Pulsed Epidural Radiofrequency Versus Epidural Steroid Injection in Patients With Failed Back Syndrome
Phase: NA
Conditions: Persistent Spinal Pain Syndrome Type II, Failed Back Surgery Syndrome, Chronic Low Back Pain, Post-Laminectomy Syndrome
Sponsor: Puerta de Hierro University Hospital

 
 
 
 
 
 
 
CLINICAL INVESTIGATION PROTOCOL 
Title: 
“Epidural Pulsed Radiofrequency versus Epidural Steroids Injection for Treatment of 
Failed Back Syndrome: A Prospective, Randomized, Single-Blind and Multicenter 
Study” 
 
Protocol Code: 
EPIPUL 
 
Sponsor: 
Fundación Investigación HM Hospitales 
Hospital Universitario HM Sanchinarro 
 
Coordinating Investigator: 
Dr. Agustín Mendiola de la Osa 
Hospital Universitario HM Sanchinarro 
 
Revisions: 
Version 
Date 
Description 
1.1 
25th of March 2019 
First revision and approval 
1.2 
18th of July 2019 
Second revision and approval 
1.3 
26th of November 2019 
Third revision and approval 
1.4 
11 th of February 2020 
Fourth revision and approval 
 
CONFIDENTIAL: The information and data included in this protocol is property of the Sponsor. No person is authorized to 
make such information public without the written permission of the Sponsor. These restrictions will also apply to all 
information that is provided to you in the future and that is considered privileged or confidential. This material may be 
disclosed and used by your team and associates, insofar as it may be necessary for the development of clinical research.

 
 
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Epidural Pulsed Radiofrequency versus Epidural Steroids Injection for Treatment of 
Failed Back Syndrome: A Prospective, Randomized, Single-Blind and Multicenter Study 
CONFIDENTIAL 
SIGNATURE PAGE 
Principal Investigator Signature  
“I have read this clinical investigation plan and agree to participate in the clinical investigation by 
Fundación Investigación HM Hospitales. I agree to conduct this investigation according to the 
requirements of the clinical investigation plan and in accordance with the Declaration of Helsinki, ISO 
14155-2011, EU and local regulations and conditions imposed by the reviewing Ethics Committee. I 
agree to supervise all Sub-Investigators at my site as well as the use of all of the devices at my 
institution and to ensure appropriate informed consent is obtained from all subjects prior to inclusion 
in this study”. 
 
Name of Principal Investigator: ________________________________ 
 
________________________ 
 
 
_____ /_____ /_________ 
Signature 
 
 
 
 
 
Date 
 
 
________________________ 
Title  
 
Sponsor Signature: 
All information concerning the study device supplied by Fundación Investigación HM Hospitales in 
connection with this study, and not previously published, is considered confidential and proprietary 
information. This information includes the clinical investigation plan, subject informed consent and 
case report forms. This confidential information shall remain the sole property of Fundación 
Investigación HM Hospitales, shall not be disclosed to others without prior written consent from 
Fundación Investigación HM Hospitales and shall not be used except in the performance of this study.  
The information developed during the conduct of this clinical study is also considered confidential and 
will be used by Fundación Investigación HM Hospitales in connection with the development of the 
study device. This information may be disclosed as deemed necessary by Fundación Investigación HM 
Hospitales. 
The below-named individuals are authorized to sign this clinical investigation plan and its 
amendments. 
 
________________________ 
 
 
_____ /_____ /_________ 
Signature 
 
 
 
 
 
Date 
 
 
________________________ 
 
 
________________________  
Printed Name 
 
Title 

 
 
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Epidural Pulsed Radiofrequency versus Epidural Steroids Injection for Treatment of 
Failed Back Syndrome: A Prospective, Randomized, Single-Blind and Multicenter Study 
CONFIDENTIAL 
1. - SUMMARY 
1. Study Title: 
Epidural Pulsed Radiofrequency versus Epidural Steroids Injection for Treatment of Failed 
Back Syndrome: A Prospective, Randomized, Single-Blind and Multicenter Study 
2. Sponsor: 
Fundación Investigación HM Hospitales 
3. Type of Clinical Investigation: 
Clinical Investigation with CE-marked medical devices. 
4. Coordinating Investigator: 
Dr. Agustín Mendiola de la Osa, MD PhD. 
5. Protocol Code: 
EPIPUL 
6. Geography 
Spain 
7. Clinical Sites: 
• Hospital Universitario Puerta de Hierro (Madrid, Spain). 
• Hospital Universitario Rey Juan Carlos (Madrid, Spain). 
• Hospital Universitario de Sanchinarro (Madrid, Spain) 
• Hospital Fremap Majadahonda (Madrid, Spain) 
• Hospital Universitario La Fé (Valencia, Spain) 
• Hospital Clínico Universitario de Santiago (Santiago de Compostela, Spain) 
8. Study Purpose: 
The present pilot study suggests that the epidural application of PRF to the dorsal roots 
and proximal DRG can be safe and effective in the treatment of intractable pain after back 
surgery. Several explanatory hypotheses motivate further study of this apparent 
improvement over transforaminal PRF, which has produced inconsistent results in 
published reports to date. 
9. Treatments 
Experimental Group (62 patients): Epidural radiofrequency by catheter in the epidural 
space plus steroids administration. 
Control Group (62 patients): Epidural steroids injection. 
10. Primary Endpoint: 
Difference in pain reduction between the control group and the experimental group since 
the baseline visit and the 6 month visit evaluated by Visual Analogue Scale (VAS). 
11. Secondary Endpoints: 
• Change from Baseline in pain at 1, 2 and 4 months (Visual Analogue 
Scale, VAS). 
• Change from Baseline in disability at 1, 2 and 6 months (assessed by Oswestry 
Disability Index, ODI).  
• Change from Baseline in health survey at 1, 2, 4 and 6 (assessed by Short Form 
Health Survey, SF-12). 
• Change from Baseline in neuropathic pain at 1, 2 and 6 months (assessed by Douleur 
Neuropathique 4 Questions, DN4). 
• Change from Baseline in improvement of pain at 1, 2, 4 and 6 months (assessed by 
Patient Impression of Improvement, PGI-I). 
• Assessment of subject satisfaction with experimental procedure 2 and 6 months. 
• Incidence of unanticipated adverse device effects. 
• Change in opioid intake in 6 months. 
• Adverse events related to procedures (experimental group and control group). 
12. Study Design: 
Prospective, randomized, single-blind and multi-centre study. 
Controlled comparison between epidural steroids injection with catheter and epidural 
radiofrequency by catheter in the epidural space plus steroids administration. 
After the treatment, patients will be followed-up at 1, 2, 4 and 6 months. 
 

 
 
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Epidural Pulsed Radiofrequency versus Epidural Steroids Injection for Treatment of 
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CONFIDENTIAL 
13. Eligibility Criteria: 
 
 
 
 
 
 
 
 
 
 
Inclusion Criteria:
1. Men and women over 18 years old. 
2. Written informed consent according to ICH/GCP and Spanish legislation, obtained 
before any study procedure. 
3. Pain VAS score at least 5 points. 
4. Duration of pain at least 3 months after back surgery with conservative treatment. 
5.  Leg-dominant radicular pain deemed neuropathic based on clinical history and 
examination. 
6. Responsive to selective radicular nerve block (bupivacaine 0.125%). 
7. Patients who have had a previous epidural steroid injection. 
Exclusion Criteria: 
1. Pregnancy or lactation. 
2. Inability to give informed consent in the absence of a legal representative. 
3. Subjects that are participating in a study with medicines or other clinical devices. 
4 Those who show inability to follow the instructions or collaborate during the 
development of the study. 
5. If in the opinion of the researcher there are findings in the physical examination, 
abnormalities in the results of the clinical analyses or other medical, social or psychosocial 
factors that could have a negative influence. 
6. Patients with myelopathy, systemic diseases, infection (systemic or local), cancer, 
indication for immediate surgery, coagulation disorders, use of anticoagulants, diabetes 
mellitus or multiple sclerosis. 
7. Life expectancy of less than one year. 
8. A current diagnosis of a progressive neurological disease. 
14. Study Population: 
Patients with chronic lumbar radicular pain following failed back surgery. 
15. Sample Size: 
62 patients per group, a total of 124 patients. 
16. Research Ethics Committee: 
CEIm HM Hospitales 
17. Calendar: 
The total duration of the study from first enrolment to last subject last visit is estimated to 
be 28 months: 
• 4 months to prepare all documentation for contracts and Committee approval. 
• 12 months for enrolment. 
• 6 months follow up. 
• 6 months to close the investigation and provide final study report. 
 
 
 

 
 
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CONFIDENTIAL 
2. – INDEX 
1. - SUMMARY ....................................................................................................................... 3 
2. – INDEX .............................................................................................................................. 5 
3. - GENERAL INFORMATION ................................................................................................. 7 
3.1 Clinical Investigation Identification ........................................................................ 7 
3.2 Type of Study .......................................................................................................... 7 
3.3 Description of the Device Study ............................................................................. 7 
3.4 Data Related to the Sponsor .................................................................................. 7 
3.5 Monitor Identification ............................................................................................ 7 
3.6 Information on the Investigator Team ................................................................... 7 
3.7 Expected Duration of the Clinical Investigation ..................................................... 7 
3.8 Data Safety Monitoring Board (DSMB) .................................................................. 8 
4. - JUSTIFICATION ................................................................................................................. 8 
5. - HYPOTHESIS AND ENDPOINTS ...................................................................................... 10 
5.1 Hypothesis ............................................................................................................ 10 
5.2 Primary Endpoint ................................................................................................. 11 
5.3 Secondary Endpoints ............................................................................................ 11 
6. - ELIGIBILITY CRITERIA ..................................................................................................... 12 
6.1 Inclusion Criteria .................................................................................................. 12 
6.2 Exclusion Criteria .................................................................................................. 12 
7. - STUDY DESIGN ............................................................................................................... 12 
7.1 Type of Clinical Investigation ............................................................................... 12 
7.2 Randomization Process ........................................................................................ 12 
7.3 Sample Size and justification ................................................................................ 13 
7.4 Blinding................................................................................................................. 13 
7.5 Study Plan ............................................................................................................. 13 
7.6 Evaluation Endpoints ............................................................................................ 16 
7.7 Early Subject Withdrawal ..................................................................................... 17 
7.8 Study Completion ................................................................................................. 17 
7.9 Study Suspension and Termination ...................................................................... 17 
7.10 Definition of Population for Analyses ................................................................ 18 
8. – SAFETY ASPECTS ........................................................................................................... 19 
8.1 Adverse Events ..................................................................................................... 19 
8.2 Adverse Device Effect (ADE) ................................................................................. 20 
8.3 Unanticipated serious adverse device effect (USADE) ......................................... 21 
8.4 Anticipated serious adverse device effect (ASADE) ............................................. 21 
8.5 Device Deficiency ................................................................................................. 21 
8.6 Serious adverse device effect ............................................................................... 21 

 
 
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CONFIDENTIAL 
8.7 Severity ................................................................................................................. 21 
8.8 Reporting. ............................................................................................................. 22 
Table1. Schedule ........................................................................................................ 23 
9. - TREATMENT DESCRIPTION ............................................................................................ 24 
9.1 Control Group. Epidural Steroids Injection. ......................................................... 24 
9.2 Experimental Group. Epidural Pulsed Radiofrequency. ....................................... 25 
10. - PRACTICAL CONSIDERATIONS AND ETHICALS ASPECTS ............................................. 26 
10.1 General Considerations ...................................................................................... 26 
10.2 Informed Consent .............................................................................................. 26 
10.3 About the Participating Staff .............................................................................. 26 
10.4 Security Devices and Confidentiality .................................................................. 27 
11. - ECONOMICAL ASPECTS ............................................................................................... 28 
11.1 Insurance Policy ................................................................................................. 28 
12. - PUBLICATIONS RIGHTS ................................................................................................ 28 
13. - STATISTIC ANALYSIS ..................................................................................................... 28 
14. - BIBLIOGRAPHY ............................................................................................................. 29 
15. - ANEXES ........................................................................................................................ 35 
15.1 Annex I. Information on the Investigator Team ................................................. 35 
15.2 Annex II. Study Forms ......................................................................................... 36 
 
 
 

 
 
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CONFIDENTIAL 
3. - GENERAL INFORMATION 
3.1 Clinical Investigation Identification 
Protocol Code: EPIPUL 
Title of the Clinical Investigation: Epidural Pulsed Radiofrequency versus Epidural 
Steroids Injection for Treatment of Failed Back Syndrome: A Prospective, 
Randomized, Single-Blind and Multicenter Study. 
3.2 Type of Study  
Clinical trial with a CE marked Medical Device used within its intended purpose 
and according to its authorized indications.  
3.3 Description of the Device Study 
3.3.1. RCE Introducer Cannulae (RCE-C916S-P). 
3.3.2. RCE 40 cm Electrodes (RCE-E401519-P). 
3.3.3. G4 RF Generator (RFG-4-120 V). 
3.3.4. Disposable Ground Pads (DGP-PM-10). 
3.3.5. Voltage Controlled Injection Electrode. Length 10 cm / Tip 5 mm / Echo RF 
(CR-10-P). 
3.4 Data Related to the Sponsor 
Fundación Investigación HM Hospitales, 
Hospital Universitario HM Sanchinarro 
Calle Oña 10 
28050 Madrid (Spain) 
E-mail:    
3.5 Monitor Identification 
Monitor to be assigned by the Sponsor. 
3.6 Information on the Investigator Team  
See Annex I. 
3.7 Expected Duration of the Clinical Investigation 
The overall duration of the study will be twenty-eight months, one year of 
recruitment and six months of follow-up, from the inclusion of the first patient until 
the last follow-up visit of the last patient.  

 
 
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CONFIDENTIAL 
3.8 Data Safety Monitoring Board (DSMB) 
A Data Safety Monitoring Board (DSMB), independent from the EPIPUL 
consortium, will be appointed to perform an independent supervision of the safety 
aspects of the study. The DSMB will have 3 members including at least one expert in 
clinical trial methodology and statistics, and one pain management expert 
independent from the study team. The DSMB will be established before the start of 
the study and will follow the procedures established in the “DSMB Charter for the 
EPIPUL study”.  
4. - JUSTIFICATION 
Over the last twenty years, Pulsed Radiofrequency (PRF) has been applied to 
nerves as a less destructive alternative to thermal RF ablation (RFA) for pain 
reduction without disruption of somatic sensation and motor function 1. PRF delivers 
RF in bursts that expose a target nerve to high-intensity electric fields (E-fields) but 
avoids gross thermal ablation by allowing electrically-generated heat to dissipate 
between bursts. Though the mechanism of PRF has not yet been fully established, 
theoretical and experimental findings suggest that the RF electric-field induces 
moderately disruptive 2, 3, 4, 5, 6, 7, 8 and neuromodulatory effects in primary sensory 
neurons and dorsal horn 2, 3, 7, 9, 10, 11, 12, 13, 14, 15, 16 that can reduce neuropathic 
hyperalgesia/allodynia 14, 15, 16, 17, 18, 19, 20, 21, 22. Clinically, PRF is often applied using a 
“transforaminal” approach whereby a sharp RF cannula/electrode is positioned near 
a DRG and/or spinal nerve via the neural foramina. Transforaminal PRF of the DRG 
has been used for treatment of cervical radicular pain 23, 24, 25, lumbar radicular pain 
24, 26, 27, 28, 29, postsurgical thoracic pain 26, 30, stump pain 31, postsurgical ilioinguinal 
neuralgia 32, and other pain disorders. PRF has also applied to the suprascapular 
nerve for shoulder pain 33, 34, 35, the saphenous 36 or sciatic nerves 37 for knee pain, 
the obturator and femoral nerves for hip pain 38, the genitofemoral or ilioinguinal or 
iliohypogastric nerve for groin pain or orchialgia 39, the lateral femoral cutaneous 
nerve for meralgia paresthetica 40, the intercostal nerve for postherpetic neuralgia 41, 
the Gasserian ganglion for trigeminal neuralgia 42, the greater and lesser occipital 
nerves for occipital neuralgia 43, 44, a stump neuroma for phantom limb pain 45, and 
other peripheral targets.  
Failed Back Surgery Syndrome (FBSS) refers to a diverse array of chronic back or 
leg pain disorders that are either caused or untreated by a previous back surgery 46, 
47, 48. FBSS can involve multiple nociceptive and neuropathic pain etiologies for each 
patient, including internal disc disruption, facet and sacroiliac joint syndromes, 
structural instability, spondylitis, radiculitis, disc herniation, neural or spinal foramina 
stenosis, arachnoiditis, epidural and other postsurgical fibrosis, and other disorders. 
Whether due to FBSS inherent heterogeneity, multisegmental involvement or lack of 
specific diagnostic criteria, FBSS pain can be challenging to treat. Epidural steroids 
injection is currently the most common treatment for FBSS while transforaminal PRF 

 
 
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CONFIDENTIAL 
of the DRG and epidurolysis has produced mixed results 26, 27. The present study 
explores the hypothesis that treatment of FBSS pain can be improved by epidural 
application of PRF to the DRG and dorsal nerve root, thereby reducing or blocking 
ectopic pain signals originating from sites of dorsal root irritation within the spine 49, 
50, 51, in addition to ectopia from the DRG 49, 52, 53, 54, 55 and nociceptive signals from 
other painful anatomy. This study also explores the concept that epidural access can 
facilitate treatment of all affected dorsal roots and DRGs, some of which may be 
inaccessible transforaminal due to implanted hardware and bone anatomy.  
Insausti et al. previously presented case reports about Epidural Radiofrequency 
with Catheter (ERC), wherein pulsed RF was delivered to lumbosacral nerve roots 
using an epidurolysis catheter inserted through the sacral hiatus without 
temperature control 56. More recent case reports describe a similar technique using 
a catheter electrode that is specifically designed and indicated for radiofrequency 
treatment, and that includes a temperature sensor, an elongated 15-mm active tip, a 
generator connection, and an injection port (RCE-E401519-P, Cosman Medical, Inc., 
Burlington, MA, USA) 57,58. Temperature monitoring was used to limit the risk of 
exposing spinal nervous tissue to neurolytic temperatures, and to maximize the 
electric-field dose (E-dose) under the 42 °C safety limit 3, 13, 59. A longer active tip was 
used to increase the theoretical likelihood of placing the electrode active tip nearby 
the target nerve, and thus, of exposing that nerve to sufficiently strong E-fields. 
The epidural orientation of the affected nerve roots may be particularly useful for 
PRF treatment of any pain syndrome involving direct irritation of DRG, including 
FBSS. Mechanical, chemical or ischemic nerve injury can cause ectopic firing that 
originates from both the site of injury and the DRG 51, 63. While PRF is theorized to 
induce pain-relieving changes in the DRG and dorsal horn, structural and functional 
experiments also suggest that PRF may relieve pain at least in part using blockage of 
action potential propagation along smaller-diameter axons 4, 7. Consistent with this, 
PRF is generally applied between the spinal cord and the site of a nerve injury when 
used to treat neuropathic pain caused by peripheral nerve damage. It can be 
reasonably hypothesized that treatment of pain involving nerve dysfunction within 
the spine would be improved by PRF application to the epidural nerves in epidural 
space before DRG is formed, so that pain signals generated in the central axon 
(dorsal root), soma (DRG), and peripheral axon (peripheral nerve) of afferent 
neurons are all blocked from entering the central nervous system.  
Even if neuropathic pain is initiated only at a peripheral location, the application 
of PRF closer to the DRG has been associated with better outcomes 30, perhaps due 
to cessation or blockage of painful ectopic discharge emanating from the DRG in 
neuropathy 63. Provided that the spinal canal is not itself restricted, epidural 
electrode placement can improve the positioning of the electrode active tip near the 
DRG, particularly at spinal levels that are inaccessible transforaminal due to 
implanted hardware, osteophytes overgrowth, or normal vertebral anatomy. Dorsal 

 
 
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Epidural Pulsed Radiofrequency versus Epidural Steroids Injection for Treatment of 
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CONFIDENTIAL 
roots and epidural nerves are organized somatotopically within the spinal canal 64, 
and each DRG is located at a regular position relative to the pedicle 65 which can be 
readily visualized radiographically relative to a radiopaque catheter electrode.  
The PRF electric field strength decreases with distance from the electrode and 
across the width of a target nerve, so the relative position of a PRF electrode and 
target nerve likely affects efficacy 3. Epidural placement may enhance nerve 
targeting and exposure to E-fields by tending to orient of the side of the electrode 
active tip across the nerve 3, 65, by allowing for use of a longer active tip (eg 15 mm 
epidurally vs. 5-10 mm transforaminal), and by avoiding physician hesitance to insert 
a sharp cannula deep into the neural foramina or near critical blood vessels 30. The 
epidural approach also facilitates the treatment of pain disorders with 
multisegmental and bilateral involvement, by providing for targets of multiple spinal 
nerves through a single needle insertion. In contrast, the transforaminal approach 
requires a separate needle to be placed at each spinal level and side.  
Differences in patient selection and methods from the previous study of 
transforaminal PRF 27 could also account for the apparent superiority of epidural 
over transforaminal PRF for the treatment of FBSS pain. In a previous study, PRF 
applied at each DRG for 120 seconds was unsuccessful in consistently reducing FBSS 
pain 27. In the present study, PRF was applied at each level for 480 seconds. This 
longer treatment time likely increased the duration for which target nerves were 
exposed to the PRF electric field and could explain improved outcomes.  
Temperature control is important for safe and effective application of PRF in the 
epidural space. Though no complications were reported during voltage-controlled 
epidural PRF 56, inadvertent exposure of nervous structures within the spinal canal to 
neurolytic temperatures could produce substantial complications. Temperature 
control also enables the delivery of the maximal pulsed RF electric field intensity and 
duration under the safety temperature limit of 42 °C 59, which was associated with 
greater pain reduction in a rat neuropathic pain model than was PRF delivery at 37 
°C 13. In the absence of temperature control, PRF efficacy may be limited by the need 
to preemptively moderate PRF parameters so that neurolytic temperatures are 
avoided under a wide variety of tissue conditions, electrode sizes, and patients 59. 
These factors can vary greatly, as evidenced by our comparison of impedance and 
current measurements from small transforaminal electrodes and larger epidural 
electrodes. 
5. - HYPOTHESIS AND ENDPOINTS 
5.1 Hypothesis 
This clinical investigation will intends to demonstrate reduction of chronic lumbar 
radicular pain following back surgery by epidural application of temperature-

 
 
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Epidural Pulsed Radiofrequency versus Epidural Steroids Injection for Treatment of 
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controlled PRF to the dorsal radicular filaments proximal to the DRG and dorsal nerve 
root in the epidural space using a guidable, radio-opaque, catheter electrode (Boston 
Scientific RCE) having an elongated 15-mm active tip and a temperature sensor at its 
rounded distal point (Cosman RCE-E401519-P) versus epidural steroids injection. 
5.2 Primary Endpoint 
Difference in pain reduction between the control group and the experimental 
group since the baseline visit and the 6 month visit evaluated by Visual Analogue 
Scale (VAS). 
5.3 Secondary Endpoints 
5.3.1. Change from Baseline in pain at 1, 2 and 4 months (assessed by Visual 
Analogue Scale, VAS). 
5.3.2. Change from Baseline in disability at 1, 2 and 6 months (assessed by 
Oswestry Disability Index, ODI). 
5.3.3. Change from Baseline in health survey at 1, 2, 4 and 6 months (assessed by 
Short Form Health Survey, SF-12). 
5.3.4. Change from Baseline in neuropathic pain at 1, 2 and 6 months (assessed by 
Douleur Neuropathique 4 Questions, DN4). 
5.3.5. Assessment of improvement of pain with experimental procedure at 1, 2, 4 
and 6 months (assessed by Patient Impression of Improvement, PGI-I). 
5.3.6. Incidence of unanticipated adverse device effects. 
5.3.7. Change in opioid intake in 6 months. 
5.3.8. Adverse events related to procedures (experimental group and control 
group). 
5.3.9. Assessment of subject satisfaction with experimental procedure at 2 and 6 
months. 

 
 
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6. - ELIGIBILITY CRITERIA 
6.1 Inclusion Criteria 
1. Men and women over 18 years old. 
2. Written informed consent according to ICH/GCP and Spanish legislation, 
obtained before any study procedure. 
3. Pain VAS score at least 5 points. 
4. Duration of pain at least 3 months after back surgery with conservative 
treatment. 
5.  Leg-dominant radicular pain deemed neuropathic based on clinical history and 
examination. 
6. Responsive to selective radicular nerve block (bupivacaine 0.125%). 
7. Patients who have had a previous epidural steroid injection. 
6.2 Exclusion Criteria 
1. Pregnancy or lactation. 
2. Inability to give informed consent in the absence of a legal representative. 
3. Subjects that are participating in a study with medicines or other clinical devices. 
4 Those who show inability to follow the instructions or collaborate during the 
development of the study. 
5. If in the opinion of the researcher there are findings in the physical examination, 
abnormalities in the results of the clinical analyzes or other medical, social or 
psychosocial factors that could have a negative influence.  
6. Patients with myelopathy, systemic diseases, infection (systemic or local), cancer, 
indication for immediate surgery, coagulation disorders, use of anticoagulants, 
diabetes mellitus or multiple sclerosis. 
7. Life expectancy of less than one year. 
8. A current diagnosis of a progressive neurological disease. 
7. - STUDY DESIGN 
7.1 Type of Clinical Investigation 
Prospective, randomized, single-blind and multi-center study. 
Controlled comparison between epidural and transforaminal electrode placement 
and epidural steroids injection. 
7.2 Randomization Process 
The clinical investigation will be single-blind. The assignment to the type of 
surgical treatment is carried out randomly and open for the investigators but not for 

 
 
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the patients. Randomization will be done with concealment of the randomization 
sequence and it takes place after informed consent has been signed. 
7.3 Sample Size and justification 
Pain reduction at least thirty millimeters between the baseline visit and the 6 
months visit in patients assigned to the experimental group evaluated by the Visual 
Analogue Scale (VAS). Pain reduction of twenty millimeters less in the experimental 
group than in the control group since the baseline visit and the 6 months visit 
evaluated by the Visual Analogue Scale (VAS).  
To achieve a power of 90.00% to detect differences in the contrast of the null 
hypothesis H₀: μ₁ = μ₂ through a bilateral T-Student Test for two independent 
samples, taking into account that the level of significance is 5%, and assuming that 
the mean of the difference in VAS of the 6-month radiofrequency plus steroid group 
is 40 mm, the average of the control group is 60 mm and the standard deviation of 
both groups is 30 mm, with an estimate of losses of the 20%, it will be necessary to 
include 62 patients per group, total of 124 patients. 
7.4 Blinding 
This study is single-blind. 
7.5 Study Plan 
7.5.1. Screening 
At this clinic visit the subject will undergo the following evaluations:  
• Sing Informed Consent. 
• Demographics will be collected. 
• A medical, pain and surgical history will be collected. 
• Subjects will be asked to fill out VAS questionnaire. 
• Medication use will be collected. 
• Eligibility criteria will be evaluated. 
All applicable information will be documented on a CRF. 
7.5.2. Baseline* (within 30 days from Screening Visit) 
At this clinic visit the subject will undergo the following evaluations:  
• Randomization. 
• Eligibility criteria will be re-evaluated. 
• Any change of medication will be collected. 

 
 
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• Subjects will be asked to fill out standard questionnaires to assess (VAS, ODI, 
SF-12 and DN4). 
• Subjects will be assessed for possible adverse events, if any. 
• AP and lateral view lumbar imaging. 
• Screening failures will be collected. 
*Baseline and Treatment visits could be at the same time. 
All applicable information will be documented on a CRF. 
7.5.3. Treatment Visit (± 15 days) 
At this clinic visit the subject will undergo the following evaluations:  
• Treatment process. 
• Study completion (if applicable). 
• Adverse event monitoring. 
• Deviation monitoring. 
• Any change of medication will be collected. 
7.5.4. 1 Month Visit (± 7 days) 
At this clinic visit the subject will undergo the following evaluations:  
• Any change of medication will be collected. 
• Subjects will be asked to fill out standard questionnaires to assess (VAS, ODI, 
SF-12, DN4 and PGI-I). 
• Subjects will be assessed for possible adverse events, if any. 
• Adverse event monitoring. 
• Deviation monitoring. 
All applicable information will be documented on a CRF. 
 
7.5.5. 2 Months Visit (± 14 days) 
At this clinic visit the subject will undergo the following evaluations: 
• Any change of medication will be collected. 
• Subjects will be asked to fill out standard questionnaires to assess (VAS, ODI, 
SF-12, DN4 and PGI-I). 
• Subjects will be assessed for possible adverse events, if any. 
• Adverse event monitoring. 
• Deviation monitoring. 
• Subject questionnaire of treatment satisfaction. 

 
 
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All applicable information will be documented on a CRF. 
 
7.5.6. 4 Months Visit (± 14 days) 
At this clinic visit the subject will undergo the following evaluations: 
• Any change of medication will be collected. 
• Subjects will be asked to fill out standard questionnaires to assess (VAS, SF-
12 and PGI-I). 
• Subjects will be assessed for possible adverse events, if any. 
• Adverse event monitoring. 
• Deviation monitoring. 
All applicable information will be documented on a CRF. 
 
7.5.7. 6 Months Visit (± 20 days) 
At this clinic visit the subject will undergo the following evaluations: 
• Any change of medication will be collected. 
• Subjects will be asked to fill out standard questionnaires to assess (VAS, ODI, 
SF-12, DN4 and PGI-I). 
• Subjects will be assessed for possible adverse events, if any. 
• Adverse event monitoring. 
• Deviation monitoring. 
• Subject questionnaire of treatment satisfaction. 
All applicable information will be documented on a CRF. 
 
7.5.8. Unscheduled Visit 
At this clinic visit the subject will undergo the following evaluations: 
• Any change of medication will be collected. 
• Subjects will be asked to fill out standard questionnaires to assess (VAS, ODI, 
SF-12, DN4 and PGI-I). 
• Subjects will be assessed for possible adverse events, if any. 
• Study completion (if applicable). 
• Adverse event monitoring. 
• Deviation monitoring. 
• Subject questionnaire of treatment satisfaction. 
All applicable information will be documented on a CRF. 

 
 
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7.6 Evaluation Endpoints 
 Primary endpoint 
 Visual Analogue Scale (VAS): The VAS measures the pain intensity reported by 
the subject. Subject scores the intensity of pain on a 10 mm line. The VAS in this 
study consists of a 10 mm line with one indicating “No Pain” and the other end 
indicating “Worst imaginable pain”. Upon completion by the subject VAS scores 
will be measured and converted to a numeric value (0.0 mm to 10.0 mm) by site 
staff personnel. VAS is the most widely used outcome measure in assessing pain 
due to its documented reliability and validity, ease in administration, and minimal 
training requirements for the administrator.  
 
Subjects will complete a mean VAS score for leg and back pain: at Baseline, 
months 1, 2, 4, 6 and if applicable at the Unscheduled visit. The change in leg and 
back pain VAS scores, the percentage change in leg and back pain VAS scores, and 
the responder rate for leg and back pain will be calculated and summarized for 
each visit. 
 
 Secondary Endpoints. 
- Oswestry Disability Index (ODI): The ODI measures functional disability as 
reported by the subject. Subjects will complete ODI during the study visits: at 
Baseline, months 1, 2, 6 and if applicable at the Unscheduled visit. The changes in 
functional disability will be summarized as continuous variables.  
- Short Form Health Survey (SF-12): The SF-12 measure health status reported 
by subject at: Baseline, months 1, 2, 4, 6 and if applicable at the Unscheduled visit. 
The changes in health status will be summarized as continuous variables. 
- Douleur Neuropathique 4 Questions (DN4): The DN4 measures the 
neuropathic pain reported by the subject. Subjects will complete DN4 during the 
study visits: at Baseline, months 1, 2, 6 and if applicable at the Unscheduled visit. 
The changes in neuropathic pain will be summarized as continuous variables. 
- Patient Impression of Improvement questionnaire (PGI-I): The PGI-I measure 
subjective improvement in pain. Subjects will complete PGI-I form during the study 
visits at: month 1, 2, 4, 6 and if applicable at the Unscheduled visit. 
- Medication Usage: morphine equivalent units of opioid medications; other 
non-opioid pain medications. Assessed at: Baseline, months 1, 2, 4, 6 and if 
applicable at the Unscheduled visit. 
- 5-point scale where 1 is “very satisfied” to 5 that is “very dissatisfied”; their 
charging convenience and remote control use during the study visits: Months 2, 6 
and if applicable at the Unscheduled visit. The responses will be summarized. Study 
personnel will be appropriately trained for administration of each test. 

 
 
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- Safety (device and procedures): Safety will be assessed by characterizing 
clinically meaningful change in adverse events at all study visits and in related to 
medical device or procedures. 
7.7 Early Subject Withdrawal 
Subjects may be withdrawn early from the study for a number of reasons, 
including but not limited to: 
• Subject request. 
• Investigator request. 
• Subject lost to follow up. 
• Subject death. 
• Intolerable adverse events. 
If a subject is discontinued from the study early, a Termination CRF will be 
completed describing the reason for discontinuation. The Investigator should make 
all attempts to conduct a visit within 10 days (±4 days) after withdrawal from the 
study. If a subject has withdrawn consent for the study, or is lost to follow-up, the 
completion of this visit is not imperative. In situations where study withdrawal is due 
to an adverse event, subjects will be followed until resolution of that adverse event 
or determination that the subject’s condition is stable. 
In case of an Early Subject Withdrawal the subject will be assessed for adverse 
events, if any, and medication use. This will be documented on an Unscheduled Visit 
CRF. 
In case the Early Subject Withdrawal happened at a study specific follow-up visit 
(see Table 1. Schedule of Events) no Unscheduled Visit CRF need to be completed. 
7.8 Study Completion 
All subjects enrolled in this study are expected to complete all scheduled visits 
through the 6 Months Follow-Up Visits. A Study Completion CRF should be 
completed at this visit. In situations where there is an ongoing device related adverse 
event, subjects will be followed until resolution of that adverse event or 
determination that the subject’s condition is stable, at which point the Study 
Completion CRF should be completed. 
7.9 Study Suspension and Termination 
The study may be terminated when all of the requirements of the investigational 
plan have been fulfilled. Subjects will be considered to have completed all study 
requirements following completion of the 6 Months Follw-Up Visits. The clinical sites 
will be considered to have completed the study requirements at the end of the 
clinical site close out monitoring visit. The study will be considered terminated when 

 
 
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all close out visits have been completed and all Sponsor and Investigator reports 
have been issued.  
Sponsor, the Investigators, or the EC may suspend or terminate the study early at 
any time. If the study is suspended or terminated prematurely, all currently enrolled 
subjects will be withdrawn from the study and a Study Completion/Termination CRF 
will be completed. If there is an ongoing event related to the device or therapy, the 
subject will be followed until resolution of that adverse event or determination that 
the subject’s condition is stable. 
The Sponsor reserves the right to terminate the study, but intends only to 
exercise this right for valid scientific or business reasons, or reasons related to the 
protections of the study subjects. Investigators and ECs will be notified in writing in 
the event of study termination. Possible reasons for study termination include, but 
are not limited to the discovery of unexpected, significant, or unacceptable risk to 
subjects enrolled in the study. 
The Sponsor reserves the right to stop the enrollment of subjects at a clinical site 
at any time after the clinical site initiation visit if no subjects have been enrolled, or if 
the clinical site has multiple deviations from the clinical investigational plan without 
justification, or fails to follow remedial actions. Possible reasons for suspending or 
terminating a clinical site may include, but are not limited to:  
• Investigator non-compliance. 
• Repeated failure to complete or submit CRFs in a timely manner. 
• Failure to obtain written informed consent. 
• Failure to report SAEs or USADEs to the Sponsor and/or EC within 24 
hours of knowledge. 
• Failure to control or account for investigational products used. 
7.10 Definition of Population for Analyses 
We define 3 different subject populations for analysis:  
1. Intent-to-Treat (ITT)  
• All subjects who receive any treatment of the groups (Experimental or Control)  
2. Per Protocol (PP) 
• All subjects who receive treatment of the study and complete the Primary 
Effectiveness Assessment (Primary Endpoint defined above).  
3. ITT-Baseline (ITT-B)  

 
 
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• All subjects who complete baseline assessment. In order to capture AEs that 
occur prior to the 6 months follow-up visit. 
8. – SAFETY ASPECTS  
The definitions presented in this section allow for a clear understanding of adverse 
event data collection and reporting requirements. 
 
Medical Device  
Any instrument, apparatus, implement, machine, appliance, implant, software, 
material or other similar or related article. 
Intended by the manufacturer to be used, alone or in combination, for human 
beings for one or more of the specific purpose (s) of: 
 Diagnosis, prevention, monitoring, treatments or alleviation of disease,  
 Diagnosis, monitoring, treatment, alleviation of, or compensation for, an injury,  
 Investigation, replacement, modification, or support of the anatomy or of a 
physiological process,  
 Supporting or sustaining life,  
 Control of conception,  
 Disinfection of medical devices and 
 Which does not achieve its primary intended action in or on the human body by 
pharmacological, immunological or metabolic means, but which may be assisted in its 
intended function by such means. The term ‘medical device’ is usually defined by 
national regulations.  
8.1 Adverse Events  
The following adverse events will be recorded in the eCRF of the study:  
- All serious adverse events.  
- All adverse events considered of interest for this study, regardless of their 
seriousness. 
NOTE - As the primary efficacy measure in this study is pain, leg and back pain does not 
need to be reported as an adverse event unless it meets the definition of a serious 
adverse event. However, Investigators may, at their discretion, report any pain-related 
adverse events during the study. 
 
 

 
 
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8.1.1 Serious Adverse Event (SAE) 
An adverse event (AE) includes any unforeseen illness or injury or adverse 
clinical sign (including abnormal laboratory results) related or not to the 
investigational product. This includes events related to the product or to the 
comparator, or to the procedures involved.  
It will be considered a serious adverse event (SAE) when:  
 Causes death.  
 It leads to a significant deterioration in the patient's health that results 
in:  
- Illness or injury that threatens life. 
- A permanent deterioration of a body structure or function. 
- Hospitalization or prolongation of hospitalization. 
- Medical or surgical intervention to prevent a life-threatening illness, 
injury or permanent disability of a body structure or function. 
 Led to fetal distress, fetal death, or a congenital abnormality or birth 
defect. 
Adverse events of interest for this study will be considered:  
- Duration of the procedures greater than 1 hour. 
- Problems related to the surgical wound. 
- Infection. 
NOTES: 
 Planned hospitalization for a pre-existing condition, or a procedure 
required by the CIP, without serious deterioration in health, is not 
considered a serious adverse event.  
 A pregnancy is not considered to be a serious adverse event but will be 
captured in the CRF as a non-serious adverse event to allow follow-up on 
the outcome of the pregnancy  
 Examples for serious deterioration are: cardiac arrest (CPR required), CVA, 
paralysis, sepsis, amputation, internal/external bleeding, cancer, fracture 
requiring intervention, myocardial infarction.  
8.2 Adverse Device Effect (ADE) 
An adverse event related to the use of a medical device.  
This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any 
malfunction of the medical device.  

 
 
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This definition includes any event resulting from the use error or from 
intentional misuse of the medical device.  
During this clinical investigation an event should be considered related to the 
device when it is the result of: 
 
The device components (e.g. lead, extension, Trial Simulator, Remote). 
 
The Therapy/simulation. 
8.3 Unanticipated serious adverse device effect (USADE)  
An unanticipated serious adverse device effect (USADE) is a serious adverse 
device effect that was not previously identified in nature, severity, or degree of 
incidence in the investigational plan or application (including a supplementary plan 
or application), or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects.  
Those known adverse events related to the device, procedure or therapy is 
listed in the Risk Analysis section.  
8.4 Anticipated serious adverse device effect (ASADE)  
A serious adverse device effect which by its nature, incidence, severity or 
outcome has been previously identified in the risk analysis report.  
Untoward medical occurrences that are not unanticipated, i.e. are unsurprising, 
are identified in the Physician Manual or CIP and ICF. 
8.5 Device Deficiency  
PRF is a CE marked (as well as TGA and FDA approved) device which meets 
vigilance reporting criteria. Device Deficiencies will be handled under the post-
market surveillance / vigilance system from the Sponsor.  
8.6 Serious adverse device effect  
Adverse device effect that has resulted in any of the consequences characteristic 
of a serious adverse event.  
8.7 Severity  
The Investigator will use the following definitions to rate the severity of each 
adverse event:  
• Mild: Awareness of a sign or symptom that does not interfere with the 
subject’s usual activity or is transient, resolved without treatment and no 
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• Moderate: Interferes with the subject’s usual activity or requires symptomatic 
treatment. 
• Severe: Symptom(s) causing severe discomfort with significant impact of the 
subject’s usual activity and requires treatment. 
8.8 Reporting.  
According to current regulations, professionals must report those incidents that 
are associated with a medical device or with the information provided with the 
product and that incident is such that is has caused death or a serious deterioration 
in health, or if it occurs again it can cause them. 
An incident is understood to be any malfunction, failure ore deterioration of the 
characteristics or operation of a product, as well as any deficiency in the labelling or 
in the instructions for use that could or have led to death or serious deterioration 
of the condition health of a patient or a user. The types of adverse incidents that 
must be reported are the following: 
1. Those that lead to death. 
2. Those that give rise to a serious deterioration of the state of health of the 
patient, user or other person, such as:  
• Illness or injury with threat to life.  
• Permanent deterioration of a bodily function or permanent damage to a 
body structure.  
• Process that requires medical or surgical intervention to avoid permanent 
deterioration of a bodily function or permanent damage to a body 
structure.  
 
3. Potential incidents, which are those that could have led to death or a serious 
deterioration of health, but that have not occurred due to fortunate circumstances 
or the intervention of health personnel.  
These incidents must be reported by the investigators. They must notify the 
sponsor of any serious incidents that may be related to the devices involved in the 
development of the investigation, through Annex III available at:  
https://www.aemps.gob.es/vigilancia/productosSanitarios/vig-prof-nota.htm#II  
And the sponsor must evaluate them and notify them to the surveillance points of 
medical devices of the CCAA, in accordance with the general guidelines established 
by the Medical Device Surveillance System for the notification of adverse incidents:  
https://www.aemps.gob.es/surveillance/healthproducts/professional-
monitoring.htm  
The Sponsor contact information for these events is: 
Dr. Agustín Mendiola de la Osa, 
E-mail: epipulpdh@gmail.com 

 
 
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Table1. Schedule 
 
Assessment 
Visit 
Screening 
Baseline 
Treatment 
1 month 
2 months 
4 months 
6 months 
Unscheduled 
Window 
Within 30 days from 
screening
± 15 days 
± 7 days 
± 14 days 
± 14 days 
± 20 days 
 
Pregnancy Test 
x 
Sign Informed Consent 
x 
Entry Criteria Evaluation 
x 
x 
Demographics 
x 
Medical History 
x 
x 
Randomization 
x 
Treatment Process 
x 
Pain and Surgical History 
x 
Medication Usage 
x 
x 
x 
x 
x 
x 
x 
VAS questionnaire 
x 
x 
x 
x 
x 
x 
ODI questionnaire 
x 
x 
x 
x 
x 
SF-12 questionnaire 
x 
x 
x 
x 
x 
x 
DN4 questionnaire 
x 
x 
x 
x 
x 
PGI-I questionnaire 
x 
x 
x 
x 
x 
Subject questionnaire of treatment satisfaction 
x 
x 
x 
AP and Lateral radiography imaging 
x 
Deviation Monitoring 
x 
x 
x 
x 
x 
x 
Adverse Event Monitoring 
x 
x 
x 
x 
x 
x 
x 
Screening Failures 
x 
Study Completion 
x 
x 
x 

 
 
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9. - TREATMENT DESCRIPTION 
Both treatments (control group and experimental group) will always be 
performed in an ambulatory environment through sedation and anaesthesia.  
The lower back and buttocks will be prepared for an aseptic technique. Lateral 
and AP views of the sacral foramina and hiatus will be taken and the entry point for 
the epidural needle will be marked on the surface of the skin, 1-2 cm caudal to the 
sacral hiatus. The skin and subcutaneous tissue underlying the entry site will be 
anesthetized using 1-2 ml of 1% lidocaine. 
A 9-cm-long, 16-gauge (ga) epidural needle (Cosman RCE-C916S-P) is inserted 
through the skin and into the caudal canal, 1-2 cm beyond the sacral hiatus, ending 
at an angle of approximately 15º concerning the skin. Intravascular and subdural 
placement will be ruled out by injecting 1-1.5 ml of non-ionic radiographic contrast 
(180 mg of iohexol per ml) through the fluoroscopic needle in vivo. 
9.1 Control Group. Epidural Steroids Injection. 
A radiopaque, guidable radiofrequency electrode (Cosman RCE-E401519-P) will 
bend slightly at a 45º angle proximal to its metal tip and then be inserted through 
the needle. The electrode shall include an active 20/15 mm gauge tip, a 19/40 cm 
gauge shaft, a rounded distal point temperature sensor, an injection port and an 
integral generator connection. The electrode will be visualized by fluoroscopy as it is 
guided in the epidural space from the sacral canal to the lumbar vertebral canal.  
The electrode will be connected to an output of the RF generator (Cosman RFG-4-
120V/GF RF Generator). To provide a monopolar PRF operation, a ground pad 
(Cosman DGP-PM-10) will be placed on a shaved muscle part of the posterolateral 
thigh skin and connected to the reference socket of the RF generator with voltage 0 
for 240 seconds (to ensure single-blind).  
Intravascular and subdural placement will be ruled out by injecting 1-1.5 ml of 
non-ionic radiographic contrast (180 mg of iohexol per ml) through the integral 
injection port of the electrode under live fluoroscopy. Subsequently, betamethasone 
12 mg will be administered. 
After treatment, the needle and electrode will be removed. A sterile dressing will 
be applied over the needle insertion site. The patient will be monitored (visualized by 
fluoroscopy) while the sedation is removed, the motor dysfunction of the leg is 
verified and then the patient will be discharged. 

 
 
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9.2 Experimental Group. Epidural Pulsed Radiofrequency. 
A radiopaque, guidable radiofrequency electrode (Cosman RCE-E401519-P) will 
bend slightly at a 45º angle proximal to its metal tip and then be inserted through 
the needle. The electrode shall include an active 20/15 mm gauge tip, a 19/40 cm 
gauge shaft, a rounded distal point temperature sensor, an injection port and an 
integral generator connection. The electrode will be visualized by fluoroscopy as it is 
guided in the epidural space from the sacral canal to the lumbar vertebral canal. The 
electrode will be connected to an output of the RF generator (Cosman RFG-4-
120V/GF RF Generator). To provide a monopolar PRF operation, a ground pad 
(Cosman DGP-PM-10) will be placed on a shaved muscle part of the posterolateral 
thigh skin and connected to the reference socket of the RF generator. 
The active tip of 15 mm of the electrode will be placed in the internal aspect of 
the pedicle in each of levels L4, L5 and / or S1, on the right or left side, according to 
the patient's pain distribution (Figure 1). Intravascular and subdural placement will 
be ruled out by injecting 1-1.5 ml of non-ionic radiographic contrast (180 mg of 
iohexol per ml) through the integral injection port of the electrode under live 
fluoroscopy. At each treated level, motor stimulation (50 Hz, 1 ms) of less than 0.4 
volts will reproduce the patient's pain and motor stimulation (2 Hz, 1 ms) of less than 
0.6 volts will result in a contraction muscle in the leg. The pulsed radiofrequency will 
be applied for 240 seconds (4 minutes), where the pulses of 45 volts and 20 
milliseconds (ms) will be administered at 2 Hz (pulses per second) and the pulse 
width will be regulated to maintain the temperature at 42 ºC or less. (E-dose = Vary 
Width). The steady-state impedance and current will be measured for each PRF 
epidural treatment at L5 and S1 levels using the 20-gauge, 15 mm active tip.  
After the experimental treatment, the needle and electrode will be removed 
without injecting or any other substance capable of producing pain relief. A sterile 
dressing will be applied over the needle insertion site. The patient will be monitored 
while the sedation is removed, the motor dysfunction of the leg is verified and then 
the patient will be discharged. 
 
 
 
 

 
 
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10. - PRACTICAL CONSIDERATIONS AND ETHICALS ASPECTS 
10.1 General Considerations 
The Clinical Investigation will be conducted under conditions of respect for the 
fundamental rights of the person and the ethical postulates that affect biomedical 
research with human beings, following the international recommendations included 
in the Declaration of Helsinki, and their subsequent revisions. Likewise, the national 
recommendations will be followed in accordance with the guidelines of the Spanish 
Agency of Medicines and Medical Devices.  
During the conduct of this study, the researchers will strictly comply with the 
provisions of this protocol, fully completing the Data Collection Notebook. 
10.2 Informed Consent 
In accordance with the criteria of good clinical practice, the subjects will be duly 
informed of all the details concerning their participation in the study and will freely 
give their consent in writing. 
10.3 About the Participating Staff 
The researchers will follow the Good Clinical Practice guidelines. All information 
collected during the study must be recorded directly in the CRF. Any correction made 
in the CRF must be accompanied by the date and initials of the person who makes 
them. 
15.2.1. Responsibilities 
 
1. Investigator 
The researcher must comply with following obligations: 
• Commit to carry out the study in accordance with what is established in 
its protocol, ensuring that your participation in this study does not alter 
your clinical responsibilities or the normal functioning of the Service to 
which you belong. 
• Inform those responsible for the management of the center to which 
they belong to their participation in the study. 
• Inform research subjects and obtain their consent. 
• Collect, record and notify the data correctly responding to its update 
and quality before the appropriate audits. 
• You must answer any questions about the objectives, basic 
methodology and meaning of the results of the study before the 
scientific and professional community. 

 
 
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• Facilitate the inspections of the health authorities, which will keep the 
study documentation a minimum of 5 years after the presentation of 
the final report. 
• It will be responsible for the information recorded in the CRD being 
accurate, truthful and obtained in the manner indicated in the protocol. 
• The investigator is the only person who can and should know the origin 
of the data collected and associate them with the patient, being 
responsible for not showing in the CRD extra (unclaimed) information 
that can identify the patient (name, DNI / NIF, NASS, CIP, postal 
address, telephone ...). 
• Especially, the researcher must ensure at all times the best possible 
care of the patient, always putting the well-being and safety of his 
patients. 
2. Coordinating Investigator: 
• The coordinating researcher must fulfill all the obligations as a 
researcher of the study and also must sign the protocol and any 
modification thereof together with the promoter, will be responsible 
together with the promoter in the preparation of the monitoring and 
final reports, will contribute to disseminate the results of the study in 
collaboration with the promoter. 
• Send the protocol to the CEIm. 
 
3. Sponsor: 
 
• Will be responsible for ensuring compliance with the relevant legal 
regulations.  
• Sign the protocol and any modification of it with the coordinating 
investigator.  
• Present the study protocol and the follow-up and final reports, within 
the established deadlines and communicate, where appropriate, the 
interruption and the reasons for it.  
• Provide a copy of the protocol and the documents that accredit the 
follow-up of the established procedures to those responsible for the 
entities providing health care services where the study will be carried 
out. 
10.4 Security Devices and Confidentiality 
The information obtained in the present study is confidential, with patients 
accepting, in writing, that researchers and Health Authorities have access to their 
medical records to verify the data or procedures of the study, without violating the 

 
 
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confidentiality of the data compliance with current legislation. In each participating 
centre, the clinical data will be identified by an alphanumeric code, which does not 
allow to identify the personal data of the patients, such as name, initials, address or 
other personal characteristic. Likewise, the confidentiality of the identity of the 
patients would be respected if the data obtained in this study were published.  
The data of the subjects included in the study will be treated in accordance with 
Regulation (EU) 2016/679 of the European Parliament and of the Council of April 27 
2016 and according to the Spanish Law, The Organic Law 3/2018, of December 5, 
Protection of Personal Data and Guarantee of Digital Rights regarding the protection 
of individuals with regard to treatment of personal data and the free circulation of 
these data, and in the other applicable legislation in force regarding the protection of 
personal data. 
11. - ECONOMICAL ASPECTS 
11.1 Insurance Policy 
According with current clinical trial legislation, this clinical trial does not require 
an insurance policy since the devices under study are used under the authorized 
conditions of use and the study does not imply an increase in the risk to the patient. 
12. - PUBLICATIONS RIGHTS 
Principal Investigator shall have the right to publish the results of the Study in any 
abstract, paper, presentation or manuscripts (not limited enumeration).  
Principal Investigator shall give BOSTON SCIENTIFIC a reasonable period of 30 
(thirty days) to review and comment upon an intended publication of Principal 
Investigator regarding the results of the Study prior to publication, to determine if 
any Intellectual Property Rights and/or Confidential Information should be removed. 
BOSTON SCIENTIFIC shall respond promptly in writing to Principal Investigator with 
any comments or objections, setting forth such information in reasonably sufficient 
detail.  
Principal Investigator shall consider BOSTONS’S SCIENTIFIC comments and/or 
objections in good faith and shall cause any and all appropriate changes to be made 
prior to further distribution and publication. 
13. - STATISTIC ANALYSIS 
A descriptive analysis of the categorical variables was performed using absolute 
and determined frequencies; and in the numerical variables, through the mean and 

 
 
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standard or median deviation and 25th and 75th percentiles, according to 
compliance with the assumption of normality. 
The analysis of the main variable, pain difference between baseline measurement 
and 6 months after treatment in the radiofrequency group plus steroids vs steroids, 
will be carried out using a contrast of means with the t-Student or U Mann-Whitney 
test in case of not being able to fulfill the corresponding assumptions. 
The size of the effect is estimated with Cohen's letter, interpreting a Cohen's 
letter <0.01 as "very small", between 0.01 to 0.2 as a "small" effect, around 0.5 an 
"average" effect ", from 0.8 to infinity, a" large "effect, according to the 
categorization of Cohen and Sawilowsky (Cohen, Jacob (1988). Statistical analysis of 
power for behavioral sciences. Routledge; Sawilowsky, S (2009). "New effect size 
rules of thumb". Journal of Modern Applied Statistical Methods. 8 (2): 467–474.). 
If the imbalance is observed between the two groups, linear regression will be 
executed to adjust for variables that are observed unbalanced between them. 
The level of significance has been set at 0.05. The statistical package used is Stata 
/ IC v.15.1. (StataCorp. 2017. Stata Statistical Software: version 15. College Station, 
TX: StataCorp LLC). 
 
14. - BIBLIOGRAPHY 
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31. Ramanavarapu V, Simopoulos TT. Pulsed radiofrequency of lumbar dorsal root 
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radiofrequency treatment on the saphenous nerve in patients with chronic knee pain 
(2011). J Back Musculoskelet Rehabil 24:77-82.  
37. Djibilian Fucci RE, Pascual-Ramírez J, Martínez-Marcos A, Mantecón JM. 
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a novel approach (2013). J Anesth 27:935-8. 
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study with 6 months of follow-up (2010). Reg Anesth Pain Med 35:148-51. 

 
 
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44. Choi HJ, Oh IH, Choi SK, Lim YJ. Clinical outcomes of pulsed radiofrequency 
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Soc 51:281-5. 
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55. Pitcher GM, Henry JL. Governing role of primary afferent drive in increased 
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56. Insausti J, Uriarte E, García-Rueda A, Reig E, Abejon D, Del Pozo C, Perez C. 
Lumbosacral roots radiofrequency with racz catheter. A new approach in selected 
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57. Bhaskar A, Cosman ER Jr. A Novel Technique to Deliver Epidural Pulsed 
Radiofrequency for the Management of Lumbar Radicular Pain – A Case Report. 
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15. - ANEXES 
15.1 Annex I. Information on the Investigator Team  
 
Name 
Centre 
Title 
Agustín Mendiola 
HM Hospitales 
Coordinating/ 
Principal Investigator 
Manuel Agustín Herrero 
H. U. HM Sanchinarro 
Site Principal Investigator 
Sandra Helena Martínez 
H. U. Puerta de Hierro 
Site Principal Investigator 
Moisés Vásquez 
H. U. Rey Juan Carlos 
Site Principal Investigator 
Rogelio Rosado 
H. Fremap 
Site Principal Investigator 
María Ángeles Canós 
H. U. La Fé de Valencia 
Site Principal Investigator 
Pablo López 
H. C. U. Santiago 
Site Principal Investigator 
 
 
 

 
 
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No Pain 
The worst pain imaginable 
15.2 Annex II. Study Forms 
NOTE: All forms will have the following header and footer so that they are perfectly 
identified 
1.- Header: 
“Epidural Pulse Radiofrequency for Treatment of Failed Back Syndrome: Prospective, Randomized, Single-Blind Study” 
Patient ID Number: 
Name: 
Date Of Visit (DD/MM/YYYY): 
Sign: 
2.- Footer: 
Confidentiality: The data of the subjects included in the study will be treated in accordance with Regulation (EU) 2016/679 of the 
European Parliament and of the Council of April 27 2016 and according to the Spanish Law, The Organic Law 3/2018, of December 5, 
Protection of Personal Data and Guarantee of Digital Rights regarding the protection of individuals with regard to treatment of 
personal data and the free circulation of these data, and in the other applicable legislation in force regarding the protection of 
personal data. 
 
15.2.1. 
Visual Analogue Scale (VAS) 
VIAUSAL ANALOGUE SCALE (VAS) OF PAIN 
Sponsor: Fundación Investigación HM Hospitales 
 
Principal Investigator: Dr. Agustín Mendiola de la Osa 
Protocol Code: EPIPUL 
Form Version: 1.0 of 26th of July 2019 
 
Pain assessment 
Instructions: Place a vertical bar (|) in the place of the line that describes the 
average pain that have you felt in the last 7 days. 
 
 
 
PAIN BACK 
 
 
 
Patient marked average (cm): 
 
 

 
 
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15.2.2. 
Oswestry Disability Index (ODI) 
Oswestry Disability Index (ODI) 
Sponsor: Fundación Investigación HM Hospitales  
Principal Investigator: Dr. Agustín Mendiola de la Osa 
Protocol Code: EPIPUL 
Form Version: 1.0 of 26th of July 2019 
Instructions: This questionnaire is designed to provide information on how back 
problems affect your ability to perform daily activities. Complete each section. In each 
one, check only the box that best suits your situation today. 
Section 1: Pain Intensity 
  I have no pain at the moment. [0 points] 
 The pain is very mild at the moment. [1 point] 
 The pain is moderate at the moment. [2 points] 
 The pain is fairly severe at the moment. [3 points] 
The pain is very severe at the moment. [4 points] 
 The pain is the worst imaginable at the moment. [5 points] 
Section 2: Personal Care 
 I can look after myself normally without causing extra pain. [0 points] 
 I can look after myself normally but it is very painful. [1 point] 
 It is painful to look after myself and I am slow and careful. [2 points] 
 I need some help but manage most of my personal care. [3 points] 
 I need help every day in most aspects of self care. [4 points] 
 I do not get dressed, wash with difficulty and stay in bed. [5 points] 
Section 3: Lifting 
 I can lift heavy weights without extra pain. [0 points] 
 I can lift heavy weights but it gives extra pain. [1 point] 
 Pain prevents me from lifting heavy weights off the floor but I can manage if they 
are conveniently positioned, e.g. on a table. [2 points] 

 
 
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 Pain prevents me from lifting heavy weights but I can manage light to medium 
weights if they are conveniently positioned. [3 points] 
 I can lift only very light weights. [4 points] 
I cannot lift or carry anything at all. [5 points] 
Section 4: Walking 
 Pain does not prevent me walking any distance. [0 points] 
 Pain prevents me walking more than one mile. [1 point] 
 Pain prevents me walking more than a quarter of a mile. [2 points] 
 Pain prevents me walking more than 100 yards. [3 points] 
 I can only walk using a stick or crutches. [4 points] 
 I am in bed most of the time and have to crawl to the toilet. [5 points] 
Section 5: Sitting 
 I can sit in any chair as long as I like. [0 points] 
 I can sit in my favourite chair as long as I like. [1 point] 
 Pain prevents me from sitting for more than 1 hour. [2 points] 
 Pain prevents me from sitting for more than half an hour. [3 points] 
 Pain prevents me from sitting for more than 10 minutes. [4 points] 
 Pain prevents me from sitting at all. [5 points] 
Section 6: Standing 
 I can stand as long as I want without extra pain. [0 points] 
 I can stand as long as I want but it gives me extra pain. [1 point] 
 Pain prevents me from standing for more than 1 hour. [2 points] 
 Pain prevents me from standing for more than half an hour. [3 points] 
 Pain prevents me from standing for more than 10 minutes. [4 points] 
 Pain prevents me from standing at all. [5 points] 
Section 7: Sleeping 

 
 
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 My sleep is never disturbed by pain. [0 points] 
 My sleep is occasionally disturbed by pain. [1 point] 
 Because of pain I have less than 6 hours sleep. [2 points] 
 Because of pain I have less than 4 hours sleep. [3 points] 
 Because of pain I have less than 2 hours sleep. [4 points] 
 Pain prevents me from sleeping at all.  [5 points] 
Section 8: Sex Life (if applicable) 
 My sex life is normal and causes no extra pain. [0 points] 
 My sex life is normal but causes some extra pain. [1 point] 
 My sex life is nearly normal but is very painful. [2 points] 
 My sex life is severely restricted by pain. [3 points] 
 My sex life is nearly absent because of pain. [4 points] 
 Pain prevents any sex life at all. [5 points] 
Section 9: Social Life 
 My social life is normal and causes me no extra pain. [0 points] 
 My social life is normal but increases the degree of pain. [1 point] 
 Pain has no significant effect on my social life apart from limiting my more 
energetic interests, e.g. sport, etc. [2 points] 
 Pain has restricted my social life and I do not go out as often. [3 points] 
 Pain has restricted social life to my home. [4 points] 
 I have no social life because of pain. [5 points] 
Section 10: Traveling 
 I can travel anywhere without pain. [0 points] 
 I can travel anywhere but it gives extra pain. [1 point] 
 Pain is bad but I manage journeys over two hours. [2 points] 
 Pain restricts me to journeys of less than one hour. [3 points] 

 
 
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 Pain restricts me to short necessary journeys under 30 minutes. [4 points] 
 Pain prevents me from travelling except to receive treatment. [5 points] 
Douleur Neuropathique 4 questions (DN4) 
Douleur Neuropathique 4 Questions (DN4) 
Sponsor: Fundación Investigación HM Hospitales  
Principal Investigator: Dr. Agustín Mendiola de la Osa 
Protocol Code: EPIPUL 
Form Version: 1.0 of 26th of July 2019 
Instructions: Answer the four questions below with Yes or No for each item: 
Question 1: dose your pain present one or more of the following characteristics? 
1. Pain feels like burning 
YES   /   NO 
2. Sensation of painful cold  
YES   /   NO 
 
3. Pain feels like electric shocks 
YES   /   NO 
Question 2: in the same area, is your pain associated to one or more symptoms? 
4. Tingling 
YES   /   NO 
5. Pins and needles 
YES   /   NO 
6. Numbness 
YES   /   NO 
7. Itching 
YES   /   NO 
(Now your doctor will perform a physical examination) 
Question 3: in is the pain located in an area where the exam unveils? 
8. Hypoesthesia to touch? 
YES   /   NO 
9. Hypoesthesia to pinprick? 
YES   /   NO 
Question 4: is the pain provoked or increased by 
10. Brushing?  
YES   /   NO  
 PATIENT SCORE:  
 

 
 
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15.2.3. 
Short Form Health Survey (SF-12) 
SHORT FORM HEALTH SURVEY (SF-12) 
Sponsor: Fundación Investigación HM Hospitales  
Principal Investigator: Dr. Agustín Mendiola de la Osa 
Protocol Code: EPIPUL 
Form Version: 1.0 of 26th of July 2019 
This survey asks for your views about your health. This information will help keep 
track of how you feel and how well you are able to do your usual activities. Please 
answer every question by marking one box. If you are unsure about how to answer, 
please give the best answer you can. 
 1. In general would you say your health is: 
 Excellent 
 Very Good 
 Good 
 Fair 
 The Poor 
The following questions are about activities you might do during a typical day. Does 
your health now limit you in these activities? If so, how much? 
2. Moderate activities, such as moving a table, pushing a vacuum cleaner, cowling, or 
playing golf: 
 Yes, limited a lot 
 Yes, limited a little 
 No, not limited at all 
3. Climbing several flights of stairs: 
 Yes, limited a lot 
 Yes, limited a little 
 No, not limited at all 
During the past week, have you had any of the following problems with your work or 
other regular daily activities as a result of physical health? 
4. Accomplished less than you would like: 

 
 
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 Yes 
 No 
5. Were limited in the kind of work or other activities 
 Yes 
 No 
During the past week, have you had any of the following problems with your work or 
other regular daily activities as a result of any emotional problems (such as feeling 
depressed or anxious)? 
6. Accomplished less than you like: 
 Yes 
 No 
7. Didn’t do work or other activities as carefully as usual: 
 Yes 
 No 
8. During the past week, how much did pain interfere with your normal work 
(including both work outside the home and housework)? 
 Not at all 
 A little bit 
 Moderately 
 Quite a bit 
 Extremely 
These questions are about how you feel and how things have been with you during 
the past week. For each question, please give the one answer that comes closest to 
the way you have been feeling. How much of the time during the past week 
9. Have you felt calm and peaceful? 
 All of the time 
 Most of the time 
 A good bit of the time 

 
 
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Epidural Pulsed Radiofrequency versus Epidural Steroids Injection for Treatment of 
Failed Back Syndrome: A Prospective, Randomized, Single-Blind and Multicenter Study 
CONFIDENTIAL 
 Some of the time 
 A little of the time 
 None of the time 
10. Did you have a lot of energy? 
 All of the time 
 Most of the time 
 A good bit of the time 
 Some of the time 
 A little of the time 
 None of the time 
11. Have you felt downhearted and blue? 
 All of the time 
 Most of the time 
 A good bit of the time 
 Some of the time 
 A little of the time 
 None of the time 
12. During the past week, how much of the time has your physical health or 
emotional problems interfered with your social activities (like visiting with friends, 
relatives, etc.)? 
 All of the time 
 Most of the time 
 A good bit of the time 
 Some of the time 
 A little of the time 
 None of the time 

 
 
EPIPUL V1.4 - 11th of February 2020/Fourth revision and approval 
Page 44 of 44 
 
Epidural Pulsed Radiofrequency versus Epidural Steroids Injection for Treatment of 
Failed Back Syndrome: A Prospective, Randomized, Single-Blind and Multicenter Study 
CONFIDENTIAL 
15.2.4. 
Short Form Health Survey (SF-12) 
Patient General Impression of Improvement (PGI-I)  
Sponsor: Fundación Investigación HM Hospitales  
Principal Investigator: Dr. Agustín Mendiola de la Osa 
Protocol Code: EPIPUL 
Form Version: 1.0 of 26th of July 2019 
 
Since the beginning of the study, my general state of health 
 Very much improved 
 Much improved 
 Minimally improved 
 No change 
 Minimally worse 
 Very much worse 
15.2.5. 
Subject Satisfaction 
SUBJECT SATISFACTION 
Sponsor: Fundación Investigación HM Hospitales  
Principal Investigator: Dr. Agustín Mendiola de la Osa 
Protocol Code: EPIPUL 
Form Version: 1.0 of 26th of July 2019 
 
How satisfied are you with the treatment? 
 Very satisfied 
 Satisfied 
 Not sure 
 Dissatisfied 
 Very dissatisfied