proportion of patients requiring more than one injection to reach the 80% improvement 
mark   
12. Differences in long term outcome between the single injection group and the >1 injection 
group in  
a. Need for surgery  
b. Return to work  
c. Personal goal achievement (from COMBI)  
d. Quality of life (EQ-5D) 
 
Power Analysis 
Dreyfuss et al.9 found that 60% of subjects who received a cervical TFESI with dexamethasone 
reported at least 50% improvement in NRS score (CI95 35-85%) at 4 weeks. In order to distinguish 
the lower bound of a 95% confidence interval from a theoretical placebo/sham response rate of 
30%, but also from less than a 50% responder rate (we suggest being the minimum acceptable to 
the medical community), a sample size of 105 subjects is necessary (95% CI 51-69%, assuming a 
60% responder rate). In order to account for a conservative 10% attrition rate by the 4-week 
primary endpoint, we propose to enroll 117 patients.   
 
Procedures 


PI:  Zachary McCormick, MD 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the Treatment of Cervical Radicular Pain: A Prospective 
Cohort Study.    
Version:  3.0, 13SEP2022 
 
Page 7 of 13 
 
During the injection procedure, per standard clinical practice, the participant will be positioned 
on a fluoroscopy table. A pre-procedure time-out will be performed, as is protocol in the 
University practice.  Using fluoroscopic guidance, cervical ESI will be performed (please note 
that the procedure specifications are provided as an example of the current clinical practice and 
minor variations in parameters are still considered standard of care and do not constitute protocol 
deviations): 
 
Transforaminal epidural steroid injection (As performed as standard of care practice) 
After injection of 1 to 2 mL of lidocaine to the skin and subcutaneous tissues, a 25-gauge spinal 
needle will be placed at the level and side of radicular pathology, based on clinical correlation of 
symptoms/signs and magnetic resonance imaging findings. Advancement to the appropriate 
target position in the neuroforamen will be performed under fluoroscopic guidance according to 
practice guidelines.44 Once a satisfactory target position is achieved and confirmed in both 
anterior-posterior and oblique views, 0.5 to 3 mL of iodinated contrast medium will be injected 
under live fluoroscopic observation with or without digital subtraction angiography depending 
on suggestion of vascular uptake, as is standard practice and recommended by practice 
guidelines.44 Upon confirmation of a satisfactory epidural contrast pattern without vascular 
uptake, 1mL (10mg/mL) of dexamethasone sodium phosphate mixed with lidocaine will be 
injected. After the injection procedure, participants will be observed and then discharged from 
the clinic with written discharge instructions (current standard practice). 
 
Repeat injections 
Participants who achieve 80% or more relief of their usual pain at the 4-week follow-up and who 
subsequently experience a recurrence of their usual index pain are offered a repeat procedure as 
per standard of care. “Usual pain” is defined as their cervical radicular pain (upper extremity 
pain or shoulder girdle/ periscapular pain) which is greater than axial neck pain. Participants with 
50-79% relief will be offered a second injection (at 4-week follow-up) with the goal of achieving 
greater than 80% relief. Responders will be offered a repeat injection if pain returns to the extent 
that warrants consideration of an additional injection. Duration of relief will be considered the 
time from the provision of the TFESI procedure until the participant reports a worsening of pain 
to the extent that warrants consideration of an additional injection. This may occur during an 
unscheduled follow-up, by phone correspondence, or as reported during scheduled follow-up or 
when a repeat TFESI is requested and performed.  
 
Data Collection: 
 
An electronic data collection system (REDCap via computer) will be used to record all pre-
procedure and follow-up data as listed above (See attached PDF for baseline survey): 
 
• At initial visit 
o Patient’s description of pain (characteristics of pain, e.g., burning, electric) and 
location of pain symptoms.  
o Demographics  
o Medical, surgical and psychiatric history  


PI:  Zachary McCormick, MD 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the Treatment of Cervical Radicular Pain: A Prospective 
Cohort Study.    
Version:  3.0, 13SEP2022 
 
Page 8 of 13 
 
o BMI  (calculated from patient reported weight and height) 
o Radiologic details relating to location and morphology of the cervical disc 
herniation, disc osteophyte complex, or degenerative foraminal stenosis if present.  
o Categorical EQ-5D Health Related Quality of Life questionnaire (EQ-5D)  
o Neck Disability Index (NDI)  
o Personal goal achievement (from COMBI) 
o Work history and current status 
o Current medication(s) collected in REDCap survey 
o Ancillary treatment log, of any treatment related to the underlying condition other 
than analgesic use (e.g., physical therapy, chiropractic care, acupuncture, ice or 
heat, home cervical traction)   
o Physical examination  
o Neurological examination 
o NRS for arm pain or shoulder girdle/ periscapular pain and separately, NRS for 
neck pain (24 hour average) at baseline. 
• Follow-up by clinic evaluation or standardized phone call survey 
o Date of initial injection (to be confirmed by EMR) 
o Number of repeat cervical TFESIs and dates (to be confirmed by EMR) 
o EQ-5D  
o Neck Disability Index (NDI)  
o Personal goal achievement (from COMBI) 
o Work history and current status 
o Current medication(s) collected in REDCap survey 
o Ancillary treatment log, of any treatment related to the underlying condition other 
than analgesic use (e.g., physical therapy, chiropractic care, acupuncture, ice or 
heat, home cervical traction)   
o Global perception of change 
o NRS for arm pain or shoulder girdle/ periscapular pain and separately, NRS for 
neck pain (24 hour average) 
 
Immediately after injection the following will be obtained: 
1) Fluoroscopy time  
2) Post-injection NRS pain score  
3) Adverse events, if they occurred 
 
Data Storage: 
Hard copy data will be collected and stored in a password-protected computer located in the 
Division of PM&R. Participants will each be assigned an ID number that will be used, along 
with their name, as the identifiers on any documents. Participant data will be compiled onto a 
single password protected file, where they will only be identified by their ID number. An 
enrollment log will be the only file where subject names are correlated with ID numbers. This 
will be kept in a separate, secure, password-protected file in the Division of PM&R. 
 
Data Analysis Plan 


PI:  Zachary McCormick, MD 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the Treatment of Cervical Radicular Pain: A Prospective 
Cohort Study.    
Version:  3.0, 13SEP2022 
 
Page 9 of 13 
 
The primary outcome will be the proportion of participants with 50% or greater reduction in 
neck and arm pain on the NRS pain score at the 1-month follow-up assessment. Secondary 
outcomes included reduction in median NRS pain score (both neck pain and arm pain), NDI-5, 
MQS III, opioid consumption in daily morphine equivalents, PGIC score, and satisfaction score. 
Secondary outcomes will also be defined based on categorical “responder analysis” definitions of 
important clinical change given the National Institutes of Health recommendation for responder 
analysis in the assessment of therapeutic spine pain interventions.45 The responder analysis will 
include the proportion of patients with 30% or greater improvement on the NDI-5,46,47 a PGIC 
score less than 3 (indicating “improved” or “very much improved”), a 6.8 or greater point 
reduction on the MQS III score (equivalent to approximately 10 daily morphine equivalents),48 
work status, number of repeat injections, and the proportion of participants who undergo surgical 
spine surgery. 
 
Statistical analysis 
Descriptive statistics (mean and SD for quantitative variables; frequency and proportion for 
categorical variables) will be calculated for patient demographics, along with the primary and 
secondary outcome variables listed above. A multilevel mixed-effects generalized linear model 
with ordinal family and logit link will be used to examine longitudinal changes in index pain 
following an initial cervical TFESI at 4 weeks, 3 months, and 12 months post-injection. 
Specifically, index pain will be categorized into three ordinal categories (≥ 80%, 50-79%, or < 
50% improvement), and will be used as an ordinal outcome variable, while three time points 
described here will be used as a time variable. Potential covariates  for the model will include: 1) 
age, 2) duration of pain, 3) baseline NDI score, 4) degree of nerve compression (grade 1, grade 2, 
grade 3, or grade 4), 5) work status (employed or unemployed), 6) DM2 (present or absent), 7) 
opioid use (yes or no), and 8) baseline NRS pain score separately for arm and neck. 
 
Risks/Benefits: 
Risks of study participation include the potential loss of confidentiality.  
 
Risks for standard of care procedure are the same as those for any standard fluoroscopically 
guided cervical ESI frequently performed in the PM&R Spine Clinic.  These include: local 
infection, epidural hematoma or abscess, dural puncture and potential post-dural puncture 
headache, paresthesia during needle placement, pain at the injection side, failure of technique, 
allergy to latex or medications being used.  Utilizing fluoroscopy, the risk of nerve damage, 
spinal cord injury or intravascular injection is less than 1:500,000. The length of stay and length 
of recovery is no longer than that of a standard ESI performed in the PM&R Spine Clinic at 
present.  
 
There are no direct benefits to the individual by participating in this study. The patients will be 
presented with the same options of treatment whether they enroll in the study or decide not to.  The 
information extracted from this study may provide the investigators a better understanding of 
patient’s pain response following a cervical epidural steroid injection. 
 
 
Study Termination Criteria 


PI:  Zachary McCormick, MD 
Title: The Effectiveness of Cervical Transforaminal Epidural Steroid Injection for the Treatment of Cervical Radicular Pain: A Prospective 
Cohort Study.    
Version:  3.0, 13SEP2022 
 
Page 10 of 13 
 
- 
Adverse events considered/identified by the medical staff during the procedure process 
- 
The subject requests to be withdrawn from the study during the procedure. 
 
 
Safety Monitoring Plan 
Safety will be monitored by all members of the study team: 
 
Zachary McCormick, MD 
Richard Kendall, DO 
Aaron Conger, DO 
 
The Principal Investigator is an MD at the University of Utah.  Members of the data and safety 
monitoring committee will be in close contact with all the subjects throughout the study, both in-
person and via telephone. The members of the data and safety monitoring committee will review 
potential side effects and adverse reactions with each subject at the time of delivery of the study 
drug and at the time of each sample collection. All the committee members are located at the 
University of Utah clinical locations; all members have research experience. 
 
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