Effectiveness of Cervical Transforaminal Epidural Steroid Injection

NCT ID: NCT04544683

Last Updated: 2024-04-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-23
• Study Completion Date: 2023-12-07

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.

Conditions

Cervical Radiculopathy; Cervical Spondylosis; Disk, Herniated

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Cervical Pain for 6 months or less and scheduled for TFESI

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.

Group Type: OTHER

Cervical Transforaminal Epidural Injection with dexamethasone sodium phosphate

Intervention Type: DRUG

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).

Interventions

Cervical Transforaminal Epidural Injection with dexamethasone sodium phosphate

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).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Adult patients aged 18-80 capable of understanding and providing consent in English and capable of complying with the outcome instruments used.
• Arm pain or shoulder girdle pain/periscapular pain with or without neck pain with duration less than or equal to 6 months.
• 3-day 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.
• 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.
• Patient consents to treatment with epidural injection in a shared decision-making process with the treating physician.
• Pain duration of at least 6 weeks or more.

Exclusion Criteria

• Those receiving remuneration for their pain treatment (e.g., disability, worker's compensation).
• Those involved in active litigation relevant to their pain.
• The patient is incarcerated.
• Neck pain is greater than arm pain or shoulder girdle/periscapular pain.
• Bilateral radicular signs/symptoms (< 90% laterality of pain intensity, or bilateral neurological signs).
• BMI>35.
• Prior epidural steroid injections for treatment of current episode.
• Those unable to read English and complete the assessment instruments.
• Spondylolisthesis at the involved or adjacent segments.
• Systemic inflammatory arthritis (e.g., rheumatoid, lupus).
• Addictive behavior, severe clinical depression, or psychotic features.
• Possible pregnancy or other reason that precludes the use of fluoroscopy.
• Treatment of infection with antibiotics within the past 7 days.
• Progressive motor deficit and/or clinical signs of myelopathy.
• History of prior cervical spine surgery.
• Medical conditions causing significant functional disability (e.g., stroke, COPD)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Zack McCormick

Zachary McCormick, MD FAAPMR, Associate Professor, Director of Clinical Spine Research, Director of Interventional Spine and Musculoskeletal Medicine Fellowship

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Utah

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB 116040

Identifier Type: -

Identifier Source: org_study_id