Low Back Pain, Radiating Pain
Conditions
Keywords
radiating back pain, epidural block, steroid, recurrent low back pain, Lumbar Epidural Steroid Block with 3 injections
Brief summary
Epidural injection will be completed under fluoroscopy and all patients will receive 1-4 mg of Midazolam for relaxation before procedure and, if needed, 50-100 mcg of Fentanyl intravenous (IV). Radiopaque contrast (Omnipaque 300), for confirming the epidural position of the needle, steroids and local anesthetic agents will be used according to the physician performing the block and will not be controlled by the study. Patients will be randomly assigned to receive either inhaled Entonox along with the interventional block they are scheduled for or oxygen. They will be blinded about the treatment they are receiving. Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery. Those randomized to the oxygen group will receive oxygen through a similar mouthpiece for the entire duration of the procedure and recovery for 4 hours. Following completion of procedure the patient will be transferred to recovery and monitored for 3-5 hours then discharged home with instructions. Possible side effects will be monitored and recorded, pain score of patient will be recorded before discharge. All the patients will receive standard instructions regarding physical back exercises. This will be repeated for every procedure up to maximum of three blocks. The patients will be followed during each block and over a period of 1, 3, 6 and 12 months and on each follow-up visit will complete computerized set of questionnaires as they did before the procedure. The patients charts will be then reviewed for one year after the initial procedure to determine if further epidural steroid injections or surgery for the presenting problem were required. It is anticipated that the appropriate number of patients will be enrolled within six months of study initiation.
Interventions
OTHEREntonox
Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
OTHEROxygen
Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery.
Sponsors
The Cleveland Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 18 to 80 years old at time of the first procedure * Male or female * History of chronic low back pain for longer than 6 months due to radiculopathy, symptomatic spinal canal stenosis, disc prolapse, postlaminectomy syndrome * magnetic resonance imaging or electromyographic evidence of nerve root damage * Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score of \>12 * No or minimal evidence of facet joint pathology
Exclusion criteria
* Known contraindications for epidural injection * Patients with ongoing workers' compensation claims * unstable or heavy opioid use (400 mg of morphine equivalents daily), * psychiatric disorders * medical illness, including conditions that could interfere with the interpretation of the outcome assessments * pregnant or lactating women * Current or recent drug abuse (within past 6 months). * Patient refuses regional analgesia. * Alcohol or drug abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in VAS Pain Score From Baseline to 3 Month Follow-up | At baseline (before 1st block) and 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks) | 10-cm-long Visual Analog Scale (VAS) pain score, ranges from 0 (no pain) to 10 (worst pain imaginable). It was measured before 1st 2nd and 3rd block and at 3 month follow-up. The primary outcome was the change in VAS pain score from baseline (before 1st block) to the 3 month follow-up. |
| Change in VAS Pain Score From Baseline to Before 2nd Block | At baseline (before 1st block) and before the 2nd block, typically at 1 month from baseline | 10-cm-long Visual Analog Scale (VAS) pain score, ranges from 0 (no pain) to 10 (worst pain imaginable). It was measured before 1st 2nd and 3rd block and at 3 month follow-up. The primary outcome was the change in VAS pain score from baseline (before 1st block) to before the 2nd block. |
| Change in VAS Pain Score From Baseline to Before 3rd Block | At baseline (before 1st block) and before the 3rd block, typically at 2 months from baseline | 10-cm-long Visual Analog Scale (VAS) pain score, ranges from 0 (no pain) to 10 (worst pain imaginable). It was measured before 1st 2nd and 3rd block and at 3 month follow-up. The primary outcome was the change in VAS pain score from baseline (before 1st block) to before the 3rd block |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Usage of Opioids | 2nd block, typically at 1 month from baseline | — |
| Change in Oswestry Score (% of Disability) From Baseline to 2nd Block | At baseline (before 1st block) and before the 2nd block, typically at 1 month from baseline | Oswestry score ranges from 0% to 100%, which measures % of disability. The outcome is change in the Oswestry score from baseline (before 1st block) to before 2nd block. |
| Biomarkers | baseline - before 1st block | BIOMARKERS: IL-1β, IL-6, IL-10, 1L-17A, IFN-γ, and TNF-α |
| Usage of Opioid | 3rd block, typically at 2 months from baseline | — |
| Change in Oswestry Score (% of Disability) From Baseline to 3rd Block | At baseline (before 1st block) and before the 3rd block, typically at 2 months from baseline | Oswestry score ranges from 0% to 100%, which measures % of disability. The outcome is change in the Oswestry score from baseline (before 1st block) to before 3rd block. |
| Change in Oswestry Score (% of Disability) From Baseline to 3 Months Follow-up | At baseline (before 1st block) and 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks) | Oswestry score ranges from 0% to 100%, which measures % of disability. The outcome is change in the Oswestry score from baseline (before 1st block) to 3 months follow-up. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entonox Patients will receive inhaled Entonox along with the interventional block they are scheduled.
Entonox: Those randomized to Entonox will inhale the gas through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery. | 39 |
| Oxygen Patients will receive inhaled oxygen along with the interventional block they are scheduled.
Oxygen: Those randomized to oxygen will inhale it through a mouthpiece throughout the procedure and also continue to receive it for a total of 4 hours in the recovery. | 39 |
| Total | 78 |
Baseline characteristics
| Characteristic | Entonox | Oxygen | Total |
|---|---|---|---|
| Age, Continuous | 70 years STANDARD_DEVIATION 20 | 73 years STANDARD_DEVIATION 16 | 71 years STANDARD_DEVIATION 18 |
| American Society of Anesthesiologists physical status I: A normal healthy patient | 9 participants | 7 participants | 16 participants |
| American Society of Anesthesiologists physical status II: A patient with mild systemic disease | 30 participants | 27 participants | 57 participants |
| American Society of Anesthesiologists physical status III: A patient with severe systemic disease | 0 participants | 5 participants | 5 participants |
| Body mass index | 30 kg/m2 | 28 kg/m2 | 30 kg/m2 |
| Race/Ethnicity, Customized African American | 12 participants | 12 participants | 24 participants |
| Race/Ethnicity, Customized Caucasian | 27 participants | 27 participants | 54 participants |
| Sex: Female, Male Female | 17 Participants | 21 Participants | 38 Participants |
| Sex: Female, Male Male | 22 Participants | 18 Participants | 40 Participants |
| Smoking status Current Smoker | 10 participants | 9 participants | 19 participants |
| Smoking status Never smoked | 14 participants | 18 participants | 32 participants |
| Smoking status Previously quit | 15 participants | 12 participants | 27 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 39 | 0 / 39 |
| serious Total, serious adverse events | 0 / 39 | 0 / 39 |
Outcome results
Primary
Change in VAS Pain Score From Baseline to 3 Month Follow-up
10-cm-long Visual Analog Scale (VAS) pain score, ranges from 0 (no pain) to 10 (worst pain imaginable). It was measured before 1st 2nd and 3rd block and at 3 month follow-up. The primary outcome was the change in VAS pain score from baseline (before 1st block) to the 3 month follow-up.
Time frame: At baseline (before 1st block) and 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks)
Population: For 10 patients with missing VAS at 3 month follow up: 5 patients who had 2nd or 3rd epidural block, we assigned the last VAS observation (i.e., from VAS before 2nd or 3rd block to 3 month follow-up); and for 5 patients who only had 1st epidural, we assigned the worst VAS (10) for Entonox patients and the best VAS (0) for Oxygen patients.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entonox | Change in VAS Pain Score From Baseline to 3 Month Follow-up | -1.6 units on a scale | Standard Deviation 3 |
| Oxygen | Change in VAS Pain Score From Baseline to 3 Month Follow-up | -1.2 units on a scale | Standard Deviation 2.6 |
p-value: 0.8495% CI: [-1.43, 1.17]Regression, Linear
p-value: 0.1295% CI: [-2.34, 0.28]Regression, Linear
Primary
Change in VAS Pain Score From Baseline to Before 2nd Block
10-cm-long Visual Analog Scale (VAS) pain score, ranges from 0 (no pain) to 10 (worst pain imaginable). It was measured before 1st 2nd and 3rd block and at 3 month follow-up. The primary outcome was the change in VAS pain score from baseline (before 1st block) to before the 2nd block.
Time frame: At baseline (before 1st block) and before the 2nd block, typically at 1 month from baseline
Population: 10 patients in the Entonox group and 11 patients in the Oxygen group did not receive the 2nd block treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entonox | Change in VAS Pain Score From Baseline to Before 2nd Block | -0.6 units on a scale | Standard Deviation 1.7 |
| Oxygen | Change in VAS Pain Score From Baseline to Before 2nd Block | -0.4 units on a scale | Standard Deviation 2.1 |
p-value: 0.6398.3% CI: [-1.8, 1.21]Mixed Models Analysis
Primary
Change in VAS Pain Score From Baseline to Before 3rd Block
10-cm-long Visual Analog Scale (VAS) pain score, ranges from 0 (no pain) to 10 (worst pain imaginable). It was measured before 1st 2nd and 3rd block and at 3 month follow-up. The primary outcome was the change in VAS pain score from baseline (before 1st block) to before the 3rd block
Time frame: At baseline (before 1st block) and before the 3rd block, typically at 2 months from baseline
Population: 21 patients in the Entonox group and 26 patients in the Oxygen group did not receive the 2nd block treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entonox | Change in VAS Pain Score From Baseline to Before 3rd Block | -2.1 units on a scale | Standard Deviation 3 |
| Oxygen | Change in VAS Pain Score From Baseline to Before 3rd Block | -0.5 units on a scale | Standard Deviation 2.2 |
p-value: 0.1698.3% CI: [-3.05, 0.82]Mixed Models Analysis
Secondary
Biomarkers
BIOMARKERS: IL-1β, IL-6, IL-10, 1L-17A, IFN-γ, and TNF-α
Time frame: before 3rd block, typically at 2 months from baseline
Population: 21 Entonox patients and 26 Oxygen patients did come for the 3rd block. Among the patients who came for the 3rd block, blood sample was not collected in 5 Entonox patients and 1 Oxygen patient.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Entonox | Biomarkers | IL-6 | 110 pg/ml |
| Entonox | Biomarkers | IL-17A | 153 pg/ml |
| Entonox | Biomarkers | IL-1β | 120 pg/ml |
| Entonox | Biomarkers | IFN-γ | 97 pg/ml |
| Entonox | Biomarkers | TNF-α | 5 pg/ml |
| Entonox | Biomarkers | IL-10 | 170 pg/ml |
| Oxygen | Biomarkers | TNF-α | 11 pg/ml |
| Oxygen | Biomarkers | IL-1β | 113 pg/ml |
| Oxygen | Biomarkers | IL-6 | 239 pg/ml |
| Oxygen | Biomarkers | IL-10 | 244 pg/ml |
| Oxygen | Biomarkers | IL-17A | 140 pg/ml |
| Oxygen | Biomarkers | IFN-γ | 88 pg/ml |
Secondary
Biomarkers
BIOMARKERS: IL-1β, IL-6, IL-10, 1L-17A, IFN-γ, and TNF-α
Time frame: 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks)
Population: No blood sample was planned to be collected.
Secondary
Biomarkers
BIOMARKERS: IL-1β, IL-6, IL-10, 1L-17A, IFN-γ, and TNF-α
Time frame: baseline - before 1st block
Population: Blood sample was not collected for 5 Entonox patients and 1 Oxygen patients.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Entonox | Biomarkers | IL-1β | 206 pg/ml |
| Entonox | Biomarkers | IL-6 | 226 pg/ml |
| Entonox | Biomarkers | IL-10 | 174 pg/ml |
| Entonox | Biomarkers | IL-17A | 146 pg/ml |
| Entonox | Biomarkers | IFN-γ | 93 pg/ml |
| Entonox | Biomarkers | TNF-α | 13 pg/ml |
| Oxygen | Biomarkers | IFN-γ | 85 pg/ml |
| Oxygen | Biomarkers | IL-1β | 140 pg/ml |
| Oxygen | Biomarkers | IL-17A | 137 pg/ml |
| Oxygen | Biomarkers | IL-6 | 198 pg/ml |
| Oxygen | Biomarkers | TNF-α | 9 pg/ml |
| Oxygen | Biomarkers | IL-10 | 176 pg/ml |
Secondary
Biomarkers
BIOMARKERS: IL-1β, IL-6, IL-10, 1L-17A, IFN-γ, and TNF-α
Time frame: before 2nd block, typically at 1 month from baseline
Population: 10 Entonox patients and 11 Oxygen patients did not come for 2nd block. Among patients came for the 2nd block, blood sample was not collected in 9 Entonox patients and 6 Oxygen patients.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Entonox | Biomarkers | IL-1β | 128 pg/ml |
| Entonox | Biomarkers | IL-6 | 224 pg/ml |
| Entonox | Biomarkers | IL-10 | 142 pg/ml |
| Entonox | Biomarkers | IL-17A | 146 pg/ml |
| Entonox | Biomarkers | IFN-γ | 124 pg/ml |
| Entonox | Biomarkers | TNF-α | 10 pg/ml |
| Oxygen | Biomarkers | IFN-γ | 79 pg/ml |
| Oxygen | Biomarkers | IL-1β | 100 pg/ml |
| Oxygen | Biomarkers | IL-17A | 128 pg/ml |
| Oxygen | Biomarkers | IL-6 | 127 pg/ml |
| Oxygen | Biomarkers | TNF-α | 10 pg/ml |
| Oxygen | Biomarkers | IL-10 | 163 pg/ml |
Secondary
Change in Oswestry Score (% of Disability) From Baseline to 2nd Block
Oswestry score ranges from 0% to 100%, which measures % of disability. The outcome is change in the Oswestry score from baseline (before 1st block) to before 2nd block.
Time frame: At baseline (before 1st block) and before the 2nd block, typically at 1 month from baseline
Population: 10 Entonox patients and 11 Oxygen patients did not receive 2nd block.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entonox | Change in Oswestry Score (% of Disability) From Baseline to 2nd Block | -7 absolute percentage | Standard Deviation 14 |
| Oxygen | Change in Oswestry Score (% of Disability) From Baseline to 2nd Block | -6 absolute percentage | Standard Deviation 14 |
Secondary
Change in Oswestry Score (% of Disability) From Baseline to 3 Months Follow-up
Oswestry score ranges from 0% to 100%, which measures % of disability. The outcome is change in the Oswestry score from baseline (before 1st block) to 3 months follow-up.
Time frame: At baseline (before 1st block) and 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks)
Population: 5 patients in each group were lost follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entonox | Change in Oswestry Score (% of Disability) From Baseline to 3 Months Follow-up | -11 absolute percentage | Standard Deviation 19 |
| Oxygen | Change in Oswestry Score (% of Disability) From Baseline to 3 Months Follow-up | -6 absolute percentage | Standard Deviation 21 |
Secondary
Change in Oswestry Score (% of Disability) From Baseline to 3rd Block
Oswestry score ranges from 0% to 100%, which measures % of disability. The outcome is change in the Oswestry score from baseline (before 1st block) to before 3rd block.
Time frame: At baseline (before 1st block) and before the 3rd block, typically at 2 months from baseline
Population: 21 Entonox patients and 26 Oxygen patients did not receive 3rd block.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Entonox | Change in Oswestry Score (% of Disability) From Baseline to 3rd Block | -10 absolute percentage | Standard Deviation 13 |
| Oxygen | Change in Oswestry Score (% of Disability) From Baseline to 3rd Block | -7 absolute percentage | Standard Deviation 18 |
Secondary
Usage of Opioid
Time frame: 3rd block, typically at 2 months from baseline
Population: 21 Entonox patients and 26 Oxygen patients did not receive 2nd block.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entonox | Usage of Opioid | 3 participants |
| Oxygen | Usage of Opioid | 2 participants |
Secondary
Usage of Opioid
Time frame: 3 months follow-up after last block (maximum of 3 blocks with a typical 1 month interval between blocks)
Population: 5 patients in each group were lost follow up.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entonox | Usage of Opioid | 6 participants |
| Oxygen | Usage of Opioid | 9 participants |
Secondary
Usage of Opioids
Time frame: 2nd block, typically at 1 month from baseline
Population: 10 Entonox patients and 11 Oxygen patients did not receive 2nd block.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Entonox | Usage of Opioids | 3 participants |
| Oxygen | Usage of Opioids | 7 participants |