ReActiv8 Implantable Neurostimulation System for Chronic Low Back Pain (ReActiv8-B)
Phase: NA
Conditions: Chronic Low Back Pain
Sponsor: Mainstay Medical

Clinical Investigation Plan – ReActiv8-B 
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from Mainstay Medical and are not to be used in any unauthorized way. 
Page 1 of 84 
Document Number 950057, Rev. E 
25-MAR-2017 
 
 
 
 
Clinical Investigation Plan 
(ReActiv8-B) 
 
A Clinical Trial under an Investigational Device Exemption (IDE) 
 
ReActiv8 Implantable Neurostimulation System 
for Chronic Low Back Pain 
 
Sponsor 
MML US Inc. 
6601 Shingle Creek Parkway 
Brooklyn Center, MN 55430 
Document Number 950057, Rev. E 
25-MAR-2017 
NCT02577354 
 

 Clinical Investigation Plan – ReActiv8-B 
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from Mainstay Medical and are not to be used in any unauthorized way. 
Page 2 of 84 
Document Number 950057, Rev. E 
25-MAR-2017 
Revision History 
Rev 
Change Description 
Effective 
Date 
A 
Initial Release to production 
27-Aug-2015 
B 
Exclusion Criteria:  
• 
Minor clarification to the wording for financial gain 
exclusion 
• 
Removed the compliance exclusion for the pain 
diary 
Updated Product modifications and product additions 
Updated Statistically section to match updated SAP which 
includes details on the interim analysis as requested from the 
FDA 
Modified the medication collection of rescue medications for 
other pain conditions as recommended by the FDA 
Table 5 Study Completion plan updated on availability of 
product use after study 
Clarification that the telephone call prior to visits could also be 
done electronically 
Clarification that the trainers for the PIT will follow a plan for 
training and PIT training materials will be developed by the 
qualified trainers and used consistently at each site  
Minor typographical errors and inconsistencies corrected 
throughout document 
10-Dec-2015 
C 
Exclusion Criteria:  
• 
Minor clarification to the wording for pathology seen on 
MRI (see Eligibility Criteria in Table 1 and sections 5.2 and 
10.1.3). 
• 
Minor clarification to the wording for prior diagnosis of 
lumbar vertebral compression (see Eligibility Criteria in 
Table 1 and section 5.2). 
Timing of implant visit from baseline revised from 30 days to 
45 days to allow sufficient time for diagnostic tests and 
independent MRI assessment to be completed and surgery 
scheduled (see Study Schedule in Table 1 and section 6.2). 
Clarified that the Percent Pain Relief (PPR) metric is obtained 
by a question asked to the Subject by the Investigator or 
Coordinator (and not via a questionnaire). See section 4.6.4. 
05-Sep-2016 

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Document Number 950057, Rev. E 
25-MAR-2017 
Sponsor address change and overall study principal 
investigator address change (see section 11). 
Minor typographical errors and inconsistencies corrected 
throughout document. 
D 
Removed the Upper Limit for age of subjects in the Trial.  
 
Revised to reflect the requirement for a Psychological 
Assessment for every subject prior to inclusion in the Trial.  
 
Revised to clarify that an Informed consent may be signed by 
an Investigator OR the investigator's delegate. 
 
Added a statement that the Study PI conducts a final review 
for all subjects to ensure inclusion/exclusion requirements are 
satisfied.  
 
Added the ReActiv8 Lead Models 8145/8165 to the ReActiv8 
Product Family.  
31-JAN-2017 
E 
Updated age limit for subjects in the Trial to ≤ 75 years old. 
25-MAR-2017 
 
 

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Document Number 950057, Rev. E 
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Investigator Signature Page 
Investigator Acknowledgement Signature: 
 
I have received and reviewed this Clinical Investigational Plan. I will conduct the Trial as 
described. 
 
_________________________________ 
___________ 
 
Investigator’s Name (print) 
Site Number 
 
 
_________________________________ 
___________ 
Investigator’s Signature 
Date 

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Document Number 950057, Rev. E 
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Table of Contents 
1. Study Purpose ........................................................................................................ 9 
2. Overview ................................................................................................................. 9 
2.1. 
Chronic Low Back Pain ................................................................................................... 9 
2.2. 
ReActiv8 ........................................................................................................................ 10 
2.3. 
Discussion on Outcome Measures ................................................................................ 11 
2.4. 
Overall Synopsis of the Clinical Investigation................................................................. 12 
3. The ReActiv8 Therapy .......................................................................................... 21 
3.1. 
Summary of ReActiv8 .................................................................................................... 21 
3.2. 
Surgical Implantation and Device Activation .................................................................. 22 
3.3. 
Physician Training ......................................................................................................... 23 
4. Study Design ......................................................................................................... 24 
4.1. 
Hypothesis .................................................................................................................... 24 
4.2. 
Proposed Indications for Use for ReActiv8 .................................................................... 24 
4.3. 
Study Population ........................................................................................................... 24 
4.4. 
Study Size and Duration ................................................................................................ 24 
4.4.1. 
Investigational Sites ....................................................................................................... 24 
4.4.2. 
Surgical Roll In Phase ................................................................................................... 25 
4.4.3. 
Study Duration ............................................................................................................... 25 
4.5. 
Assessment of Lumbar Multifidus Dysfunction ............................................................... 25 
4.6. 
Outcome Measures ....................................................................................................... 26 
4.6.1. 
Low Back Pain Visual Analog Scale (VAS) ................................................................... 26 
4.6.2. 
ODI ................................................................................................................................. 27 
4.6.3. 
EQ-5D ............................................................................................................................ 27 
4.6.4. 
Percent Pain Relief (PPR) ............................................................................................. 28 
4.6.5. 
SGIC .............................................................................................................................. 28 
4.6.6. 
Clinical Global Impression ............................................................................................. 28 
4.6.7. 
Resolution of Back Pain ................................................................................................. 28 
4.7. 
Clinical Trial Endpoints .................................................................................................. 29 
4.7.1. 
Primary Endpoint – Low Back Pain VAS ....................................................................... 29 
4.7.2. 
Secondary Efficacy Endpoints ....................................................................................... 30 
4.7.3. 
Primary Safety Assessment ........................................................................................... 31 
4.7.4. 
Supporting Safety Analysis ............................................................................................ 31 
4.7.5. 
Supporting Analyses ...................................................................................................... 31 
4.7.6. 
Health Economics .......................................................................................................... 32 
4.8. 
Control Arm ................................................................................................................... 33 
4.9. 
Blinding and Blinding Assessment ................................................................................. 34 
4.10. Crossover ...................................................................................................................... 35 
4.11. Data Collection .............................................................................................................. 35 
4.12. Stimulation Compliance ................................................................................................. 35 
4.13. Statistical Plan ............................................................................................................... 36 
4.14. Trial Schema ................................................................................................................. 37 
5. Subject Selection and Withdrawal ...................................................................... 39 
5.1. 
Inclusion Criteria ............................................................................................................ 39 
5.2. 
Exclusion Criteria .......................................................................................................... 39 
5.3. 
Other Therapy During the Trial ...................................................................................... 42 

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Document Number 950057, Rev. E 
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5.3.1. 
Medication ...................................................................................................................... 42 
5.3.2. 
Physiotherapy & Exercise .............................................................................................. 43 
5.3.3. 
Other Devices or Therapy .............................................................................................. 43 
6. Subject Contact and Data Collection Schedule ................................................. 44 
6.1. 
Visit 1: Informed Consent, Baseline Data, Inclusion Decision ........................................ 44 
6.2. 
Visit 2: Implant Procedure.............................................................................................. 45 
6.3. 
Visit 3: Post-Implant 7 -0+10 Days ................................................................................ 46 
6.4. 
Visit 4: Randomization & Activation Visit 14 ± 3 days Post Implant ................................ 46 
6.5. 
Visit 5: 14±7 Days Post Randomization ......................................................................... 47 
6.6. 
Visit 6: 45±7 Days Post Randomization ......................................................................... 47 
6.7. 
Visit 7: 75±10 Days Post Randomization ....................................................................... 48 
6.8. 
Visit 8: 120 -0/+20 Days Post Randomization ................................................................ 49 
6.9. 
Visit 8a: Crossover and Activation ................................................................................. 49 
6.10. Visit 9: 180 ± 30 Days Post Randomization ................................................................... 50 
6.11. Visits 10: 240 ± 30 Days Post Randomization ............................................................... 50 
6.12. Visits 11: 12 Months 0-30/+60 Days Post Randomization .............................................. 51 
6.13. Annual Follow Up .......................................................................................................... 51 
6.14. Unscheduled Visits ........................................................................................................ 52 
6.15. Telephone Calls or Electronic contact ........................................................................... 52 
6.16. Revision/Explant Procedure .......................................................................................... 53 
7. Anticipated Benefits and Risks ........................................................................... 54 
7.1. 
Anticipated Benefits ....................................................................................................... 54 
7.2. 
Anticipated Risks ........................................................................................................... 54 
7.3. 
Risk Minimization .......................................................................................................... 56 
8. Safety ..................................................................................................................... 57 
8.1. 
Adverse Event Reporting ............................................................................................... 58 
8.2. 
Adverse Event Outcome Status ..................................................................................... 59 
8.3. 
Device Deficiencies ....................................................................................................... 59 
8.4. 
Subject Deaths .............................................................................................................. 59 
9. Data Management ................................................................................................. 61 
9.1. 
Study Assessments ....................................................................................................... 61 
9.1.1. 
Medical History .............................................................................................................. 61 
9.1.2. 
Subject Screening/Baseline ........................................................................................... 61 
9.1.3. 
Depression Anxiety Stress Scale (DASS21) ................................................................... 62 
9.1.4. 
Surgical Procedure ........................................................................................................ 62 
9.1.5. 
Post-Operative Evaluation ............................................................................................. 62 
9.1.6. 
Physical Exam and Surgical Site Exam (Post Implant) ................................................. 62 
9.1.7. 
Oswestry Disability Index ............................................................................................... 62 
9.1.8. 
Low Back Pain VAS ....................................................................................................... 62 
9.1.9. 
Medication ...................................................................................................................... 63 
9.1.10. 
Treatment Satisfaction Questionnaire ........................................................................... 63 
9.1.11. 
Subject Global Impression of Change ........................................................................... 63 
9.1.12. 
Clinical Global Impression – Global Improvement......................................................... 63 
9.1.13. 
EQ-5D ............................................................................................................................ 64 
9.1.14. 
Adverse Events .............................................................................................................. 64 
9.1.15. 
Device Deficiency .......................................................................................................... 64 
9.2. 
Management of Protocol Deviations .............................................................................. 64 
9.3. 
Informed Consent .......................................................................................................... 65 

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Document Number 950057, Rev. E 
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9.4. 
Subject Classification .................................................................................................... 65 
9.5. 
Subject Data Confidentiality ........................................................................................... 65 
9.6. 
Record Keeping ............................................................................................................. 66 
10. Study Management ............................................................................................... 68 
10.1. Committees and Independent Review ........................................................................... 68 
10.1.1. 
Data Monitoring Committee ........................................................................................... 68 
10.1.2. 
Adjudication Committee ................................................................................................. 68 
10.1.3. 
Independent Assessment of Surgical Candidacy .......................................................... 68 
10.2. Study Principal Investigator Review ............................................................................... 68 
10.3. Procedures to Amend the Clinical Investigation Plan ..................................................... 68 
10.4. Device Accountability .................................................................................................... 69 
10.5. Labeling ......................................................................................................................... 69 
10.6. Data Monitoring Plan ..................................................................................................... 70 
10.7. Sponsor Responsibilities ............................................................................................... 70 
10.8. Role of the Sponsor Representatives ............................................................................ 71 
10.9. Clinical Investigators ...................................................................................................... 71 
10.10. Investigator Selection .................................................................................................... 72 
10.11. Publication Policy .......................................................................................................... 73 
10.12. Payment of Subjects ...................................................................................................... 73 
10.13. Maintaining Compliance ................................................................................................ 73 
10.13.1. Study Monitoring ............................................................................................................ 73 
10.13.2. Review of Submitted Data ............................................................................................. 74 
10.13.3. Securing Compliance ..................................................................................................... 74 
10.14. Study Completion .......................................................................................................... 74 
10.15. Suspension or Premature Termination of the Trial ......................................................... 74 
11. Administrative Data .............................................................................................. 77 
11.1. Name and Address of the Sponsor ................................................................................ 77 
11.2. Investigators .................................................................................................................. 77 
11.3. Data Monitoring Committee ........................................................................................... 77 
11.4. Adjudication Committee ................................................................................................. 77 
11.5. Clinical Research Organizations (CROs) ....................................................................... 78 
11.6. Statements of Compliance ............................................................................................. 78 
Appendix 1: Acronyms and Definitions .................................................................... 79 
Appendix 2: Bibliography ........................................................................................... 82 
Table of Figures 
Figure 1: Conducting the Prone Instability Test .........................................................................26 
Figure 2: Subject Global Impression of Change (SGIC) Questionnaire .....................................28 
Figure 3: Clinical Global Impression Questionnaire ...................................................................28 
Figure 4: Blinding Assessment Questionnaire ...........................................................................35 
Figure 5: Trial Schema ..............................................................................................................37 
Figure 6: Treatment Satisfaction Questionnaire ........................................................................63 
Table of Tables 
Table 1: Synopsis of Clinical Investigation ................................................................................13 
Table 2: Summary Data Collection Schedule ............................................................................38 

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Document Number 950057, Rev. E 
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Table 3: Benzodiazepine Equivalents .......................................................................................42 
Table 4: Adverse Event Relatedness Categories ......................................................................57 
Table 5: Study Completion Plan ................................................................................................76 
 

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Document Number 950057, Rev. E 
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1. 
Study Purpose 
To evaluate the safety and efficacy of ReActiv8 for the treatment of adults with Chronic Low 
Back Pain and no prior surgery when used in conjunction with medical management.  
2. 
Overview 
MML US Inc. (the Sponsor) is a wholly owned subsidiary of Mainstay Medical Limited (based in 
Ireland (“Mainstay”). Mainstay has developed an implantable medical device designed as 
therapy for people with chronic low back pain (CLBP). The device, called ReActiv8®, consists of 
two implantable leads with four electrodes each, configured to deliver bilateral electrical 
stimulation to the medial branch of the dorsal ramus nerves as they cross the transverse 
process at L3 to elicit bilateral contraction of the lumbar multifidus muscles (LM). The leads are 
coupled to a battery powered implantable pulse generator (IPG) which is activated by an 
external Activator, and is programmed via a programmer. Several accessories are included as 
part of the system, for example to facilitate the surgical procedure. 
The therapy delivered by the ReActiv8 was explored with a European Feasibility Study in 2011 
to 2013 using “off the shelf” general purpose neurostimulation devices from other 
manufacturers, and results have been published.1 A report of that Study is included in the 
Report of Prior Investigations. 
ReActiv8 is being investigated under an ongoing clinical trial to generate data for a submission 
for CE Mark approval in Europe. Subjects are enrolled at several sites in Australia and Europe. 
Details of this trial can be found at http://clinicaltrials.gov/show/NCT01985230 and the interim 
results of the ReActiv8-A clinical investigation are included in the Report of Prior Investigations 
and the Investigators Brochure.  
2.1. Chronic Low Back Pain 
This section is a summary of the scientific background of the ReActiv8. 
Low back pain is usually defined as pain and discomfort, localized below the costal margin and 
above the inferior gluteal fold, with or without referred leg pain.2,3 Chronic Low Back Pain 
(CLBP) is usually defined as back pain for at least 3 months. The NIH Task Force on Research 
Standards for Chronic Low Back Pain recommended4 that Chronic Low Back Pain be defined as 
a back pain problem that has persisted for at least 3 months and has resulted in pain on at least 
half the days in the past 6 months. 
Chronic low back pain is a major health problem, and the World Health Organization reports that 
“Low back pain is the most prevalent of musculoskeletal conditions; it affects nearly everyone at 
some point in time and about 4–33% of the population at any given point”5 and back pain is the 
number one cause of years lived with disability worldwide in 2013.6 There are many publications 
on the epidemiology7 of back pain including prevalence,8,9,10 natural history, demographics, and 
country by country variability. 
People with acute low back pain and associated disability usually improve rapidly within weeks, 
but pain and disability typically continue, and recurrences are common.11 Although most 
episodes of acute back pain resolve within 3 months, “recovery after 12 weeks is slow and 
uncertain. Fewer than half of those individuals disabled for longer than 6 months return to work 
and, after 2 years of absence from work, the return-to-work rate is close to zero.”12 Like many 
chronic conditions, the costs are driven by the small proportion of the population who have been 

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Document Number 950057, Rev. E 
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sick for the longest period – for back pain, patients with disability >1 year account for 5% of 
cases, but 65% of costs.13,14 
Although there has been a lot of attention and investment applied to surgical treatments for low 
back pain, only approximately 20% of patients are suitable surgical candidates.15 The remaining 
patients are sometimes referred to as having “non-specific low back pain” (NSLBP) or “axial low 
back pain” (ALBP). There are European clinical practice guidelines for chronic NSLBP2 and UK 
guidelines for management of patients with persistent CLBP (published by the National Institute 
for Clinical Excellence - NICE).16 US guidelines for acute and chronic low back pain are similar 
to the European guidelines.17 
Exercise therapy is frequently prescribed for NSLBP, but the effectiveness of exercise therapy 
for acute back pain is negligible.18 Systematic reviews of the literature19,20 concerning therapies 
for chronic low back pain show that exercise is generally ineffective, other than certain types of 
exercise therapy which can be effective in a small subset of patients.  
Many non-invasive conservative therapies have been tried with modest or no success, and 
several reviews are available.21 Therapies include lumbar extensor strengthening exercises;22 
watchful waiting (i.e., no therapy),23 traction therapy,24 the McKenzie Method of exercise 
therapy,25 various types of energy application including ultrasound, TENS,26 osteopathic 
therapy,27 and thermotherapy,28 and lumbar stabilization exercises.29 
Following failure of conservative therapy for CLBP, “usual care” or “conventional medical 
management” for CLBP usually consists of coping mechanisms for pain, and pain medications 
(often opioids), which are often increased during the episodic flare-ups of pain.  
2.2. ReActiv8 
Arthrogenic muscle inhibition (AMI)30 is the physiological mechanism by which pain in a skeletal 
joint disrupts the motor control to the muscles that stabilize the joint – often observed in the 
quadriceps post knee surgery. A similar mechanism underlies some types of chronic low back 
pain, with disruption to the motor control of the key stabilizing muscles – the lumbar multifidus. 
Evidence includes diminished EMG activity in back pain patients31 and delayed reflex response 
of the LM to perturbations.32 Pain alters the magnitude of activation of deep LM during certain 
types of activity.33 Ultrasound imaging evidence of reduced neural drive in back pain patients 
includes diminished cross sectional area with contraction,34 reduced ability to cause a muscle 
thickness change on command,35 and altered contraction patterns with changes in posture.36 
Published studies show that subject initiated contraction of the lumbar multifidus with ultrasound 
guided biofeedback motor control physical therapy exercises can lead to improvements in back 
pain, but this approach has not been adopted due to practical challenges, economic difficulties, 
and patient compliance issues. The mechanism of action is believed to be restoration of motor 
control of the lumbar multifidus, thereby leading to rehabilitation of the muscle, improved spine 
stability and reduction in back pain. 
Electrical stimulation to restore motor control has been successfully used with other skeletal 
muscles. In particular, stimulation via superficial (skin) electrodes over the motor point of the 
quadriceps can restore neural drive and allow rehabilitation of the muscle in patients following 
total knee arthroplasty37 or other surgical procedures.38,39 Painful knee osteoarthritis can be 
treated without surgery but may also lead to pain mediated inhibition of neural drive to the 
quadriceps, which can be treated effectively with electrical stimulation.40  
The ReActiv8 has been designed to incorporate the principles of these prior approaches. 
Bilateral electrical stimulation of the medial branch of the dorsal ramus nerve that innervates the 

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lumbar multifidus is delivered episodically (10 seconds “on” followed by 20 seconds “off”, for 30 
minutes, during two sessions per day). Previous experience with the therapy in the European 
Feasibility Study showed that many subjects can perceive the muscle contractions, and report 
the muscle contractions as “soothing” or “pleasurable.” 
The intent to implant leads bilaterally and give bilateral stimulation is based on published 
research that indicates that multifidus dysfunction (atrophy) is likely to be bilateral even if the 
patient reports unilateral pain.  
Beneck showed41 that in people with chronic unilateral low back pain (<1 year) multifidus 
atrophy is bilateral with no difference in multifidus volume between the painful and non-painful 
sides. 
D’Hooge explored changes in muscle fiber type of the multifidus erector spinae, quadratus 
lumborum and psoas using MRI imaging42 and showed a conversion of (only) multifidus muscle 
fiber type towards the glycolytic (anaerobic) muscle spectrum bilaterally in patients with 
unilateral low back pain, and the changes persist after resolution of the pain. 
Dickx showed43 in an experimental human model that using hypertonic saline to induce 
unilateral pain at one segmental level resulted in bilateral dysfunction of the multifidus muscle 
and at multiple segmental levels. 
Furthermore, the incremental risk of bilateral stimulation over unilateral stimulation is judged to 
be low – as the primary risk is associated with the surgical procedure itself and the incremental 
time for placement of the second lead is approximately 15 minutes. Conversely, implantation of 
one lead only (unilateral stimulation) exposes the subject to the risk of an additional surgical 
procedure if it is found that a second lead is needed for bilateral stimulation. Therefore, bilateral 
treatment is preferred over unilateral treatment. 
2.3. Discussion on Outcome Measures 
Since the primary indication for ReActiv8 is to provide pain relief, the primary endpoint is based 
on a valid outcome measure for pain. 
Many outcome measures have been used in clinical trials for pain, and specifically for low back 
pain, and more specifically for chronic low back pain. There are multiple recommendations from 
the IMMPACT group (Initiative on Methods, Measurement, and Pain Assessment in Clinical 
Trials)44,45,46 which are generalizable to many trials for treatment of pain. The Visual Analog 
Scale (VAS) or the Numerical Rating Scale (NRS) are well accepted measures of pain. VAS is a 
widely used outcome measure in assessing pain due to the documented reliability, ease in 
administration and the minimal training requirements to administer the VAS tool.47 
For this Trial, the primary endpoint is a comparison of responder rates between Treatment and 
Control groups, where a “responder” is a subject with ≥30% reduction from baseline in average 
low back pain VAS recalled for the previous 7 days, without any increase from baseline in pain 
medication and/or muscle relaxants (pain medications) prescribed and taken in the two weeks 
prior to the Primary Endpoint Assessment Visit. 
Oswestry Disability Index (ODI) is a disease specific assessment of the disabling effects of back 
pain.48 The ODI covers 1 item on pain and 9 items on activities of daily living (personal care, 
lifting, walking, sitting, standing, sleeping, sex life, social life, and traveling). ODI is reported as a 
score from 0 to 100%. Recent CLBP studies use a disability index as the primary outcome 
measure rather than pain.49,50 In this Trial ODI is an important secondary endpoint. 

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2.4. Overall Synopsis of the Clinical Investigation 
The Clinical Investigation is an international, multi-center, prospective, randomized, sham 
controlled, blinded Trial with an adaptive statistical design. The Trial is powered for statistical 
significance and the Statistical Analysis Plan is provided in a separate document and 
summarized herein. A synopsis in tabular form is shown in Table 1. 
All Subjectsa who satisfy the baseline criteria are implanted with the ReActiv8, and then at the 
Randomization Visit are instructed to deliver stimulation during two 30-minute sessions 
(morning and evening) per day. Subjects are randomized (1:1) to the Treatment or Control Arm 
at the Randomization Visit. 
Subjects randomized to the Treatment Arm of the study will have ReActiv8 programmed to 
deliver stimulation at a Subject-appropriate level (the Treatment group). Determination of the 
Subject appropriate level is described in the Implant and Programming Manual. Subjects in the 
Treatment group may or may not feel sensations during stimulation. 
Subjects randomized to the Control Arm will have ReActiv8 programmed to deliver minimal 
stimulation (the Control group). Subjects in the Control group may or may not feel sensations 
during stimulation. 
All subjects will have automatic electrical impedance measurement of electrodes performed 
immediately prior to each stimulation session. 
Thus, with this design, all subjects receive some electrical stimulation. The Informed Consent 
will advise subjects that electrical stimulation will be delivered, and subjects may or may not feel 
something associated with the stimulation. Subjects will also be advised in the Informed 
Consent that they will be randomized to one of two different treatment regimes. 
Subjects will be eligible for enrollment if they have chronic low back pain that has persisted >90 
days that has resulted in pain in at least half of the days in the 12 months prior to the Baseline 
Visit, despite medical management including at least pain medications and one attempt of a 
prescribed physical therapy program for low back pain, and satisfy the other eligibility criteria. It 
is likely that subjects will have tried and failed other conservative treatment options including 
one or more of chiropractic, massage, cognitive behavioral therapy, medial branch rhizotomy, 
nerve blocks, steroid injections, acupuncture or lumbar supports. All treatments that have been 
tried will be recorded. 
All endpoints are assessed at 120 days post randomization (at the Primary Endpoint 
Assessment Visit). 
Compliance with instructions for stimulation delivery will be assessed from data stored in the 
ReActiv8 IPG, which records the start and stop time of each stimulation session. 
The Primary Efficacy Endpoint is a comparison of responder rates of pain where a “responder” 
is a Subject with ≥30% reduction from baseline in average low back pain VAS, without any 
increase in pain medication and/or muscle relaxants prescribed and taken in the two weeks 
prior to the Primary Endpoint Assessment Visit. 
Several secondary endpoints will be assessed, including change in ODI, change in EQ-5D 
Quality of Life, change in Percent Pain Relief, and Subject Global Impression of Change, all 
assessed as a difference between baseline and the Primary Endpoint Assessment Visit. 
 
a  
In this Clinical Investigation Plan, the term used is “subject” instead of “patient” in line with the suggestions of ISO 14155. 
The terms should be considered as synonymous. 

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Subgroups will be also analyzed based on Subject characteristics (e.g.: BMI) and by site. 
Several other endpoints will be analyzed on an exploratory basis. 
Safety will be assessed by collecting data on the rate of all serious device and/or procedure 
related adverse events in all enrolled Subjects. Adverse event data will be collected at each visit 
beginning with the Baseline Visit. The Safety Cohort consists of all enrolled Subjects in whom 
implant was attempted or successful. A separate analysis will be conducted of the Safety Cohort 
without Subjects included in the Surgical Roll In Cohort. 
Table 1: Synopsis of Clinical Investigation 
Study Purpose 
To evaluate the safety and efficacy of ReActiv8 for the treatment of adults 
with Chronic Low Back Pain and no prior spine surgery when used in 
conjunction with medical management. 
Indication For 
Use 
ReActiv8 is an adjunct to medical management in adults with Chronic Low 
Back Pain for relief of pain in subjects who have failed at least medical 
management and physical therapy. 
Study Device 
Mainstay ReActiv8  
Study Design 
International, multi-center, prospective, randomized, sham controlled, blinded 
Trial with an adaptive statistical design. Subjects are blinded, investigators 
are blinded, and the assessment of primary endpoint data is blinded. 
Treatment Arm 
ReActiv8 implanted and configured to deliver stimulation at a Subject-
appropriate level and Subjects instructed to deliver stimulation in two 
30-minute sessions per day (the Treatment group). 
Control Arm 
ReActiv8 implanted and configured to deliver minimal stimulation, and 
Subjects instructed to deliver stimulation in two 30-minute sessions per day 
(the Control group). 
Randomization 
Subjects meeting all eligibility criteria who have been implanted with ReActiv8 
will be randomized post-implant to either the Treatment group or the Control 
group. Randomization will be performed according to a random permuted 
block design stratified by clinical site with a 1:1 allocation ratio for Treatment 
vs. Control. 
Anticipated 
Sample Size 
Initial estimate: 128 randomized Subjects implanted with ReActiv8 in the 
intent to Treat cohort of the study, plus up to 80 Subjects implanted in the 
Surgical Roll In group. 
An adaptive statistical design using a single interim look will be used for 
sample size re-estimation when at least 50% of the implanted Subjects have 
completed the Primary Endpoint Assessment Visit. 
Up to 800 Subjects will be enrolled to account for screen failures prior to 
implant, Surgical Roll In, drop outs, and possible increase in numbers for the 
intent to treat analyses after the interim look. 
Anticipated 
Number of Sites 
There will be up to 40 Investigational sites performing implants. Each site will 
have a Site Principal Investigator who may or may not be the implanting 
physician. One or more Sub-investigators per site (or affiliated site if the 
affiliated site has a different Ethics Committee or IRB) may be used for 
example for device implantation and Subject recruitment. 

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Surgical 
Training and 
Surgical Roll In 
All physicians who will implant any portion of the system will be trained as 
outlined in the Training Strategy. Following training, up to the first two 
Subjects implanted by the same physician may be prospectively included in a 
Surgical Roll In group. Subjects included in the Surgical Roll In group will be 
randomized to Treatment or Control with a single group randomization, and 
be analyzed as a separate cohort (the Surgical Roll In Cohort). 
Crossover and 
Open Label 
Phase 
Following endpoint assessment at the Primary Endpoint Assessment Visit: 
• 
Subjects randomized to the Control Arm will have ReActiv8 configured 
to deliver stimulation at a Subject-appropriate level, and Subjects will 
be instructed to deliver stimulation in two 30-minute sessions per day. 
Once the Control group has crossed over, it will be referred to as the 
Crossover group.  
• 
All Subjects in the Treatment group will be advised to continue to use 
their devices for two 30-minute sessions per day. 
• 
All Subjects will be permitted to change their medications 
Primary Efficacy 
Endpoint 
The Primary Efficacy Endpoint is a comparison of responder rates between 
Treatment and Control groups, where a “responder” is a Subject with ≥30% 
reduction from baseline in average low back pain VAS without any increase 
in pain medication and/or muscle relaxants prescribed and taken in the two 
weeks prior to the Primary Endpoint Assessment Visit. 
Secondary 
Efficacy 
Endpoints 
The hypotheses will be tested utilizing an overall Type I error of 5%. The 
overall Type I error will be maintained by utilizing Hochberg’s method to test 
the collection of the first five secondary objectives. These will be tested only if 
the primary efficacy endpoint is met. 
1. Comparison of change from baseline in ODI between Treatment and 
Control groups at the Primary Endpoint Assessment Visit 
2. Comparison of change from baseline in EQ-5D between Treatment and 
Control groups at the Primary Endpoint Assessment Visit 
3. Comparison of Percent Pain Relief between Treatment and Control 
groups reported by the Subject at the Primary Endpoint Assessment Visit 
4. Comparison of Subject Global Impression of Change at the Primary 
Endpoint Assessment Visit 
5. Comparison of number of Subjects with Resolution of Low Back Pain 
(remitters or cure, defined as a VAS score ≤ 2.5cm) at the Primary 
Endpoint Assessment Visit 
6. Evaluation of changes in primary and secondary efficacy metrics in 
Crossover Group following the Outcome Post Crossover Visit. 

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Supporting 
Analyses 
The Supporting Analyses will include: 
• 
Once data are complete, all primary and secondary outcome measures 
will be assessed at 12 months and compared to baseline within the 
Treatment group. The analysis will also explore correlation of outcomes 
to amount of stimulation delivered. 
• 
In the Crossover Group, outcome measures will be assessed at the 
Outcome Post Crossover Visit for all Subjects who met the inclusion 
criteria for low back pain at the Primary Endpoint Assessment Visit (i.e.: 
prior to Crossover) (Average Low Back Pain VAS of ≥6.0cm and ≤9.0cm 
on a VAS scale (0-10cm)) and inclusion criterion for ODI (Oswestry 
Disability Index score ≥21% and ≤60%). The analysis will also explore 
correlation of outcomes to amount of stimulation delivered. 
• 
Comparison of daily average VAS averaged over the prior 7 days of 
Journal entry with the single point VAS of recollection of prior 7 days of 
daily average pain. 
• 
Comparison of EQ-5D VAS between Treatment and Control groups at 
each visit at which EQ-5D is recorded through 12 months. 
• 
For both the Treatment and Control groups, a cumulative proportion of 
responder analysis51 for both ODI and reduction in back pain (VAS) so 
that the entire distribution of treatment response is depicted in a graph of 
the proportion of responders for all percentages from 0% to 100%. 
• 
Subject Global Impression of Change at 12 months. The analysis will also 
explore correlation of outcomes to amount of stimulation delivered. 
• 
Treatment Satisfaction Questionnaire at 12 months. The analysis will also 
explore correlation of outcomes to amount of stimulation delivered. 
• 
Clinical Global Impression – Global Improvement (clinician assessment) 
at 12 months. The analysis will also explore correlation of outcomes to 
amount of stimulation delivered. 
• 
Change in opioids used for treatment of low back pain from baseline to 12 
months. The analysis will also explore correlation of outcomes to amount 
of stimulation delivered. 
Additionally, ad hoc exploratory analyses may also be conducted.  
Note: Supporting analyses may be incomplete at the time of PMA 
submission. 
Primary Safety 
Assessment 
The primary safety assessment is serious device and/or procedure related 
adverse events in all Subjects in the Intent to Treat Cohort at the Primary 
Endpoint Assessment visit. 
Supporting 
Safety Analysis 
The PMA Submission will include 12 month safety data on all Subjects 
implanted with ReActiv8 including all Subjects implanted in the ReActiv8-B 
Trial for whom 12 month safety data are available, and other persons 
implanted with ReActiv8 in other clinical trials (including the ReActiv8-A 
PMCF Study) and all post-marketing registries that are registered on 
www.clinicaltrials.gov. 
A separate safety assessment will be performed on the Surgical Roll In 
group, including a poolability analysis. 

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Health 
Economics 
Cost-effectiveness of ReActiv8 therapy, extrapolated to the lifetime of the 
device, will be assessed. Key economic outcome measures to be recorded 
will include: 
• 
Change in work status at all visits. 
• 
Change in consumption of medications taken for low back pain at all visits 
compared to Baseline. 
• 
Assessment of health care utilization (office visits, hospital visits, 
emergency room visits, and other therapies such as physical therapy) at 
all visits. 
Note that the Health Economics assessment is likely to be incomplete at the 
time of PMA submission for ReActiv8, since not all Subjects will have 
reached the 12 month point at that time. 
Efficacy Follow 
Up 
All Subjects will be followed for efficacy until PMA approval unless the study 
is closed prior to PMA approval for any reason. 
Safety Follow 
Up 
All Subjects will be followed for safety until PMA approval or 7 years from the 
Baseline Visit, whichever is longer, unless the study is closed prior to PMA 
approval for any reason. 
Device Data 
At each follow up visit during which the ReActiv8 IPG will be interrogated, 
electrical parameters stored in the IPG such as lead impedance will be 
recorded. Results of threshold testing (if performed) and any reprograming 
will be recorded. 
Study Duration 
Anticipated to be ≤60 months from first Subject Baseline Visit to PMA 
submission. 
Informed consent for all Subjects will allow for continuing collection of safety 
and efficacy data for a total period of 7 years from the Baseline Visit. 
Study Schedule 
• 
Informed consent, baseline criteria verification,  
• 
ReActiv8 implant (1-45 days post inclusion) 
• 
Post-Implant Follow-up: 7 days -0/+10 days post-implant. 
• 
Randomization and Activation Visit: 14±3 days post-implant  
• 
14 day visit: 14 ± 7 days post-randomization 
• 
1.5 month visit: 45 ± 7 days post-randomization 
• 
2.5 month visit: 75 ± 10 days post-randomization 
• 
4 month visit: 120 -0/+20 days post-randomization - Primary Endpoint 
Assessment Visit 
• 
6 month visit: 180 ± 30 days post-randomization  
• 
8 month visit: 240 ± 30 days post-randomization 
• 
12 month visit: 360 -30/+ 60 days post-randomization 
• 
Annual follow up every 360 ± 60 days post-randomization until Study 
Closure 
For Subjects in the Control group, after the Subject completes the endpoint 
assessment at the Primary Endpoint Assessment Visit, the ReActiv8 will be 
programmed to deliver stimulation at a Subject-appropriate level, and other 
activities will be performed. 

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The study will be considered complete with regard to the primary endpoint 
after the required numbers of randomized Subjects have completed the 
Primary Endpoint Assessment Visit. 
Adjunctive 
Therapies 
• 
All medications for treatment of low back pain will be stabilized 30 days 
prior to the Baseline Visit and remain stabilized through the Primary 
Endpoint Assessment Visit. 
• 
All other treatments for low back pain (e.g. interventional pain treatments, 
chiropractic) will be prohibited until after the Primary Endpoint 
Assessment Visit. 
Eligibility 
Criteria 
Primary Inclusion Criteria 
1. Age ≥22 years, ≤75 years 
2. 7 day recall of average Low Back Pain VAS of ≥6.0cm and ≤9.0cm (on a 
10cm scale) at the Baseline Visit.  
3. Oswestry Disability Index score ≥21% and ≤60% at the Baseline Visit 
4. Chronic Low Back Pain defined as pain and discomfort localized below 
the costal margin and above the inferior gluteal fold (with or without 
referred leg pain) that has persisted >90 days prior to the Baseline Visit, 
which has resulted in pain in at least half of the days in the 12 months 
prior to the Baseline Visit, as reported by the Subject. 
5. Evidence of lumbar multifidus muscle dysfunction by the Prone Instability 
Test (PIT). 
6. Continuing low back pain despite >90 days of medical management 
including: 
a. At least one attempt of physical therapy treatment for low back pain, 
which may optionally be accomplished over multiple episodes or flare-
ups of low back pain. 
NOTE 1: Subjects who start a physical therapy program but are 
unable to complete it are still eligible with regards to this inclusion 
criterion. 
NOTE 2: Subjects who participated in a physical therapy program in 
the past since the onset of low back pain but are unwilling or 
unable to participate in a new physical therapy program are still 
eligible with regards to this inclusion criterion; 
b. For Subjects with medications prescribed and used for chronic low 
back pain, usage shall be at a stable dose in the 30 days prior to the 
Baseline Visit as reported by the Subject. 
NOTE 3: A stable dose means the Subject reports no significant 
change in regular use of medications, which may include PRN use, 
in the 30 days prior to the Baseline Visit. 
7. Be willing and capable of giving Informed Consent. 
8. Ability to comply with the instructions for use and to operate ReActiv8, 
and to comply with this Clinical Investigation Plan. 
9. Suitable for ReActiv8 surgery as determined by the implanting physician 
prior to inclusion. 
Primary Exclusion Criteria 
1. BMI > 35 

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2. Back Pain characteristics: 
a. Any surgical correction procedure for scoliosis at any time, or a current 
clinical diagnosis of moderate to severe scoliosis (Cobb angle ≥25°).52 
b. Lumbar spine stenosis, as defined by an anterior-posterior diameter of 
the spinal canal <10mm in Subjects with lower extremity pain. 
c. Neurological deficit possibly associated with the back pain (e.g. foot 
drop).  
d. Back pain due to pelvic or visceral reasons (e.g.: endometriosis or 
fibroids) or infection (e.g.: post herpetic neuralgia). 
e. Back pain due to inflammation or damage to the spinal cord or 
adjacent structures (e.g. arachnoiditis or syringomyelia). 
f. Pathology seen on MRI that is clearly identified and is likely the cause 
of the CLBP that is amenable to surgery.  
g. Back pain due to vascular causes such as aortic aneurysm and 
dissection. 
3. An independent assessment of any current indication for back surgery 
according to appropriate guidelines, or has indications for back surgery 
but cannot undergo surgery for other reasons. 
4. Leg pain described as being worse than back pain, or radiculopathy 
(neuropathic pain) below the knee. 
5. Source of pain is the sacroiliac joint as determined by the Investigator. 
6. Drug use per Subject report as follows: 
a. Current baseline use of >120mg oral morphine equivalent per day of 
opioids. 
b. Current use of breakthrough dose of >60mg oral morphine equivalent 
per day. 
c. Current requirement of opioids for treatment of a condition other than 
low back pain. 
d. History of any substance abuse at any time in the five years prior to 
the Baseline Visit. 
e. Currently taking >15mg Diazepam per day or equivalent.  
7. Surgical or other procedures exclusions: 
a. Any previous rhizotomy or rhizolysis procedure, including 
cryoablation, RF ablation or pulsed RF on the dorsal root ganglion 
(DRG) or the medial branch of the dorsal ramus nerve that crosses or 
lies below the T8 vertebra, within one year prior to the Baseline Visit. 
b. Anesthetic block of the DRG or medial branch of dorsal ramus nerve 
that crosses or lies below the T8 vertebra or injection of epidural 
steroids for back pain in the 30 days prior to the Baseline Visit. 
c. Any previous back surgery including laminectomy or discectomy at or 
below segmental level T8, or spinal fusion at any level. 
d. Any previous thoracic or lumbar sympathectomy. 
8. Any prior diagnosis of lumbar vertebral compression fracture, lumbar pars 
fracture, pars defect, or lumbar annular tear with disc protrusion that is 
amenable to surgery. 

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9. Planned surgery: 
a. Any major surgery (including elective surgery) planned in the twelve 
months following the Baseline Visit (does not include minor surgeries 
not expected to impact the lumbar spine (e.g. colonoscopy)). 
b. Any elective surgery of any kind (including, for example, tooth 
extraction, gynecological surgery or cosmetic surgery) in the time 
between the Baseline Visit and the Primary Endpoint Assessment 
Visit. 
10. Any co-morbid chronic pain conditions. 
11. Other clinical conditions: 
a. Pregnant or planning to be pregnant in the next 12 months, at the time 
of inclusion. 
b. Pregnancy at any time in the 6 months, or lactating at any time in the 
3 months, prior to the Baseline Visit. 
c. Any condition unrelated to the CLBP such as muscle wasting, muscle 
atrophy, other disability (e.g.: paraplegic, amputee, cerebral palsy) or 
muscular or skeletal disease (e.g.: arthritis in trunk or limbs, multiple 
sclerosis, rheumatoid arthritis) which, in the opinion of the Investigator, 
could limit physical movement or compliance with the protocol, or 
interfere with the assessment of efficacy of the investigational 
procedure.  
d. Poorly controlled diabetes (Type I or Type II) determined by HbA1c 
>8. 
e. Past or current neurological disorders (e.g.: known multiple sclerosis, 
motor neuron disease, Guillain-Barré syndrome, Parkinson’s, 
Huntington’s Disease, Alzheimer’s, epilepsy, stroke, brain cancer, 
traumatic brain injury). 
f. Cancer requiring treatment during the study. 
g. Any drugs (e.g.: immunosuppressive drugs) or co-morbidity that might 
inhibit wound healing or electrode scarring, or drugs associated with 
reduced effectiveness of neuromodulation for other applications. 
h. Any medical condition requiring anticoagulation (other than aspirin) 
that, in the opinion of the physician prescribing the anticoagulant, 
cannot be safely suspended for 5 days prior to device implantation 
surgery and an appropriate period after implantation surgery. 
i. 
Any active infection in the vicinity of the implant site or any systemic 
infection. 
12. Psycho-social exclusions 
a. Be involved in an injury claim under current litigation.  
b. Have a pending or approved financial compensation claim (e.g., 
worker’s compensation claim, long term disability claims) or any 
financial compensation (including social welfare payments) related to 
the Subject’s CLBP. 
c. Current incarceration (prison or jail) 
d. Have an assessment of current active depression significant enough 
(DASS depression score >953,54) to impact perception of pain, 

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compliance with intervention and/or ability to evaluate treatment 
outcome. 
e. Have evidence of an active disruptive psychological or psychiatric 
disorder or other known condition significant enough to impact 
perception of pain, compliance with intervention and/or ability to 
evaluate treatment outcome (e.g.: active depression, bipolar disease, 
Alzheimer’s disease) as determined by a psychologist or psychiatrist. 
13. Protocol Compliance Exclusions 
a. Inability or unwillingness to comply with all protocol requirements. 
b. Inability to maintain the prone or side lying position in a relaxed 
manner for the duration of each stimulation session. 
c. Inability to operate the Activator, such as arthritis that limits arm or 
shoulder movement, or inability to learn how to operate. 
d. Inability to assess changes in pain intensity or perform wound care. 
e. Inability or unwillingness to complete the Journal. 
14. General exclusions 
a. Any other active implantable device including an implantable device 
for back pain (such as an implantable drug pump or Spinal Cord 
Stimulator), pacemaker, implantable defibrillator, cochlear implant, 
deep brain stimulator, or other implanted neurostimulation device. 
b. Prior exposure to an implantable neurostimulator for treatment of pain, 
including spinal cord stimulation (including trial implant of SCS leads), 
occipital nerve stimulation or peripheral nerve stimulation. 
c. A condition currently requiring or likely to require use of MRI or 
diathermy while implanted with the ReActiv8. 
d. Therapy with any other investigational intervention (drugs, devices, or 
procedures) for the treatment of back pain at the time of the Baseline 
Visit, or at any time in the past if the past investigational intervention 
did not subsequently gain regulatory approval. 
e. Current or planned participation in any other clinical trial during 
participation in this Trial. 
f. Life expectancy <1 year. 

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3. 
The ReActiv8 Therapy 
3.1. Summary of ReActiv8 
The Mainstay ReActiv8 is an implantable electrical stimulation system that consists of an 
implantable pulse generator, leads, programmer, activator and magnet. Refer to the Investigator 
Brochure (IB) or the Implant and Programming Manual for more detail on device specifications 
and operation. 
Implantable Components of ReActiv8 
The ReActiv8 IPG, and the ReActiv8 leads (available in either 45 cm or 65 cm lengths), plus 
suture sleeves, are designed for permanent implant. The implantable components of ReActiv8 
are supplied sterile, and are intended for single use only. 
• 
Model 5100 ReActiv8 Implantable Pulse Generator (“IPG”) 
• 
Model 8000-45 ReActiv8 Percutaneous Stimulation Lead, 45 cm length (“lead”) 
• 
Model 8000-65 ReActiv8 Percutaneous Stimulation Lead, 65 cm length (“lead”) 
• 
Model 8145 ReActiv8 Percutaneous Stimulation Lead, 45 cm length (“lead”)  
• 
Model 8165 ReActiv8 Percutaneous Stimulation Lead, 65 cm length (“lead”) 
 
Note: The Model 8000-XX and Model 81XX leads are functionally equivalent. The Model 81XX 
leads incorporate a change to eliminate unused wires within the lead.  
 
Non-Implantable Components of ReActiv8 
The Torque Wrench and Stylet are provided to facilitate implantation of the IPG and leads. The 
Programmer is used to communicate with the IPG in order to program the IPG operational mode 
and settings, read history data from the IPG, and obtain IPG and lead status information. The 
Activator is used to initiate and/or suspend stimulation. The Magnet is used to enter Magnet 
Mode (with Magnet Mode operation determined by the programmed parameters of the IPG). 
• 
Model 6500/65X0 ReActiv8 Programmer System (“Programmer”) – All Model 65X0 
Programmers contain a Lenovo E420 Laptop computer. Model 6500 contains a 
“universal” set of power cords (for the UK, US, Belgium and Australia), while Model 65X0 
contains one power cord that varies by the intended geography for use (e.g., Model 
6530 contains a US power cord only). Mainstay provides the following components of 
the Model 6500/65X0) Programmer in case replacements are needed: 
o Model 6600 Lenovo E420 Laptop (“E420 Laptop”) 
o Model 6700 Medical Grade AC Adapter for the Model 6500/65X0 Programmer  
o Model 6800 Battery for the Model 6600 Lenovo E420 Laptop  
o Model 6000 ReActiv8 Programmer Wand (“Wand”) 
o Model PP00 Universal Replacement Power Cord Package with AUS, UK, USA 
and Belgian Power Cord 
o Model PP30 USA Replacement Power Cord Package  
• 
Model 7500/75X0 ReActiv8 Programmer System (“Programmer”) – All Model 75X0 
Programmers contain a Lenovo E440 laptop computer. Model 7500 contains a 
“universal” set of power cords (for the UK, US, Belgium and Australia), while Model 
75X0 contains one power cord that varies by the intended geography for use (e.g., 
Model 7530 contains a US power cord only). Additionally, the Model 7500/75X0 
Programmer contains the Model 6750 Medical Grade AC Adapter and the Model 6000 

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Programmer Wand (unchanged from the Model 6500/65X0). Mainstay provides the 
following components of the Model 7500/75X0) Programmer in case replacements are 
needed: 
o Model 7600 Lenovo E440 Laptop (“E440 Laptop”) 
o Model 6750 Medical Grade AC Adapter for the Model 7500/75X0 Programmer 
o Model 7800 Battery for the Model 7600 Lenovo E420 Laptop 
o Model 6000 ReActiv8 Programmer Wand (“Wand”) 
o Model PP00 Universal Replacement Power Cord Package with AUS, UK, USA 
and Belgian Power Cord 
o Model PP30 USA Replacement Power Cord Package  
• 
Model 7000 ReActiv8 Activator (“Activator”) 
• 
Model 4000 ReActiv8 Magnet (“Magnet”) 
• 
Model 5500 ReActiv8 Torque Wrench – single use - (“Torque Wrench”) 
 Accessories Included with the ReActiv8 
Mainstay supplied accessories included with the ReActiv8 are: 
• 
Torque Wrench (supplied in the IPG package and also available as a standalone 
accessory) 
• 
Suture sleeve (optional - supplied in the Lead package) 
• 
Lead Stylet (supplied in the Lead package) 
• 
Model TUN1 Mainstay Tunneler 
 Other Accessories  
The Lead is designed to be placed using a commercially available 7 Fr Introducer Kit (not 
included with ReActiv8) and the Mainstay Model TUN1 Tunneler (included with ReActiv8) or 
commercially available equivalent. 
The ReActiv8 delivers stimulation via electrodes placed adjacent to the medial branch of the 
dorsal ramus nerve at the preferred location as it crosses the L3 transverse process. The 
electrodes are located at the distal end of a Stimulation Lead that is connected to an 
implantable pulse generator (IPG) placed in a surgical pocket typically above the buttocks (in a 
place similar to that used in Spinal Cord Stimulation implants). Two leads are placed (one each 
left and right side) and connected to the IPG. The IPG is externally programmable with a 
Programmer. Stimulation is manually initiated by an external device (Activator) and can be 
stopped with the Activator or Magnet. 
The leads incorporate a fixation mechanism that consists of two sets of 3 point tines – one 
facing forward and one facing backwards. The tines are positioned to lie on either side of the 
intertransversarii lateralis, thus reducing the risk of lead dislodgement by either advancement or 
retraction. The lead body is a polyurethane tube containing spiral wound multi-filar wires and 
incorporates a lumen to allow passage of a stylet.  
3.2. Surgical Implantation and Device Activation 
Surgical implantation is adapted from familiar techniques used for medial branch rhizotomy and 
spinal cord stimulation. Details of the recommended surgical procedure, device programming 
and use by the Subject are to be found in the Implant and Programming Manual and the User 
Manual. 
In normal use, following implantation and a suitable recovery period, the IPG is programmed to 
deliver stimulation that elicits smooth contraction of the lumbar multifidus. Typical parameters 

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are 0.5 mA, 200 μs, 20 Hz, with 10 seconds of stimulation followed by 20 seconds of no 
stimulation, delivered for a Session of 30 minutes. Refer to the Implant and Programming 
Manual for device programming. 
To start a Session, the Subject is positioned comfortably prone or lying on the side. The Subject 
initiates delivery of electrical stimulation with the Activator, which can also be used to stop 
stimulation (e.g.: in case of interruption). Two sessions of stimulation, each of 30 minutes, are 
delivered each day (e.g. morning and evening). 
3.3. Physician Training 
All physicians who will implant any portion of the ReActiv8 in the clinical Trial will participate in 
product training as outlined in the Training Strategy. A “Certificate of Completion” will be issued 
to each implanting physician who completes the training to the satisfaction of the trainer. 
All physicians and other health care personnel who will interact with the programmer (e.g.: non-
implanting physicians) will receive training from the Sponsor, which includes lectures and use of 
a programmer with a simulator (e.g.: a ReActiv8 IPG connected to a dummy load). This training 
will also include interaction with the external components handled by the Subject, including the 
Activator and Magnet. 

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4. 
Study Design 
International, multi-center, prospective, randomized, sham controlled, blinded Trial with an 
adaptive statistical design. 
4.1. Hypothesis 
In Subjects with chronic low back pain and no prior surgery and with unsatisfactory pain relief 
despite medical management (including at least physical therapy and medications), episodic 
electrical stimulation of the medial branch of the dorsal ramus nerves to cause contraction of the 
lumbar multifidus muscles can lead to relief of low back pain and the disabling effects of back 
pain. 
4.2. Proposed Indications for Use for ReActiv8 
ReActiv8 is an adjunct to medical management in adults with Chronic Low Back Pain for 
relief of pain in subjects who have failed at least medical management and physical 
therapy. 
4.3. Study Population 
Subjects with chronic low back pain that impacts their daily living, who satisfy the following 
general criteria: 
1 
Chronic low back pain and disability despite medical management, including at least 
one attempt of physical therapy treatment for low back pain (which may optionally be 
accomplished over multiple episodes or flare-ups of low back pain), and may be 
using prescribed pain relieving drugs (including muscle relaxants) which have been 
at a stable appropriate dose for a minimum of 30 days. 
2 
No contraindications for enrollment. 
Detailed Inclusion and Exclusion criteria are listed in Section 5. 
4.4. Study Size and Duration 
A minimum of 116 evaluable Subjects is required to sufficiently power the primary endpoint. To 
allow for attrition, 128 Subjects will be randomized as part of the Intent to Treat Cohort. Up to 80 
additional Subjects will be randomized as part of the Surgical Roll In phase as described below 
(assuming one implanting surgeon per site). Therefore, the total number of implanted and 
randomized Subjects will be up to 208. In order to account for screen failures prior to implant up 
to 800 Subjects will be enrolled. An adaptive statistical design using a single interim look will be 
used for sample size re-estimation. 
4.4.1. 
Investigational Sites 
Investigators may include a number of different specialties including Physical Medicine and 
Rehabilitation (PM&R), Interventional Pain, Neurosurgery, Neurology and Spine Surgeons. The 
key investigational activities include Subject recruitment, device implant, and Subject follow up 
(including device management and Trial data collection). Some investigators will perform all of 
these activities, and some may not. For example, some PM&R physicians will not perform 

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surgery, and the surgery will be performed by a Sub-investigator (e.g.: a neurosurgeon) who 
may be at a different site. The Trial design accommodates this situation. 
There will be up to 40 investigational sites with a Principal Investigator who may or may not be 
the implanting physician. One or more Sub-investigators per site (or affiliated site if the affiliated 
site has a different Ethics Committee or IRB) may be used for example for device implantation 
and Subject recruitment. 
4.4.2. 
Surgical Roll In Phase 
Following training, up to the first two Subjects implanted by the same implanting physician may 
be prospectively included in a Surgical Roll In group and not included in the Intention To Treat 
Cohort. The Surgical Roll In phase for each implanting physician will be deemed complete upon 
consultation with the implanting physician and the Sponsor. In some cases, there will be no 
Surgical Roll In phase, for example if the implanting physician participated in the ReActiv8-A 
Trial. Note that Subjects included in the Surgical Roll In Phase who are not successfully 
implanted are not included in the Surgical Roll In group. 
All Subjects implanted in the Surgical Roll In group will be randomized to either Treatment or 
Control, and follow the identical visit schedule as Subjects included after the Surgical Roll In 
phase. With approximately 40 implanting physicians and up to 2 Subjects in the Surgical Roll In 
phase per implanting physician, up to 80 Subjects may be included in the Surgical Roll In group.  
4.4.3. 
Study Duration 
Total study duration is anticipated to be ≤60 months from first Subject Baseline Visit through 
PMA submission. 
Informed consent for all Subjects will allow for continuing data collection for a total period of 7 
years from Baseline Visit. 
4.5. Assessment of Lumbar Multifidus Dysfunction 
The Prone Instability Test (PIT) has been utilized in variety of studies55 and is used in this Trial 
to identify Subjects likely to have multifidus dysfunction. The PIT was designed to identify 
Subjects who would likely respond to a lumbar stabilization exercise program, and in many of 
these Subjects spine instability is thought to be due to LM dysfunction consequent to 
compromised neural drive to the LM. It has established reliability (K = 0.87).56 It was one of 4 
variables shown to be predictive of success with a stabilization exercise program for Subjects 
with low back pain that included exercises designed to reactivate the LM.57 Additionally, the 
same study demonstrated that those Subjects who had a positive PIT also had reduced LM 
thickness change when compared to Subjects who had a negative PIT. The PIT may be the 
only predictive test that has demonstrated reasonable inter-tester reliability.58 
The PIT will be performed by appropriately qualified individuals (e.g.: physical therapist, 
Physical Medicine and Rehabilitation Physician, Orthopedic Surgeon). Each person performing 
the PIT shall undergo training as follows: 
• 
The training materials shall be standardized across sites. 
• 
The person conducting the training shall be a reputable and appropriately qualified 
individual with experience in training on the PIT (e.g.: a physical therapist or physical 
medicine physician who regularly conducts training of other specialists). 

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• 
A formal training plan shall be developed in conjunction with the trainer(s), including 
“hands on” conduct of the PIT. 
• 
Each trainee will be assessed by the trainer, including a “hands-on” demonstration of 
competence in performing the PIT to validate the training. 
• 
Upon successful completion of the training and assessment, the trainer shall sign a 
“Certificate of Training” for the trainee to document that the trainee is qualified to conduct 
the PIT for this Trial. 
In summary, to conduct the PIT, the Subject is positioned prone on an examination table. The 
test is conducted in two stages: 
Stage 1:  Tester performs Posterior-Anterior (P-A) glides over each lumbar segment for pain 
provocation and identifies the painful segments. 
Stage 2: Repeat P-A with hips extended (Feet just off of the floor) as shown in Figure 1. 
A Positive Test is when any previously painful segments become pain-free. The level of 
instability will be documented.  
 
Figure 1: Conducting the Prone Instability Test 
4.6. Outcome Measures 
Several outcome measures are used to assess the primary and secondary endpoints of the 
Trial. 
4.6.1. 
Low Back Pain Visual Analog Scale (VAS) 
The primary outcome measure is pain, a Patient Reported Outcome (PRO). The instrument 
used for evaluating pain is the continuous Visual Analog Scale comprised of a horizontal line 
10cm in length, anchored by 2 verbal descriptors, one for each symptom extreme for Low Back 
Pain, as recommended by IMMPACT.44  

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Subjects will be advised to place a line on the VAS that represents their average low back pain 
for the last 7 days. The scale is anchored with “no pain” on the left side of the scale to “worst 
imaginable pain” on the right side of the scale.  
Note: 
This is a study on low back pain. Thus the Subject will be presented a VAS that is 
specific to the low back pain that led to being enrolled in this study. This allows 
separation of the low back pain symptoms from other pain causing events (e.g.: 
toothache) which could confuse interpretation of the results. People with low back pain 
often also report leg pain, which should be distinguished from the low back pain that led 
to enrollment in the Trial. 
The VAS for low back pain is recorded by the Subject at each of the visits and is used for the 
primary outcome.  
A daily Journal will also be collected for 7 days prior to each visit through the 120 day follow-up, 
completed preferably at the same time of day (e.g.: between 5PM and 8PM). 
4.6.2. 
ODI 
Oswestry Disability Index (ODI) is a disease specific assessment of the disabling effects of back 
pain.48 The ODI covers 1 item on pain and 9 items on activities of daily living (personal care, 
lifting, walking, sitting, standing, sleeping, sex life, social life, and traveling). ODI is reported as a 
score from 0 to 100%. 
The relevance of changes in ODI has been explored by many authors, and discussions abound 
on Minimal Clinical Important Difference (MCID), Minimally Important Change (MIC) and the 
like. It is important to distinguish between significance of change scores for studies on acute low 
back pain where the natural history of improvement would suggest reversion to the mean, and 
studies on chronic low back pain where the likelihood of improvement is low. Hägg et al59 
suggested that an absolute change of 10 (in the 100 point ODI scale) is the MCID and Ostelo60 
concurs that a Minimally Important Change is 10.  
4.6.3. 
EQ-5D 
EQ-5D is the acronym for the European Quality of Life Score on Five Dimensions. There are 
many instruments used for assessment of Quality of Life,61 and EQ-5D appears to be the most 
commonly used in studies of therapies for back pain, and is often used for cost utility 
assessment.62 The EQ-5D descriptive system comprises the following 5 dimensions: mobility, 
self-care, usual activities, pain/discomfort and anxiety/depression. The original EQ-5D used a 3 
level reporting system (no problems, some problems, extreme problems), and more recently a 
five level reporting system has been developed and validated (no problems, slight problems, 
moderate problems, severe problems, and extreme problems), referred to as the EQ-5D-5L, 
which has been tested and validated.63,64 This Clinical Investigation uses the EQ-5D-5L, referred 
to in its short form as EQ-5D. 
The EQ-5D is designed for use primarily as a self-reported measure (i.e.: the questionnaire is 
completed by the Subject alone), and therefore lends itself to clinical trials in which the outcome 
assessment is to be blinded. Population norms for EQ-5D for various populations have been 
reported, and categorized by age, gender and social class. EQ-5D is reported as an index up to 
1.00 (note: EQ-5D index scores of <0 are possible in some circumstances). 

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4.6.4. 
Percent Pain Relief (PPR) 
Percent Pain Relief (PPR) is a question asked to the Subject by the Investigator or Coordinator 
in which the Subject is asked to report the percent pain relief at the time of the current visit 
compared to the pain at baseline. 
4.6.5. 
SGIC 
Subject Global Impression of Change (SGIC) is based on the “Patient Global Impression of 
Change” as described by Farrar.65 The Subject is presented with a questionnaire with 7 choices, 
as shown in Figure 2. 
Since I enrolled in the study, my overall status is 
1. □ Very much improved 
2. □ Much improved 
3. □ Minimally improved 
4. □ No change 
5. □ Minimally worse 
6. □ Much worse 
7. □ Very much worse 
Figure 2: Subject Global Impression of Change (SGIC) Questionnaire 
4.6.6. 
Clinical Global Impression 
Clinical Global Impression – Global Improvement consists of the questions that are to be 
completed by the Investigator as shown in Figure 3. 
In your opinion as a clinician, compared to the Subject’s 
situation at baseline, would you say the Subject is: 
□ Much better 
□ Slightly better 
□ About the same 
□ Slightly worse 
□ Much Worse 
Figure 3: Clinical Global Impression Questionnaire 
4.6.7. 
Resolution of Back Pain 
Resolution of back pain (cure) is defined as a Subject with 7 day average low back pain VAS 
≤2.5cm on the 10cm VAS. 

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4.7. Clinical Trial Endpoints 
A single primary endpoint will be analyzed. Multiple secondary endpoints and exploratory 
endpoints will be analyzed. 
4.7.1. 
Primary Endpoint – Low Back Pain VAS 
The Primary Efficacy Endpoint is a comparison of responder rates between Treatment and 
Control groups, where a “responder” is a Subject with ≥30% reduction from baseline in average 
low back pain VAS without any increase from baseline in pain medication and/or muscle 
relaxants prescribed and taken in the two weeks prior to the Primary Endpoint Assessment Visit. 
Note: The primary outcome measure is intended to assess the efficacy of 120 days of 
stimulation. Thus the visit for assessment of the primary outcome must occur no sooner 
than 120 days post randomization. 
Records of pain medications will be collected along with all other medications used for treatment 
of low back pain, which are also being collected for analysis of secondary and cost-
effectiveness endpoints. The Subject will report medications taken at each scheduled follow-up 
visit. Rescue medications taken on an exceptional basis for acute pain conditions other than 
back pain will also be documented and their possible effect examined as part of sensitivity 
analyses. 
After the Primary Endpoint Assessment Visit, Subjects will be permitted to adjust their drug use 
as appropriate, based on consultation with their physicians, and data on drugs prescribed and 
taken will continue to be collected. 
4.7.1.1. Hypotheses 
The primary efficacy objective will be assessed by the following hypotheses:  
H0: ΠVAST = ΠVASC 
HA: ΠVAST ≠ ΠVASC, 
where ΠVAST is the proportion of Subjects meeting primary success criteria in the Treatment 
group and ΠVASC is the proportion of subjects meeting success criteria in the Control group. 
The hypotheses will be tested using a two-sided binomial test for a difference in proportions. 
The objective will be met if a statistically significant difference favoring the Treatment group is 
found. 
The study will be considered a success if the primary efficacy objective is met. 
4.7.1.2. Sample Size Rationale 
The sample size for the study is determined under the following assumptions for the primary 
efficacy endpoint: 
• 
Minimum power of 80% 
• 
Type I error of 5% 
• 
Assumed primary efficacy success in Treatment group: 50% 
• 
Assumed primary efficacy success in Control group: 25% 
Under the above assumptions, a minimum of 116 evaluable Subjects is required in order to 
demonstrate superiority of the ReActiv8 treatment. The total sample size is increased by 10% to 
128 to allow for attrition. 

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An adaptive statistical design using a single interim look will be used for sample size re-
estimation when at least 50% of the implanted Subjects have completed the Primary Endpoint 
Assessment Visit. Details of the interim analysis are provided in the Statistical Analysis Plan.  
4.7.2. 
Secondary Efficacy Endpoints 
All tests of significance will be tested utilizing an overall Type I error of 5%. The overall Type I 
error will be maintained by utilizing Hochberg’s method to test the collection of the first five 
secondary objectives. These will be tested only if the primary efficacy endpoint is met.  
1. Comparison of change from baseline in Oswestry Disability Index (ODI) between Treatment 
and Control groups at the Primary Endpoint Assessment Visit. 
2. Comparison of change from baseline in EQ-5D between Treatment and Control groups at 
the Primary Endpoint Assessment Visit 
3. Comparison of Percent Pain Relief between Treatment and Control groups reported by the 
Subject at the Primary Endpoint Assessment Visit 
4. Comparison of Subject Global Impression of Change at the Primary Endpoint Assessment 
Visit 
5. Comparison of number of Subjects with Resolution of Low Back Pain (remitters or cure, 
defined as a VAS score ≤ 2.5cm) at the Primary Endpoint Assessment Visit 
6. Evaluation of changes in primary and secondary efficacy metrics in the Crossover Group (as 
defined in Section 4.10) following the Outcome Post Crossover Visit. 
4.7.2.1. Hypotheses 
ODI 
The ODI efficacy objective will be tested under the following hypotheses: 
H0: µODIT = µODIC 
HA: µODIT ≠ µODIC 
Where µODIT is the mean change in ODI in the Treatment group and µODIC is the mean change 
in ODI in the Control group at the Primary Endpoint Assessment Visit. The hypotheses will be 
tested using a two-sided two-sample t-test for a difference in mean changes. 
In addition, a cumulative proportion of responder analysis of ODI will be performed.51 
EQ-5D 
The EQ-5D efficacy objective will be tested under the following hypotheses: 
H0: µEQ5DT = µEQ5DC 
HA: µEQ5DT ≠ µEQ5DC 
Where µEQ5DT is the mean change in EQ-5D (index score) in the Treatment group and 
µEQ5DC is the mean change in EQ-5D in the Control group from baseline to the Primary 
Endpoint Assessment Visit. The hypotheses will be tested using a two-sided two-sample t-test 
for a difference in mean changes.  
Percent Pain Relief 
The secondary Percent Pain Relief efficacy objective will be tested under the following 
hypotheses 
H0: µPPRT = µPPRC 
HA: µPPRT ≠ µPPRC 

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Where µPPRT is the mean percent pain relief in the Treatment group and µPPRC is the mean 
percent pain relief in the Control group at the Primary Endpoint Assessment Visit. The 
hypotheses will be tested using a two-sided two-sample t-test for a difference in mean changes. 
Subject Global Impression of Change 
The secondary Subject Global Impression of Change efficacy objective will be tested under the 
following hypotheses 
H0: DISTRIBUTIONSGICT = DISTRIBUTIONSGICC 
HA: DISTRIBUTIONSGICT ≠ DISTRIBUTIONSGICC 
Where DISTRIBUTIONSGICT is the distribution of the Global Impression of Change in the Treatment 
group and DISTRIBUTIONSGICC is the distribution of Global Impression of Change in the Control 
group at the Primary Endpoint Assessment Visit. The hypotheses will be tested using a two-
sided Mann-Whitney test. 
Resolution of Low Back Pain 
The secondary Resolution efficacy objective will be tested under the following hypotheses: 
H0: ΠRLBPT = ΠRLBPC 
HA: ΠRLBPT ≠ ΠRLBPC 
Where ΠRLBPT is the proportion of Subjects with a VAS back pain assessment for the previous 
7 day of VAS ≤2.5cm (on a 10cm scale) in the Treatment group and ΠRLBPC is the proportion 
of Subjects with a VAS back pain assessment for the previous 7 day average VAS ≤2.5cm in 
the Control group at the Primary Endpoint Assessment Visit. The hypotheses will be tested 
using a two-sided binomial test for a difference in proportions. 
4.7.3. 
Primary Safety Assessment 
The primary safety assessment is of serious device and/or procedure related adverse events in 
all Subjects in the Intent to Treat Cohort at the Primary Endpoint Assessment Visit. All reported 
adverse events will be documented and reported with summary statistics presented for 
observed rates. There are no formal, statistical hypotheses being tested in the safety 
assessment. 
4.7.4. 
Supporting Safety Analysis 
The PMA Submission will include 12 month safety data on all Subjects implanted with ReActiv8 
including all Subjects implanted in the ReActiv8-B Trial for whom 12 month safety data are 
available, and other persons implanted with ReActiv8 in other clinical trials (including the 
ReActiv8-A PMCF Study) and all post-marketing registries that are registered on 
www.clinicaltrials.gov. This data will be provided as a separate analysis of the safety on all 
implanted persons as an appendix to the ReActiv8-B Trial results. 
A separate safety assessment will be performed on the Surgical Roll In Cohort, including a 
poolability analysis. 
4.7.5. 
Supporting Analyses 
The supporting efficacy analyses will include: 
• 
Once data are complete, all primary and secondary outcome measures will be assessed at 
12 months and compared to baseline within the Treatment group. The analysis will also 
explore correlation of outcomes to amount of stimulation delivered. 

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Note: For all supporting analyses, amount of stimulation delivered will be defined as the 
number of minutes stimulation was delivered divided by the number of minutes that 
stimulation could have been delivered. 
• 
In the Crossover Group, outcome measures will be assessed at the Outcome Post 
Crossover Visit for all Subjects who met the inclusion criteria for low back pain at the 
Primary Endpoint Assessment Visit (i.e.: prior to Crossover) (Prior week average Low Back 
Pain, VAS of ≥6.0 cm and ≤9.0 cm on a 10 cm VAS scale) and inclusion criterion for ODI 
(Oswestry Disability Index score ≥21% and ≤60%). The analysis will also explore correlation 
of outcomes to amount of stimulation delivered. 
• 
Comparison of daily average VAS averaged over the prior 7 days of Journal entry with the 
single point VAS of recollection of prior 7 days of average pain. 
• 
Comparison of EQ-5D VAS between Treatment and Control groups at each visit at which 
EQ-5D is recorded through 12 months. 
• 
For both the Treatment and Control groups, a cumulative proportion of responder analysis, 
so that the entire distribution of treatment response is depicted in a graph of the proportion 
of responders for all percentages of low back pain VAS reduction from 0% to 100%. In this 
manner, the number of Subjects with ≥50% low back pain VAS improvement can be 
determined, for example.  
• 
Subject Global Impression of Change at 12 months. The analysis will also explore 
correlation of outcomes to amount of stimulation delivered. 
• 
Treatment Satisfaction Questionnaire at 12 months. The analysis will also explore 
correlation of outcomes to amount of stimulation delivered. 
• 
Clinical Global Impression – Global Improvement (clinician assessment) at 12 months. The 
analysis will also explore correlation of outcomes to amount of stimulation delivered. 
• 
Change in opioids used for treatment of low back pain from baseline to 12 months. The 
analysis will also explore correlation of outcomes to amount of stimulation delivered. 
Additional, ad hoc exploratory analyses may also be conducted.  
Note that the supporting analyses may be incomplete at the time of PMA submission since not 
all Subjects may have reached 12 months post-randomization. 
4.7.6. 
Health Economics 
Cost-effectiveness of ReActiv8 therapy, extrapolated to the lifetime of the device, will be 
measured. Key economic outcome measures to be recorded will be: 
• 
Change in work status at all visits. 
• 
Change in consumption of medications taken for low back pain at all visits compared to 
Baseline. Note that an analysis may be performed of different categories of medications 
including for example opioids, muscle relaxants and anti-depressants. 
• 
Assessment of health care utilization (office visits, hospital visits, emergency room visits, 
and other therapies such as physical therapy) at all visits past the endpoint visit. 
Note that both the Treatment and Control group Subjects are required to keep medications 
constant from randomization until the Primary Endpoint Assessment Visit, and other health care 
utilization will be as per the protocol (e.g.: no additional therapies, see Section 5.3). Experience 
in the ReActiv8-A Clinical Trial has shown that some subjects who experience relief from low 
back pain may reduce their pain medications (despite instructions to keep medications 
constant), and some subjects may increase medications (thereby classifying them as non-
responders). All changes in medications will be recorded. 

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Following the Primary Endpoint Assessment Visit, all Subjects will be permitted to adjust 
medications and to use other health care resources. For the Crossover Group, this may yield 
some information on how Subjects will adjust medications during the treatment phase. 
Note that completion of the Health Economics assessments is likely to be incomplete at the time 
of PMA submission for ReActiv8, since not all Subjects will have reached the 12 month point at 
that time. 
4.8. Control Arm 
The intent of eliciting multifidus contraction is to retrain the motor control system and reactivate 
the multifidus for improved spine stability. Based on data from the Feasibility Study and the data 
available to date in the ReActiv8-A Trial, there is no straightforward dose response (i.e.: there is 
a spectrum of responses to the same dose), and the time to measurable response is different 
between Subjects. Furthermore, there is no known “sub-threshold” stimulation which is 
indistinguishable to the Subject from “therapeutic stimulation”, and therefore a perfect sham is 
not possible.  
The Control Arm for this Trial is Subjects implanted with ReActiv8, and the output programmed 
to deliver a minimum level of electrical stimulation. This is a sham in the sense that all Subjects 
receive some level of electrical stimulation, and Subjects in the Control Arm may experience 
sensations as a result of the stimulation.  
In particular, Control Arm Subjects will be subject to the following stimulation: 
• 
Three stimulation pulses of 0.1mA and 31µs duration delivered between the IPG can 
(-ve) and the most proximal electrode (+ve) on the lead ipsilateral to the location of the 
IPG delivered every two minutes during a stimulation session. 
• 
Electrical pulses (4 pulses of 31µs, 0.4mA) to assess electrode impedance of the 
programmed electrode at the start of every stimulation session. 
The risk of bias is addressed by the following: 
• 
All randomized Subjects will have implant surgery. Thus any possible placebo effect due 
to surgical intervention will be the same in both arms. 
• 
All Subjects with have the same follow up schedule until the endpoint assessment. Thus 
any response due to the Hawthorne effect66 will be the same in both arms. 
• 
All Subjects will be instructed to have the same device interactions (lie down, press 
“start” and get up after 40 minutes – 30 minutes stimulation and ten minutes’ rest). Thus 
any placebo response due to the device interactions or simply lying down and relaxing 
for 80 minutes per day will be the same in both arms. 
• 
All Subjects will experience interactions with the programmer at the follow up visits. In 
particular, all Subjects will have battery state, lead impedance and compliance data read 
out from the IPG. 
• 
Subjects in both arms may or may not experience sensations associated with the 
stimulation. It is likely that Subjects in the Treatment group will perceive muscle 
contraction. It is possible that Subjects in the Control group will experience a brief 
muscle twitch every two minutes, and possibly one or more muscle twitches at the start 
of each session in response to the electrical impedance testing pulses. 
• 
The proposed primary endpoint is binary (e.g., success or failure), and thus the Subject 
needs to reach a substantial level of pain reduction in order to be counted as a success. 
This makes it less likely that a placebo effect will bias the study results. 
 

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4.9. Blinding and Blinding Assessment 
The following persons will be blinded to Subject allocation to Treatment or Control Arm: 
1. Subjects 
2. Investigators (but may become unblinded as a result of managing any AEs) 
3. Other healthcare providers (e.g.: primary care physicians) 
4. Members of the Adjudication Committees 
Subjects will not be informed of allocation to Treatment or Control at any time prior to the 
Primary Endpoint Assessment Visit. Subjects in the Crossover Group will feel LM contractions 
with stimulation, and are likely become unblinded following crossover. There will not be a 
Blinding Assessment at any time after the Primary Endpoint Assessment Visit. 
Measures taken to improve the likelihood of maintaining blinding of Subjects include: 
• 
Careful wording in the Informed Consent – e.g.: “you may or may not feel a sensation during 
participation in this Trial. The effect of the treatment may not be achieved until sometime 
after initiation of treatment as every person reacts differently to treatment. Nevertheless, the 
treatment may be providing an effect, and therefore it is important that you continue to follow 
instructions at every daily treatment session.” 
• 
Subjects will be advised to not tell anyone of the sensations they experience,b or the 
treatment they received, including other Subjects, Investigators, outcome assessors, and 
Sponsor personnel. 
• 
Subjects will be advised in the informed consent that the output parameters of the ReActiv8 
IPG may be adjusted up or down at any time in a follow up visit. 
• 
Use of carefully scripted Subject interaction with Investigators, coordinators and Sponsor 
personnel at each follow up visit. 
• 
Investigators will be blinded as to randomization assignment of Subjects at all times until 
primary endpoint data are available (unless managing an AE requires unblinding of the 
Subject’s randomization assignment). 
• 
Persons performing interview based Subject assessments will be blinded as to Subject 
allocation. 
• 
All members of the adjudication committee will be blinded as to Subject allocation. 
• 
Subjects will be instructed to not compare notes with other Subjects in the Trial, and in 
particular to not use the internet to share experiences with other Subjects, as doing so a 
seriously prejudice the results of the Trial. 
• 
During the clinical Trial prior to the primary outcome assessment, public information 
available from the Sponsor (e.g.: the web site) will be carefully worded with regard to 
sensations perceived with stimulation from the ReActiv8. 
The primary outcome measure is average low back pain VAS completed alone by the Subject at 
the visits without assistance. Thus the endpoint assessment is inherently blinded since no 
assessor is involved. 
After endpoint data collection at the Primary Endpoint Assessment Visit, all Subjects will 
complete a questionnaire to assess blinding. It is anticipated that the Treatment group will be 
 
b  
Subjects will be advised that if they experience pain, discomfort, or any untoward effect, then they should contact the site 
research coordinator and not discuss with anyone else. 

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found to be predominantly unblinded because they will have felt muscle contraction and it is 
expected that those Subjects whose back pain has improved will assume they are in the 
Treatment group. It is anticipated that the Control group will be approximately 50% unblinded. 
The blinding assessment questionnaire for Subjects is shown in Figure 4, and based on the 
methods suggested by Bang.67 
Do you think you were in the Treatment or Control group? 
 
□ Treatment 
□ Control 
□ No idea 
How certain are you of your answer? 
 
□ Strongly believe 
□ Somewhat believe  
□ No idea 
Figure 4: Blinding Assessment Questionnaire 
The Subject may experience an adverse event that requires the Investigator to be made aware 
of the Subject’s randomization assignment. Unblinding should only occur in circumstances 
where there is a risk to Subject health or safety and every attempt should be made to contact 
the Sponsor before unblinding the Subject’s randomization assignment. In addition, every 
attempt should be made to keep the Subject blinded to the randomization assignment, unless 
the Investigator believes that the Subject should be made aware in order to manage the 
adverse event. If it is necessary to unblind the Subject’s randomization assignment, 
documentation of this will be provided through a study deviation case report form.  
4.10. Crossover 
The clinical effect is not reversible since removal of stimulation from a Subject who already has 
restored motor control is unlikely to result in return of the back pain or disability. Thus neither a 
double crossover nor a randomized withdrawal is possible. However, a single crossover is 
possible. 
After collection of all endpoint data at the Primary Endpoint Assessment Visit, all Subjects in the 
Control group will have the ReActiv8 IPG programmed to deliver Subject appropriate stimulation 
to cause strong smooth contraction of the multifidus. 
4.11. Data Collection 
To avoid introduction of bias, all Subject reported endpoint data at Subject contact visits will be 
collected before any other intervention or interview during the Subject follow up. The data 
collection session shall not be attended by people not necessary for the data collection (e.g.: 
Investigator, the Subject’s relatives or friends, or Sponsor personnel). 
Programming the ReActiv8 and data collection via the Physician Programmer will be performed 
by the Investigator or delegate, with the assistance (if requested) of personnel from the Sponsor 
or CRO under Investigator direction and guidance. 
4.12. Stimulation Compliance 
Subjects will be required to deliver stimulation for 60 minutes per day up to the Primary 
Endpoint Assessment Visit, typically in two Sessions of 30 minutes each. The IPG contains data 
logging of the times for start and stop of each stimulation Session, and the data will be collected 
and recorded at each follow up visit.  

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Note: ReActiv8 does not allow stimulation greater than the maximum programmed number of 
minutes in any day (midnight to midnight), which is set at 60 by default. 
Note:  A Session can be prematurely stopped with the Magnet or the Activator, and stimulation 
can be restarted to complete the Session later in the day. 
Following the Primary Endpoint Assessment Visit, Subjects in the Treatment group will be 
advised to continue to deliver stimulation for 60 minutes per day (in two 30 minute Sessions), 
but will be permitted to reduce the amount of stimulation as desired. 
Subjects in the Crossover Group will be advised to continue to deliver stimulation for 60 minutes 
per day up to the Outcome Post Crossover Visit. Thereafter, Subjects will be advised to 
continue to deliver stimulation in two 30 minute sessions per day but will be permitted to reduce 
the amount of stimulation as desired.  
Subjects should be encouraged to contact site personnel if they find that they are unable to 
complete a Session for any reason. 
For the purposes of analyses, “stimulation compliance” will be defined as the amount of time 
spent delivering stimulation compared to the amount of time that stimulation could have been 
delivered in any period, expressed as a percentage. For the purposes of this analysis, “session 
compliance” will be defined as the number of Sessions during which 100% of the stimulation 
that could have been delivered actually was, during any period.  
4.13. Statistical Plan 
The Statistical Analysis Plan is a separate document which should be read in conjunction with 
this document. 
Post-hoc analyses may be conducted but will not form part of the PMA submission.  

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4.14. Trial Schema 
The Trial Schema is shown in outline in Figure 5. The summary data collection schedule is shown in Table 2. 
 
Figure 5: Trial Schema 
 
Informed Consent, 
Baseline data 
collection, 
inclusion decision 
ReActiv8 
Implant 
Randomization & 
Activation 
Time from Randomization 
12 Months 
1 
1 
2 
4 
5 
7 
8 
9 
11 
Visit Number 
Post Surg. 
Follow Up 
8 
Endpoint 
Assessment 
10 
10 
7 
5 
Treatment Arm 
Control Arm 
3 
0 
14 days 
75 Days 
120 Days 
180 Days 
240 Days 
9 
A 
Annual 
Crossover 
Group 
8a 
6 
6 
45 Days 

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Table 2: Summary Data Collection Schedule  
All Subjects  
 
T = Treatment Group Only 
 
1 Informed Consent, Baseline 
Data, Inclusion decision 
2 ReActiv8 Implant Procedure 
(1-45 days post inclusion) 
3 Post-Implant Follow Up 
(7 -0/+10 days 
4 Randomization and 
Activation (14 ± 3 days) 
5 14±7 Days Post 
Randomization 
6 45±7 Days Post 
Randomization 
7 75±10 Days Post 
Randomization 
8 Endpoint: 120 -0/+20 Days 
Post Randomization 
8a Crossover and Activation 
(Crossover Group only) 
9 180 ±30 Days Post 
Randomization 
10  240±30 Days Post 
Randomization 
11 12 Months -30/+60 Days 
Post Randomization 
 
Annual Follow Up 360 ±60 
Days Post Randomization 
 
Unscheduled Visit 
Screening data (including PIT) and MRI review 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psychological Assessment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ODI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Back Pain VAS (Journal) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Back Pain VAS (Single Point) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medications Questionnaire 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EQ-5D 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DASS21 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Low Back Pain Descriptive Characteristics  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Work Status Evaluation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Percent Pain Relief 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Subject Global Impression of Change (SGIC) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Treatment Satisfaction Questionnaire (TSQ) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Clinical Global Impression (CGI) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Health Care Utilization 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blinding Assessment Questionnaire 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X-Ray (AP and Lateral) 
 
 
 
 
 
 
 
 
 
 
 
 
 
? 
Device Measurements & Stimulation thresholds 
 
 
 
T 
T 
T 
T 
T 
 
 
 
 
 
 
Interrogate IPG for lead impedance & compliance 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Exam & Surgical Site Exam 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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5. 
Subject Selection and Withdrawal 
5.1. Inclusion Criteria 
1. Age ≥22c years, ≤75 years  
2. 7 day recall of Average Low Back Pain VAS of ≥6.0cm and ≤9.0cm at baseline (on a 10cm 
scale)  
3. Oswestry Disability Index score ≥21% and ≤60% at the Baseline Visit. 
4. Chronic Low Back Pain defined as pain and discomfort localized below the costal margin 
and above the inferior gluteal fold (with or without referred leg pain) that has persisted >90 
days prior to the Baseline Visit, which has resulted in pain in at least half of the days in the 
12 months prior to the Baseline Visit, as reported by the Subject. 
5. Evidence of lumbar multifidus muscle dysfunction by the Prone Instability Test (PIT). 
6. Continuing low back pain despite >90 days of medical management including: 
a. At least one attempt of physical therapy treatment for low back pain, which may 
optionally be accomplished over multiple episodes or flare-ups of low back pain. 
NOTE 1: Subjects who start a physical therapy program but are unable to complete it are 
still eligible with regards to this inclusion criterion. 
NOTE 2: Subjects who participated in a physical therapy program in the past since the 
onset of low back pain but are unwilling or unable to participate in a new physical 
therapy program are still eligible with regards to this inclusion criterion; 
b. For Subjects with medications prescribed and used for chronic low back pain, usage 
shall be at a stable dose in the 30 days prior to the Baseline Visit as reported by the 
Subject. 
NOTE 3: A stable dose means the Subject reports no significant change in regular use of 
medications, which may include PRN use, in the 30 days prior to the Baseline Visit. 
7. Be willing and capable of giving Informed Consent 
8. Ability to comply with the instructions for use and to operate ReActiv8, and to comply with 
this Clinical Investigation Plan. 
9. Suitable for ReActiv8 surgery as determined by the implanting physician prior to inclusion. 
5.2. Exclusion Criteria 
1. BMI > 35 
2. Back Pain characteristics: 
a. 
Any surgical correction procedure for scoliosis at any time, or a current clinical 
diagnosis of moderate to severe scoliosis (Cobb angle ≥25°). 
b. 
Lumbar spine stenosis, as defined by an anterior-posterior diameter of the spinal canal 
of <10mm in Subjects with lower extremity pain. 
c. 
Neurological deficit possibly associated with the back pain (e.g. foot drop).  
d. 
Back pain due to pelvic or visceral reasons (e.g.: endometriosis or fibroids) or infection 
(e.g.: post herpetic neuralgia). 
e. 
Back pain due to inflammation or damage to the spinal cord or adjacent structures (e.g. 
arachnoiditis or syringomyelia). 
 
C As per the FDA definition of an adult   

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f. 
Pathology seen on MRI that is clearly identified and is likely the cause of the CLBP that 
is amenable to surgery. 
g. 
Back pain due to vascular causes such as aortic aneurysm and dissection. 
3. An independent assessment of any current indication for back surgery according to 
appropriate guidelines, or has indications for back surgery but cannot undergo surgery for 
other reasons. 
4. Leg pain described as being worse than back pain, or radiculopathy (neuropathic pain) 
below the knee. 
5. Source of pain is the sacroiliac joint as determined by the Investigator. 
6. Drug use per Subject report as follows:d 
a. 
Current baseline use of >120mg oral morphine equivalent per day of opioids. 
b. 
Current use of breakthrough dose of >60mg oral morphine equivalent per day 
c. 
Current requirement of opioids for treatment of a condition other than low back pain. 
d. 
History of any substance abuse at any time in the five years prior to the Baseline Visit. 
e. 
Currently taking >15mg Diazepam per day or equivalent. (See Table 3)  
7. Surgical or other procedures exclusions: 
a. 
Any previous rhizotomy or rhizolysis procedure, including cryoablation, RF ablation or 
pulsed RF on the dorsal root ganglion (DRG) or the medial branch of the dorsal ramus 
nerve that crosses or lies below the T8 vertebra, within one year prior to the Baseline 
Visit. 
b. 
Anesthetic block of the DRG or medial branch of the dorsal ramus nerve that crosses 
or lies below the T8 vertebra or injection of epidural steroids for back pain in the 30 
days prior to the Baseline Visit. 
c. 
Any previous back surgery including laminectomy or discectomy at or below segmental 
level T8, or spinal fusion at any level. 
d. 
Any previous thoracic or lumbar sympathectomy. 
8. Any prior diagnosis of lumbar vertebral compression fracture, lumbar pars fracture, pars 
defect, or lumbar annular tear with disc protrusion that is amenable to surgery. 
9. Planned surgery: 
a. 
Any major surgery (including elective surgery) planned in the twelve months following 
the Baseline Visit (does not include minor surgeries not expected to impact the lumbar 
spine (e.g. colonoscopy)). 
b. 
Any elective surgery of any kind (including, for example, tooth extraction, gynecological 
surgery, or cosmetic surgery) in the time between the Baseline Visit and the Primary 
Endpoint Assessment Visit. 
10. Any co-morbid chronic pain conditions. 
11. Other clinical conditions: 
a. 
Pregnant or planning to be pregnant in the next 12 months, at the time of inclusion.e  
b. 
Pregnancy at any time in the 6 months, or lactating in the 3 months, prior to the 
Baseline Visit.  
 
d  
The reason for exclusion of Subjects on high doses of narcotics or anti-depressants is that these doses may have altered 
the CNS to the extent that the therapy may not work, there is a possibility of addiction that may not resolve even after back 
pain symptoms are reduced or eliminated, and there is a possibility that a significant portion of the Subject’s back pain 
symptoms are secondary to opioid induced hyperalgesia 
e  
Subjects will be advised that if they become pregnant or plan to become pregnant after the Primary Endpoint Assessment 
Visit, the Activator will be withdrawn and the IPG programmed to OFF to prevent any stimulation delivery during pregnancy. 
The IPG may be reprogrammed and the Activator returned if the Subject requests following completion or termination of the 
pregnancy.  

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c. 
Any condition unrelated to the CLBP such as muscle wasting, muscle atrophy, other 
disability (e.g.: paraplegic, amputee, cerebral palsy) or muscular or skeletal disease 
(e.g.: arthritis in trunk or limbs, multiple sclerosis, rheumatoid arthritis) which, in the 
opinion of the Investigator, could limit physical movement or compliance with the 
protocol, or interfere with the assessment of efficacy of the investigational procedure.  
d. 
Poorly controlled diabetes (Type I or Type II) determined by HbA1c >8. 
e. 
Past or current neurological disorders (e.g.: known multiple sclerosis, motor neuron 
disease, Guillain-Barré syndrome, Parkinson’s, Huntington’s Disease, Alzheimer’s, 
epilepsy, stroke, brain cancer, traumatic brain injury). 
f. 
Cancer requiring treatment during the study. 
g. 
Any drugs (e.g.: immunosuppressive drugs) or co-morbidity that might inhibit wound 
healing or electrode scarring, or drugs associated with reduced effectiveness of 
neuromodulation for other applications. 
h. 
Any medical condition requiring anticoagulation (other than aspirin) that, in the opinion 
of the physician prescribing the anticoagulant, cannot be safely suspended for 5 days 
prior to device implantation surgery and an appropriate period after implantation 
surgery. 
i. 
Any active infection in the vicinity of the implant site or any systemic infection. 
12. Psycho-social exclusions 
a. 
Be involved in an injury claim under current litigation.  
b. 
Have a pending or approved financial compensation claim (e.g.: worker’s 
compensation claim, long term disability claim) or any financial compensation (including 
social welfare payments) related to the Subject’s CLBP. 
c. 
Current incarceration (prison or jail) 
d. 
Have an assessment of current active depression significant enough (DASS 
depression score >9) to impact perception of pain, compliance with intervention and/or 
ability to evaluate treatment outcome. 
e. 
Have evidence of an active disruptive psychological or psychiatric disorder or other 
known condition significant enough to impact perception of pain, compliance with 
intervention and/or ability to evaluate treatment outcome (e.g.: active depression, 
bipolar disease, Alzheimer’s disease) as determined by a psychologist or psychiatrist. 
13. Protocol Compliance Exclusions 
a. 
Inability or unwillingness to comply with all protocol requirements. 
b. 
Inability to maintain the prone or side lying position in a relaxed manner for the duration 
of each stimulation session. 
c. 
Inability to operate the Activator, such as arthritis that limits arm or shoulder movement, 
or inability to learn how to operate. 
d. 
Inability to assess changes in pain intensity or perform wound care. 
e. 
Inability or unwillingness to complete the Journal. 
14. General exclusions 
a. 
Any other active implantable device including an implantable device for back pain (such 
as an implantable drug pump or Spinal Cord Stimulator), pacemaker, implantable 
defibrillator, cochlear implant, deep brain stimulator, implantable drug pump, or other 
implanted neurostimulation device. 
b. 
Prior exposure to an implantable neurostimulator for treatment of pain, including spinal 
cord stimulation (including trial implant of SCS leads), occipital nerve stimulation or 
peripheral nerve stimulation. 
c. 
A condition currently requiring or likely to require use of MRI or diathermy while 
implanted with the ReActiv8.  

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d. 
Therapy with any other investigational intervention (drugs, devices, or procedures) for 
the treatment of back pain at the time of the Baseline Visit, or at any time in the past if 
the past investigational intervention did not subsequently gain regulatory approval. 
e. 
Current or planned participation in any other clinical trial during participation in this 
Trial. 
f. 
Life expectancy <1 year 
Table 3: Benzodiazepine Equivalents 
Drug 
Dose Equivalent to 15mg Diazepam (mg) 
Alprazolam 
1.5 
Alprazolam extended release 
1.5 
Chlordiazepoxide 
30 
Clonazepam 
0.75 
Clorazepate 
22.5 
Estazolam 
0.9 
Flurazepam 
15 
Lorazepam 
3 
Oxazepam 
45 
Prazepam 
45 
Quazepam 
15 
Temazepam 
15 
Triazolam 
0.3 
5.3. Other Therapy During the Trial 
5.3.1. 
Medication 
Subjects shall be advised to not make any change to medications for treatment of low back pain 
at the time of the Subject’s inclusion in the Trial until the Primary Endpoint Assessment Visit. 
This includes medications for pain and muscle relaxants. Subjects will be informed that they 
may reduce, increase or discontinue medications for low back pain following the Primary 
Endpoint Assessment Visit.  
Subjects will be informed that if they believe they need any change in prescription medications 
for treatment of low back pain during the Trial, then they should contact the Investigator who will 
arrange for modification of type or dose of pain medications, as clinically necessary, and the 
data will be recorded. Subjects will be told that they should not request modification to 
prescribed drugs for their low back pain from any non-study physician during the period from 
baseline until the Primary Endpoint Assessment Visit. Any change in medications for other 
conditions (e.g.: hypertension) are allowed if prescribed by the Subject’s regular treating 
physician. 
All Subjects shall continue on any and all prescribed medication deemed medically necessary 
and not prescribed for the indication of CLBP (e.g.: antihypertensive medicines, statins, thyroid 
medications, diabetes medication, and low-dose aspirin).  

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Any change in pain medication prescribed and taken over the 14 days prior to the 120 day visit 
shall be reported by the Subject at the visit. If the prescribed dose is PRN, the Subject shall 
report the use of the drug over the prior two weeks if it changed from that taken at baseline. 
5.3.2. 
Physiotherapy & Exercise 
Subjects will be instructed to go about their daily lives as best as possible, and encouraged to 
be active. 
If the Subject has previously participated in an exercise program or other physical activity (e.g.: 
aerobic exercises, weight training, home exercise machine, team or solo sports) then that 
exercise may continue or resume at the discretion of the Investigator, following the 
Randomization Visit. Such exercise should not be performed between Implant and the 
Randomization Visit to allow time for healing of the surgical scar. 
Any additional exercise is to be allowed at the discretion of the Investigator, subject to the 
Subject’s ability to perform exercise. To avoid bias, no specific physiotherapy or other exercises 
to treat CLBP are allowed between the Baseline and Primary Outcome Assessment Visit.  
Strenuous activity that could exacerbate the underlying condition of low back pain shall be 
forbidden until after the Primary Endpoint Assessment Visit (e.g.: chopping wood, rowing, heavy 
weight lifting, and wrestling). 
5.3.3. 
Other Devices or Therapy 
Use of other devices or therapy is likely to confound the results of the Trial. Therefore, with the 
exception of medication, all therapies targeted at the low back pain will be prohibited during the 
Trial. Subjects should be instructed to not use any other devices such as braces, belts, TENs 
devices, acupuncture, chiropractic manipulation, massage or anything else which is not 
specifically required by this protocol. 
It is especially important that the following procedures not be performed during the Trial 
because they will directly affect the device itself and/or its ability to interact appropriately with 
the body, or may affect endpoint assessment: 
• 
Epidural injections 
• 
Nerve ablations of any kind for low back pain 
• 
Any other interventional pain procedures for low back pain (e.g.: nerve blocks) 
• 
Any physical procedure (e.g.: back or gluteal massage or chiropractic adjustment) that 
carries a risk of dislodging leads 

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6. 
Subject Contact and Data Collection Schedule 
Subject contact will be according to the following schedule. Any unscheduled visits will be 
recorded. 
Note: All data collection shall be done as the first thing in the follow up visit, prior to any other 
procedures. 
Note: Adverse event data will be collected at each visit after the Baseline Visit. 
6.1. Visit 1: Informed Consent, Baseline Data, Inclusion 
Decision 
The process for obtaining informed consent shall be in compliance with FDA regulations 
(21CFR 50) and ISO 14155. 
Subjects will be provided with the Subject Information and Informed Consent Form which 
advises that data will be collected for evaluation of eligibility for inclusion in the Trial. Subjects 
are told that if the criteria are met and the Subject consents, then the ReActiv8 will be 
implanted. 
If the Subject agrees to inclusion for data collection, the Subject Informed Consent will be 
signed and recorded in the Subject’s records at Visit 1. 
The Subject will be assigned a unique study identifier. 
Data to be collected during the visit: 
• 
Screening data as required by the inclusion/exclusion criteria documented in Subject study 
records 
• 
Medical History (including Physical Exam) 
• 
Low Back pain descriptive characteristics 
• 
7 day recall of Average Low Back Pain VAS as reported by the Subject 
• 
Work status evaluation 
• 
Medications (all medications including indication) 
• 
ODI 
• 
EQ-5D 
• 
DASS21 
• 
Healthcare Utilization 
Activities to be performed: 
• 
Journal: 
o 
Instruct the Subject in the use of the Journal and provide the Journal. 
• 
Prone Instability Test to assess lumbar multifidus dysfunction. 
• 
Answer any questions the Subject may have, and confirm willingness to proceed if the 
baseline criteria are verified. 
• 
Verify that the inclusion/exclusion criteria are satisfied. 

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• 
An MRI of the lumbar region of the low back will be performed or ordered if there are no MRI 
images from more recently than 180 days prior to Visit 1. MRI images will be reviewedf to 
assess conditions that may be a possible cause of low back pain and to rule out possible 
surgical candidates by institutional guidelines. 
• 
Pregnancy test in women of child bearing potential. 
• 
Assessment by the Investigator of the Subject’s suitability for ReActiv8 implant which 
includes review of the psychological assessment (e.g. mental fitness). 
NOTE: The surgical assessment and other required assessments may be performed at any 
time prior to Visit 2, and still be included in the Visit 1 data collected. If the implanting 
physician determines that the Subject is not a suitable candidate for the procedure, 
then the Subject shall not be scheduled for implant, will be withdrawn from the Trial, 
and will not be included in the analysis. 
• 
If the Subject meets the inclusion criteria, schedule the surgery for the ReActiv8 implant and 
discuss with the Subject. Ensure that all hardware necessary for the procedure is available, 
and schedule support staff. 
6.2. Visit 2: Implant Procedure 
The implant procedure should take place as soon as possible following the verification of 
baseline criteria, at a minimum of 1 day and maximum of 45 days following Visit 1. The duration 
of the implant procedure visit depends on local institutional practices and Subject condition post-
implant, and may be as short as a few hours (e.g.: for an outpatient procedure), or as long as 
several days. 
Data to be collected prior to implant:  
• 
Medications 
Data to be collected during or post implant: 
• 
Surgical notes  
• 
Adverse Events (including Adverse Events prior to the Implant Procedure, and any adverse 
events associated with the Implant Procedure). 
• 
Measurement and recording of electrode impedance and stimulation thresholds as defined 
in the Implant and Programming Manual 
NOTE: The Subject should preferably be unconscious (i.e.: general anesthesia) during 
assessment of electrode impedance and stimulation thresholds. If local anesthesia is 
used, then appropriate medication should be administered to minimize the chance 
that the Subject will remember the procedure. 
Activities to be performed after implant procedure: 
• 
Make a (de-identified) digital record of fluoroscopic images taken during the implant 
procedureg including at least bi-plane (AP and lateral) radiographic images of electrode 
position that shows the entire implanted system from the distal tip of the electrodes to the 
whole IPG. 
 
f  
All Images to be de-identified and included in the data record for the Subject in an electronic format to allow analysis at a 
later date. A core lab may be used for evaluation of MRI images as part of the supplementary data analysis. 
g  
It is a requirement for a site to participate in the trial that digital recording of fluoroscopic images should be available 

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• 
Inspect the surgical site prior to hospital discharge 
• 
Program IPG to OFF (i.e.: default state is no electrical output from the IPG). 
NOTE: Regular post-surgical follow up per institutional guidelines in the first 7 days post-
implant are included in the Implant Procedure Visit. 
6.3. Visit 3: Post-Implant 7 -0+10 Days  
A Post-Surgical Follow Up visit should be performed between 7 and 17 days post-implant. 
Data to be collected 
• 
Adverse Events 
Activities to be performed: 
• 
Examination of the surgical wounds (Physical Exam and Surgical Site Exam) 
• 
General post-surgical clinical care 
• 
Removal of sutures (Note: it is recommended that sutures be removed no sooner than 11 
days post-implant to reduce the risk of infection) 
6.4. Visit 4: Randomization & Activation Visit 14 ± 3 days 
Post Implant 
Randomization shall be 14 ± 3 days from the date of implant (to allow for scheduling). Visit 3 
and Visit 4 may be combined. 
If the Subject is unable to use the device for any reason (e.g.: injury, infection, other new clinical 
condition) at the time of the Randomization Visit, then the Randomization Visit may be 
postponed up to 30 days to allow the issue to resolve without incurring a protocol deviation. 
Note:  A decision to delay randomization must be done before the Subject is randomized. 
Data to be collected: 
• 
Adverse events 
Activities to be performed: 
• 
Inspect surgical wound to verify healing, and remove sutures (if not previously removed). 
Address any clinical issues associated with the surgical procedure (Physical Exam and 
Surgical Site Exam) 
• 
Confirm Subject allocation to Treatment or Control group has been completed. 
For Subjects in the Treatment Group Only: 
• 
Perform electrode impedance and threshold measurements and record results  
• 
Program IPG to Subject appropriate levels 
For Subjects in the Control Group Only: 
• 
Program IPG to Control 
For all Subjects: 
• 
Train in use of the Activator and document assessment of Subject’s ability to self-administer 
therapy twice a day starting the next day. 
• 
Train in the procedure to deliver stimulation, including time of day and Subject positioning. 

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• 
Provide encouragement to contact site personnel if any difficulty is encountered delivering 
stimulation or completing a Session. 
6.5. Visit 5: 14±7 Days Post Randomization 
Data to be collected: 
• 
Single point average low back pain VAS over previous week as reported by the Subject 
• 
Adverse events 
• 
AP and lateral X-Rays that clearly shows the entire implanted system from the distal tip of 
the electrodes to the whole IPG. 
Activities to be performed: 
• 
Inspection of surgical site (Physical Exam and Surgical Site Exam) 
• 
Provide the pain Journal and instruct the Subject in the use of the Journal for 7 days prior to 
the next scheduled visit. 
• 
Remind Subject to continue to lie down and activate therapy twice daily. 
• 
Readout from IPG of stimulation delivery times and duration (compliance assessment), 
battery state, and stored impedance measurements 
Note: Provide encouragement to all Subjects to continue to apply therapy using the Activator 
twice a day. If compliance assessment shows <90% compliance, additional counseling 
may be provided. 
For Subjects in the Treatment Group Only: 
• 
Device activities: 
o Electrode impedance and threshold measurements, and data collection 
o Adjustment of stimulation configuration and amplitude as appropriate 
6.6. Visit 6: 45±7 Days Post Randomization 
Data to be collected: 
• 
Pain Journal: 
o 
VAS for daily average low back pain 
• 
7 day recall of Average Low Back Pain VAS as reported by the Subject 
• 
Pain medications prescribed and taken 
• 
Low Back Pain descriptive characteristics 
• 
Work status evaluation 
• 
Adverse events 
Activities to be performed: 
• 
Inspection of surgical site (Physical Exam and Surgical Site Exam) 
• 
Collect Journal, and provide new Journal and instruct the Subject to continue to complete 
Journal assessments 7 days prior to the next scheduled visit. 
• 
Remind Subject to continue to lie down and activate therapy twice daily. 
• 
Readout from IPG of stimulation delivery times and duration (compliance assessment), 
battery state, and stored impedance measurements 

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Note: Provide encouragement to all Subjects to continue to apply therapy using the Activator 
twice a day. If compliance assessment shows <90% compliance, additional counseling 
may be provided. 
For Subjects in the Treatment Group Only: 
• 
Device activities: 
o Electrode impedance and threshold measurements, and data collection 
o Adjustment of stimulation configuration and amplitude as appropriate 
6.7. Visit 7: 75±10 Days Post Randomization 
Data to be collected: 
• 
Pain Journal: 
o VAS for daily average low back pain 
• 
7 day recall of Average Low Back Pain VAS as reported by the Subject 
• 
Low Back Pain descriptive characteristics 
• 
Work status evaluation 
• 
Oswestry Disability Index 
• 
EQ-5D 
• 
Pain medications prescribed and taken 
• 
Percent Pain Relief 
• 
Adverse events 
• 
Subject Global Impression of Change (SGIC) 
• 
Treatment Satisfaction Questionnaire (TSQ) 
• 
Clinical Global Impression – Global Improvement (CGI-I) 
Activities to be performed: 
• 
Inspection of surgical site (Physical Exam and Surgical Site) 
• 
Collect Journal, and provide new Journal and instruct the Subject to continue to complete 
Journal assessments 7 days prior to the next scheduled visit. 
• 
Remind Subject to continue to lie down and activate therapy twice daily. 
• 
Readout from IPG of stimulation delivery times and duration (compliance assessment), 
battery state, and stored impedance measurements 
Note: Provide encouragement to all Subjects to continue to apply therapy using the Activator 
twice a day. If compliance assessment shows <90% compliance, additional counseling 
may be warranted. 
For Subjects in the Treatment Group Only: 
• 
Device activities: 
o Electrode impedance and threshold measurements, and data collection 
o Adjustment of stimulation configuration and amplitude as appropriate 
 
 
 

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6.8. Visit 8: 120 -0/+20 Days Post Randomization  
This Primary Endpoint Assessment Visit must be performed no sooner than 120 days post 
randomization to ensure all Subjects have at least 120 days of treatment or control. At this visit 
Subjects in the Control group may now be programmed to appropriate stimulation levels and will 
be considered part of the Crossover group. 
Data to be collected: 
• 
Pain Journal  
o 
VAS for daily average low back pain 
• 
7 day recall of Average Low Back Pain VAS as reported by the Subject 
• 
Low Back Pain descriptive characteristics 
• 
Work status evaluation 
• 
Oswestry Disability Index 
• 
EQ-5D 
• 
Pain medications prescribed and taken 
• 
Percent Pain Relief 
• 
Subject Global Impression of Change (SGIC) 
• 
Treatment Satisfaction Questionnaire (TSQ) 
• 
Clinical Global Impression – Global Improvement (CGI-I) 
• 
Adverse events 
• 
Blinding Assessment 
Activities to be performed after endpoint data collection: 
• 
Collect Subject’s Journal 
• 
Inspection of surgical site (Physical Exam and Surgical Site Exam) 
• 
Device activities: 
o Electrode impedance and threshold measurements  
o Readout from IPG of stimulation delivery times and duration (compliance assessment), 
battery state, and stored impedance measurements 
o Adjustment of stimulation configuration and amplitude as appropriate 
• 
For Subjects in the Control group, assessment of thresholds and programming of the 
ReActiv8 IPG to a Subject appropriate level that result in strong smooth contractions of the 
multifidus. These Subjects now form the Crossover Group. 
Note: At the Primary Endpoint Assessment Visit, all Subjects are advised that they can vary 
their medications for back pain as needed or desired.  
6.9. Visit 8a: Crossover and Activation 
Subjects in the Crossover Group require additional activities and data collection, which may be 
done as part of Visit 8 or can be scheduled as an additional visit. 
Data to be collected: 
• 
Adverse events (after threshold assessment and IPG programming) 
Activities to be performed: 
• 
Device activities (if not already done): 
o Readout from IPG of stimulation delivery times and duration (compliance assessment), 
battery state, and stored impedance measurements 

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o Electrode impedance and threshold measurements, and data collection 
Adjustment of stimulation configuration and amplitude as appropriate 
6.10. Visit 9: 180 ± 30 Days Post Randomization  
Data to be collected: 
• 
7 day recall of Average Low Back Pain VAS as reported by the Subject 
• 
Low Back Pain descriptive characteristics 
• 
Work status evaluation 
• 
Oswestry Disability Index 
• 
EQ-5D 
• 
Pain medications prescribed and taken 
• 
Percent Pain Relief 
• 
Adverse event 
• 
Device measurements and stimulation thresholds 
• 
Subject Global Impression of Change (SGIC) 
• 
Treatment Satisfaction Questionnaire (TSQ) 
• 
Clinical Global Impression – Global Improvement (CGI-I) 
• 
Health care Utilization  
Activities to be performed: 
• 
Inspection of surgical site (Physical Exam and Surgical Site Exam) 
• 
Device activities: 
o Readout from IPG of stimulation delivery times and duration (compliance assessment), 
battery state, and stored impedance measurements 
o Electrode impedance and threshold measurements, and data collection 
o Adjustment of stimulation configuration and amplitude as appropriate 
6.11. Visits 10: 240 ± 30 Days Post Randomization 
Data to be collected: 
• 
7 day recall of Average Low Back Pain VAS over previous week as reported by the Subject 
• 
Low Back Pain descriptive characteristics 
• 
Work status evaluation 
• 
Oswestry Disability Index 
• 
EQ-5D 
• 
Pain medications prescribed and taken 
• 
Percent Pain Relief 
• 
Adverse event 
• 
Device measurements and stimulation thresholds 
• 
Subject Global Impression of Change (SGIC) 
• 
Treatment Satisfaction Questionnaire (TSQ) 
• 
Clinical Global Impression – Global Improvement (CGI-I) 
• 
Health care Utilization  
Activities to be performed: 
• 
Inspection of surgical site (Physical Exam and Surgical Site) 

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• 
Device activities: 
o Readout from IPG of stimulation delivery times and duration (compliance assessment), 
battery state, and stored impedance measurements 
o Electrode impedance and threshold measurements, and data collection 
o Adjustment of stimulation configuration and amplitude as appropriate 
6.12. Visits 11: 12 Months 0-30/+60 Days Post Randomization 
Data to be collected: 
• 
7 day recall of Average Low Back Pain VAS as reported by the Subject 
• 
Low Back Pain descriptive characteristics 
• 
Work status evaluation 
• 
Oswestry Disability Index 
• 
EQ-5D 
• 
Pain medications prescribed and taken 
• 
Percent Pain Relief 
• 
Adverse events 
• 
Device measurements and stimulation thresholds 
• 
Subject Global Impression of Change (SGIC) 
• 
Treatment Satisfaction Questionnaire (TSQ) 
• 
Clinical Global Impression – Global Improvement (CGI-I) 
• 
Health care Utilization  
Activities to be performed: 
• 
Inspection of surgical site (Physical Exam and Surgical Site Exam) 
• 
Device activities: 
o Readout from IPG of stimulation delivery times and duration (compliance assessment), 
battery state, and stored impedance measurements 
o Electrode impedance and threshold measurements, and data collection 
o Adjustment of stimulation configuration and amplitude as appropriate 
6.13. Annual Follow Up  
All Subjects will be scheduled for an Annual Follow Up following Visit 11 until such time as 
ReActiv8 obtains US regulatory approval or the Trial is abandoned. Following US regulatory 
approval, all Subjects who continue with ReActiv8 implanted will have continuing Annual Follow 
Up for 7 years from the date of randomization.  
Data to be collected: 
• 
7 day recall of Average Low Back Pain VAS as reported by the Subject 
• 
Low Back Pain descriptive characteristics 
• 
Work Status Evaluation 
• 
Oswestry Disability Index 
• 
EQ-5D 
• 
Pain medications prescribed and taken 
• 
Percent Pain Relief 
• 
Adverse events 
• 
Subject Global Impression of Change (SGIC) 

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• 
Treatment Satisfaction Questionnaire (TSQ) 
• 
Clinical Global Impression – Global Improvement (CGI-I) 
• 
Health care Utilization Inspection of surgical site (Physical Exam and Surgical Site) 
• 
Device measurements and stimulation thresholds 
• 
Device activities: 
o Readout from IPG of stimulation delivery times and duration (compliance assessment), 
battery state, and stored impedance measurements 
o Electrode impedance and threshold measurements, and data collection 
o Adjustment of stimulation configuration and amplitude as appropriate 
6.14. Unscheduled Visits 
If an unscheduled visit occurs for any reason, the following data will be collected prior to any 
other activities.  
• 
7 day recall of Average Low Back Pain VAS as reported by the Subject 
• 
Adverse events 
Activities to be performed: 
• 
Inspection of surgical site (Physical Exam and Surgical Site Exam) 
If an unscheduled visit occurs because of a suspected Adverse Device Effect (ADE) related to 
stimulation, then device testing shall be performed to investigate a suspected device failure. 
Other activities to investigate the suspected ADE (e.g.: X-Ray imaging) may be performed at the 
discretion of the physician. 
If an unscheduled visit occurs to perform a device explant for any reason (e.g.: infection 
necessitating device removal, elective removal at the request of the Subject), then additional 
data including surgical notes may be collected. Furthermore, any explanted devices or 
components shall be returned to the Sponsor following appropriate decontamination 
procedures. 
Note: If an unscheduled visit occurs prior to the Endpoint Data Assessment Visit for a Subject 
in the Control group, then all efforts shall be made to avoid potential unblinding of the 
Subject, particularly as a result of IPG testing which may inadvertently result in delivery 
of stimulation leading to Subject-perceived muscle contraction. 
6.15. Telephone Calls or Electronic contact 
The study coordinator will contact Subjects by telephone (or electronically) prior to each study 
visit starting with the 75 day visit through the 12 month visit. This contact will be to check on the 
well-being of the Subject, remind the Subject of the upcoming visit, remind Subjects to contact 
the Investigator/staff should he/she have any questions or concerns, remind Subjects to keep 
their pain medications the same as those taken at baseline, and to complete the pain Journal 7 
days prior to the 120 day visit. The telephone calls (or electronic contact) should be made within 
15-25 days prior to the scheduled visit date.  
 
 

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6.16. Revision/Explant Procedure 
Data to be collected prior to revision/explant:  
• 
Medications 
• 
Measurement and recording of electrode impedance as defined in the Implant and 
Programming Manual (system to be revised/explanted) 
Data to be collected during or post revision/explant procedure: 
• 
Surgical notes  
• 
Adverse Events 
• 
Measurement and recording of electrode impedance and stimulation thresholds as defined 
in the Implant and Programming Manual (newly implanted system) 
NOTE: If the procedure occurs prior to 120 days, then the Subject should preferably be 
unconscious (i.e.: general anesthesia) during assessment of electrode impedance 
and stimulation thresholds. If local anesthesia is used, then appropriate medication 
should be administered to minimize the chance that the Subject will remember the 
procedure. 
Activities to be performed after revision procedure: 
• 
Make a (de-identified) digital record of fluoroscopic images taken during the implant 
procedureh including at least bi-plane (AP and lateral) radiographic images of electrode 
position that shows the entire newly implanted system from the distal tip of the electrodes to 
the whole IPG 
• 
Inspect the surgical site prior to hospital discharge 
• 
Program IPG to OFF (i.e.: default state is no electrical output from the IPG) 
• 
Continue with study required visits. 
Activities to be performed after explant procedure: 
• 
Explant <120 days post randomization 
o Subject will be followed until the 120 day visit and then exited.  
• 
Explant >120 days post randomization 
o Adverse events will be collected over the last 30 days prior to exiting the study 
 
 
h  
It is a requirement for a site to participate in the trial that digital recording of fluoroscopic images should be available 

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7. 
Anticipated Benefits and Risks 
7.1. Anticipated Benefits 
The purpose of electrical stimulation of the medial branch of the dorsal ramus nerve with the 
ReActiv8 is to help restore neural drive to the lumbar multifidus muscle (LM). There are known 
clinical benefits to the restoration of neural drive to and rehabilitation of the LM when delivered 
by guided physical therapy with image guided biofeedback including: 
• 
Improvements in the disabling effect of low back pain 
• 
Improvements in severity of low back pain 
• 
Reduction in recurrence of low back pain 
• 
Improvement in ability to handle regular daily activities, including return to work 
• 
Improvements in Quality of Life 
Based on the Feasibility Study performed with other devices, there are expected benefits from 
the stimulation to be delivered by the ReActiv8, including decrease in low back pain, decrease 
in disability, and improvements in quality of life.  
There may be no benefits to the Subject as a result of participation in this Trial. 
7.2. Anticipated Risks 
All medical device treatments have the potential to cause adverse events or side effects. 
Adverse events are expected to be similar to other neurostimulation devices for treatment of 
back pain, such as spinal cord stimulators. Listed in this section are both known risks with spinal 
cord stimulators and peripheral nerve stimulators as well as theoretical risks for the ReActiv8. 
Additional information on risks and anticipated adverse events is to be found in the Implant and 
Programming Manual, which also includes warnings and precautions. 
Anticipated Adverse Events include: 
• 
AEs associated with the surgical procedure, including implant, revision, replacement and 
removal.  
o Acute or persistent pain including more pain than anticipated after surgery or worsened 
low back pain  
o Accidental injury to adjacent tissues, e.g. piercing structures such as muscle, blood 
vessels, nervous tissue, or organs  
o Anxiety about surgical procedure or outcome of therapy (beyond what is reasonably 
expected)  
o Infection, including local infection of the device or surgical site, systemic infection and 
sepsis  
o Respiratory arrest, e.g. apneic spell during surgery  
o Slow, abnormal or inadequate wound healing including swelling, hematoma, seroma, or 
wound dehiscence, which may require surgical repair  
o Nerve irritation, impingement or damage, including pain, paralysis, sensory deficits or 
changes to bowel, bladder or reproductive function  
o Scarring or inflammation associated with the surgical site (beyond what is reasonably 
expected)  
o Stiffness or restriction in movement  
o Death  

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o Risks associated with any surgical procedure, regardless of type, including prolonged 
procedure or sequelae of anesthesia  
o Bleeding, hematoma, and bruising  
o Swelling (beyond what is reasonably expected), seroma, or cyst  
o Abandonment of implant procedure, including due to failure to achieve suitable 
stimulation thresholds in one or both leads  
o Intraoperative difficulties implanting the device, such as inadequately seating lead into 
connector or damage to lead insulation  
o Tissue reaction to the presence of the implanted device or materials in/on the implanted 
device such as response to residual material on device or an allergic response, e.g. 
previously unknown nickel or titanium allergy. Reaction may be local or systemic.  
• 
AEs associated with presence and use of the device. This includes AEs associated with 
chronic implant whether or not the device is turned on.  
o Migration of the lead, which may result in surgical revision, replacement or removal of 
device  
o Device failure including failure of the IPG, failure of the lead, or failure of any other 
implanted component which may necessitate surgical revision, replacement, or removal 
of the device or components of the device. 
o Nerve irritation, impingement or damage, including that resulting from mechanical 
presence of device, exposure to electricity including electrical stimulation, or migration of 
the leads, suture sleeve or IPG. This may lead to pain, paralysis, sensory deficits or 
changes to bowel, bladder or reproductive function  
o Device extrusion  
o Erosion, threatened erosion or fistula formation in skin overlying device components  
o Excessive fibrotic tissue growth, including fibrotic tissue growth which may complicate 
device removal.  
o Hematoma, seroma, cyst or swelling  
o Acute or persistent pain including worsened low back pain and/or pain and discomfort 
due to presence of the device  
o Undesired sensations such as uncomfortable paresthesia, numbness, vibration, 
pressure, prickling, or uncomfortable contraction of the multifidus  
o Overstimulation of tissue, resulting in symptoms such as painful muscle contraction, 
paresthesia, jolts or shocks. In addition, injuries that occur as a consequence of 
stimulation, e.g. accidents that occur as a result of being startled or back injuries that 
occur due to diminished motor control  
o Infection, including local infection of the device or surgical site, systemic infection and 
sepsis  
o Death  
o Tissue reaction to the presence of the implanted device or materials in/on the implanted 
device such as response to residual material on device or an allergic response, e.g. 
previously unknown nickel or titanium allergy. Reaction may be local or systemic.  
o Skin irritation as a result of contact with the Activator 
o Tissue damage due to mechanical presence of device, or exposure to electricity 
including electrical stimulation  
o Contraction of muscles other than the target muscle(s)  
o Muscle fatigue, spasm or injury  
o Malfunction of other medical equipment such as a pacemaker due to device interactions 
o Stiffness, including restricted motion due to adhesions to the device  
o Psychiatric disturbance, such as anxiety or depression or complications of depression 
such as suicide  

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o Symptoms in unrelated systems such as nausea, insomnia, urinary retention or 
undesired weight changes, including as a sequelae of stimulation of the Subject. 
o Inability to deliver therapy, including inadequate doses of therapy. Sources include lead 
migration, device malfunction or exposure to electromagnetic fields, e.g. security 
screening devices  
o Electrical shock  
o Inability to stop therapy, with possible sequelae such as anxiety, restriction of 
movement, pain, muscle fatigue, postural changes, difficulty in walking, sitting or 
physical activity  
o Accidents, injuries, body movements, body positions or biological process which lead to 
device complications such as a fall which causes injury to the IPG, sit-ups or severe 
coughing leading to migration of the lead, or bony fracture leading to device migration or 
fracture. 
Subjects may also undergo medical/and or surgical intervention to treat the issues identified 
above. 
The ReActiv8 includes features that provide protection from EMI. Most electrical devices and 
magnets encountered in a normal day are unlikely to affect the operation of the ReActiv8. 
Sources of strong EMI can exist near high power amateur radio transmitters, near television 
towers or other equipment. Generally, the amount of EMI present in publicly-accessible areas is 
reduced to a level that is not likely to impact the ReActiv8. Exposure to strong sources of EMI 
can result in the following effects:  
o Serious injury or death, resulting from heating of the implanted components of the 
ReActiv8 and damage to surrounding tissue. 
o Damage to the ReActiv8, resulting in a loss of or change in stimulation delivery and 
requiring surgical replacement. 
o Operational changes to the ReActiv8 IPG, causing it to turn ON or OFF (particularly if 
the IPG is enabled for magnet use) or to reset, resulting in loss of stimulation and 
requiring reprogramming by a clinician. 
Equipment such as retail theft prevention systems and airport metal detectors may interfere with 
the ReActiv8. The Subject should be instructed to walk directly through such systems and not 
remain near them any longer than necessary. The presence of an implantable pulse generator 
in the body may set off security screening devices (e.g.: at airports), so it will be necessary for 
the Subject to carry a card to identify themselves to security screeners as carrying an IPG.  
Subjects with either the study device implanted or parts of the study device still implanted will 
not be able to have a magnetic resonance imaging (MRI) scan, since this test may damage the 
study device and may cause serious injury. This risk is unchanged as long as the system (IPG 
and leads) remains implanted. 
7.3. Risk Minimization  
Additional risks may exist. Risks can be minimized through the use of strict compliance with this 
CIP, and adherence to the guidelines for Subject selection, site training, and close monitoring of 
the Subject’s physiologic status at follow-up visits. In addition, the product labeling (including the 
Implant and Programming Manual and the User Manual) details warnings and precautions 
which must be followed to minimize risk to Subjects. 

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8. 
Safety 
The following definitions are used: 
Adverse Event (AE): 
An adverse event is defined as any undesirable clinical occurrence that affects the 
health or safety of the Subject.  
If an adverse event leads to multiple outcomes that sequentially worsen, only the worst adverse 
event is reported. For example, a hematoma leading to infection would be reported as a single 
AE for the infection. 
Serious Adverse Event (SAE): 
A Serious Adverse Event is defined as an adverse event that led to death, or led to 
serious deterioration in the health of the Subject, that either resulted in:  
1. a life-threatening illness or injury, or  
2. a permanent impairment of a body structure or a body function, or 
3. in-patient or prolonged hospitalization,  
4. congenital anomaly/birth defect, or  
5. medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
Note: Planned hospitalization for a pre-existing condition or a procedure required by 
the protocol (e.g., the index implant procedure, or device replacement due to 
normal battery depletion), without serious deterioration in health, is not 
considered a serious adverse event. 
Unanticipated Adverse Device Effect (UADE): 
An unanticipated adverse device effect means any serious adverse effect on health or 
safety or any life-threatening problem or death caused by or associated with a device, if 
that effect, problem, or death was not previously identified in nature, severity, or degree 
of incidence in the investigational plan or application, or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare of Subjects. 
For all adverse events the Investigator must determine whether the event was related to the 
device and/or procedure and document this on the eCRF. Individual events may be related to 
more than one category, e.g. an injury due to a tunneling tool may be related to Device 
Hardware and Procedure. The categories used for relatedness are listed in Table 4.  
Table 4: Adverse Event Relatedness Categories 
Related to Device Hardware  
Events reasonably anticipated to be related to the physical 
presence of the device, e.g. erosion, a device deficiency, 
loss of power. 
Related to Device Stimulation Events reasonably anticipated to be related to electrical 
stimulation, especially those that appear when the device 
is on and disappear when the device is off, e.g. undesired 
sensation experienced only when the device is turned on. 
Related to Procedure 
Events reasonably anticipated to be related to procedures 
described in this protocol. 

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All AEs will be collected from the time of informed consent through the end of the study. Death 
should not be recorded as a separate adverse event, but rather as an outcome of the specific 
SAE which led to the Subject’s death. 
Adverse Events that would be reasonably expected to be associated with any surgical 
procedure (e.g.: anesthesia associated nausea, surgical site pain) will not be categorized as 
procedure or device related in the 30 days post the surgical procedure (to be adjudicated by the 
Adjudication Committee). 
The Adjudication Committee will review and adjudicate all Adverse Events that occur, including 
relatedness. The Committee will also review and adjudicate all reported hospitalizations, 
regardless of whether they are classified by the Investigator as an adverse event. Safety 
Analysis will be performed on adjudicated events only. 
Notes: 
1. Any current condition that is recorded as a pre-existing condition is not an AE, unless 
there is a worsening of that condition in terms of nature, severity, or degree of incidence. 
2. Technical observations – an undesirable device event that does not result in a medically 
undesirable situation for the Subject – is not an AE. 
3. Normal end of battery life of the IPG is not an AE. 
4. Suspending or stopping use of ReActiv8 due to pain relieved is not an AE. 
5. ReActiv8 removed due to pain relieved is not an AE. 
6. Planned hospitalization for a procedure required by this protocol is not an AE. However, 
complications during the course of that planned hospitalization that prolong the 
anticipated duration of the hospitalization do constitute SAEs. 
7. Elective hospitalization for a pre-existing illness does not constitute an SAE unless the 
illness has worsened in the nature, severity or degree of the condition with respect to 
baseline. 
8. Device migration will not be collected as an AE, but rather as a device deficiency. If 
device migration results in a clinical symptom, report this as an AE in addition to the 
device deficiency report documenting device migration. 
9. Experiencing unusual sensations is a normal part of programming a neurostimulation 
device. Accordingly, symptoms felt during a programming session are not considered 
AEs unless they are caused by the final programming parameters and persist after 
completion of the programming session. 
10. Lack of efficacy or diminished therapeutic response does not constitute an AE since 
failure to receive therapeutic benefit is an issue of efficacy, not safety. This includes 
symptoms that recur in the context of device deficiency leading to loss of therapy. If the 
recurring symptoms are not worse than at baseline, record the event as a device 
deficiency but not as an adverse event. 
11. Removal and/or replacement of any part of the device due to malfunction would be 
considered a device related adverse event. 
8.1. Adverse Event Reporting  
The Investigator will monitor the occurrence of adverse events for each enrolled Subject. 
Adverse events reported by the Subject to the Investigator, confirmed by the Investigator, and 
documented in medical records must be reported on the adverse event form based on the 
requirements of the study CIP.  
All Adverse Events, all Serious Adverse Events, and all Unanticipated Adverse Device Effects 
will be reported to all Investigators and IRBs and/or Ethics Committees participating in the study 

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per their reporting requirements. This is done by means of an interim report or a final study 
report prepared by the Sponsor.  
8.2. Adverse Event Outcome Status  
Adverse Events, when reported, are assigned a status by centers depending on the nature of 
the event or the corrective action involved. When clinically appropriate, centers should work to 
close events whose underlying clinical condition may not be resolvable during the term of the 
investigation.  
Centers may move outcome status to “closed” or alternatively, add text to the adverse event 
description at a follow-up visit addressing that adverse event stating that the adverse event is 
ongoing but for study purposes and outcome data, the event is considered closed. 
8.3. Device Deficiencies 
A device deficiency is an inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance. All suspected investigational device deficiencies 
should be documented on the appropriate CRF. The Sponsor will investigate all suspected 
device deficiencies. 
Note: a device deficiency can include a device malfunction (i.e.: failure to perform to 
specifications), and may also include other deficiencies (e.g.: ambiguity of labelling). 
For the implanted components of ReActiv8, note that not all device deficiencies will lead to an 
explant. For example, loss of stimulation on one electrode may be resolved by reprogramming 
such that stimulation can be delivered on a different set of electrodes. Thus a device deficiency 
may not necessarily lead to an AE or SAE. 
If possible, a device with a suspected malfunction should be returned to Mainstay for analysis, 
including any explanted components. If it is not possible to return the device, the reason it could 
not be returned as well as its final disposition should be documented.  
Note that reporting of device deficiencies shall be separate from adverse event reporting. If 
there should be an adverse event associated with the device deficiency, then that adverse event 
should be reported on an adverse event CRF.  
8.4. Subject Deaths  
A Subject death during the study should be reported to the Sponsor as soon as possible and, in 
any event, within two working days of notification to the Investigator. The center’s IRB or Ethics 
Committee must be notified of any deaths in accordance with that center’s IRB or Ethics 
Committee policies and procedures. 
Notification of death should include a detailed narrative (death letter) that provides detailed 
information describing the circumstances surrounding the death and is signed by the principal 
Investigator or authorized Sub-Investigator. The death letter should include all of the following:  
• 
Date and time of death 
• 
Place death occurred 
• 
Immediate cause of death 
• 
Whether or not the death was witnessed 
• 
Device status and/or activity at the time of death, if known  
• 
Any other circumstances surrounding the death 

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• 
Approximate time interval from the initiating event to death (temporal course) 
• 
Investigator or sub-Investigator signature and date 
Any information listed above that is unavailable or unknown must be specified as such in the 
death letter.  
If the Subject expired in the hospital, the following documentation should also be submitted: 
• 
A copy of the medical records for that admission (e.g., consults, test results, operative 
reports, and/or progress notes from the hospital chart) 
• 
Death certificate (if available) 
• 
Autopsy report (if applicable) 
If the Subject expired outside of the hospital (e.g., home): 
• 
A copy of the most recent clinic visit (if not already submitted to the Sponsor) 
• 
Death certificate (if available) 
As applicable per local country regulation, the event should be reported by the Investigator to 
the appropriate regulatory bodies. 
Note that in the event of the death of a Subject with an implanted IPG, if cremation is planned, 
then the IPG must be explanted prior to cremation. The internal battery may explode when 
exposed to extreme heat.  

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9. 
Data Management 
9.1. Study Assessments 
The Sponsor will be responsible for collection of the data required for this study in accordance 
with record and reporting requirements listed in FDA 21CFR812 and Part 11. The Sponsor will 
use an electronic clinical database which shall have written procedures and document 
requirements. The Sponsor or its designated CRO(s) will verify and validate that the 
requirements for an electronic data system to receive and process data can be consistently met. 
Security, reliability, consistency of the data will be maintained throughout the study. Electronic 
CRF’s will be used on this study. Only those staff at each site that are identified and designated 
by the Investigator and trained on eCRF data entry system will be allowed access to the eCRF 
system. Any study assessment questionnaires that required the Subject to complete directly, will 
be done on paper CRF’s then transferred to the eCRF system by the designated study site 
personnel. 
The electronic case report forms, and paper CRFs will reflect the contents of this study protocol. 
The CRF’s and any amendment to them will bear a version date and each page will be 
identifiable by the study, site and Subject identification numbers. If it is necessary to amend the 
CRF’s, the Sponsor will review the study protocol to determine whether or not an amendment to 
the protocol is necessary. Study assessments may be recorded using paper notes from which 
data are transcribed into the eCRF, may include data recorded as per institutional practice (hard 
copy or electronic), or may be recorded directly into the eCRF, as appropriate. 
9.1.1. 
Medical History 
Medical history collected will include characteristics of the Subject’s low back pain such as 
diagnosis and duration, as well as number of episodes of low back pain as well as the 
medications and procedures for treatment of low back pain that the Subject has failed. 
The medical history will include baseline demographics as well as a small set of clinical data 
that would be collected at a typical visit to a general practitioner. 
Collection Method: Information transferred to paper CRFs or eCRF 
9.1.2. 
Subject Screening/Baseline  
Subject baseline and screening data collected shall include basic information (e.g., Subject 
identifier, date of enrollment, etc.) as well as a review of inclusion criteria, and a review of 
exclusion criteria. 
Additional data such as results of a pregnancy test (if applicable) and MRI shall be recorded as 
per institutional practice and the results included in the eCRF. 
Collection Method: Information transferred to paper CRF or eCRF if part of the site source 
documents. 
 
 

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9.1.3. 
Depression Anxiety Stress Scale (DASS21) 
The DASS21 is a paper questionnaire completed by the Subject alone and without assistance 
and results are recorded in the eCRF. Validated language specific versions are available.  
Collection method: Completed by the Subject on a paper questionnaire then transferred to the 
CRF or eCRF. 
9.1.4. 
Surgical Procedure 
Surgical procedure data collected shall include relevant information during and following the 
procedure. 
Collection Method: Transferred from source documents and surgery worksheets to paper CRF 
or eCRF 
9.1.5. 
Post-Operative Evaluation 
Evaluation of Subject post-operative status will be collected at the Post-Implant Follow-up. 
Collection Method: Transferred from source documents to paper CRF or eCRF 
9.1.6. 
Physical Exam and Surgical Site Exam (Post Implant) 
After implant, inspect the surgical site and note if healing is normal and as expected. Other 
elements of the physical exam include weight and information on any new clinical conditions not 
associated with the Trial.  
Collection Method: Transferred from source documents to paper CRF or eCRF 
9.1.7. 
Oswestry Disability Index 
The Oswestry Disability Index is a paper questionnaire completed by the Subject alone and 
without assistance and results are recorded in the eCRF. Validated language specific versions 
are available. 
Collection method: Completed by the Subject on a paper questionnaire then transferred to the 
CRF  
9.1.8. 
Low Back Pain VAS 
Low back pain VAS will be collected at each visit.  
Collection Method: Subject completes a form without assistance, and the results are transferred 
to the eCRF. 
 
 
 
 

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9.1.9. 
Medication 
All prescribed medications used, regardless of indication, will be collected at the time of Subject 
Screening/Baseline Visit. 
Medication endpoints will use the subset of this data comprised of prescribed pain medications 
and muscle relaxant 
• 
Primary endpoint assessment - the metric will be based on all prescribed pain 
medications or muscle relaxants taken.  
• 
Secondary endpoint assessment - the metric will be limited to opioids taken for treatment 
of low back pain. 
Collection Method: Question asked by the Study Coordinator and recorded then transferred to 
the eCRF. 
9.1.10. 
Treatment Satisfaction Questionnaire 
Treatment Satisfaction Questionnaire will consist of the questions shown in Figure 6. 
Are you satisfied with the outcome of your treatment? 
□ Definitely yes 
□ Maybe 
□ Definitely not 
Knowing what you know now, would you want this treatment again? 
□ Definitely yes 
□ Maybe 
□ Definitely not 
Would you recommend this treatment to another person with chronic low back pain? 
□ Definitely yes 
□ Maybe 
□ Definitely not 
Figure 6: Treatment Satisfaction Questionnaire 
Collection Method: Subject completes a paper form and results are transferred to paper CRF or 
into the eCRF 
9.1.11. 
Subject Global Impression of Change 
Subject Global Impression of Change consists of the questionnaire as detailed in 4.6.5. 
Collection method: Subject completes a paper form and results are transferred to paper CRF or 
eCRF 
9.1.12. 
Clinical Global Impression – Global Improvement 
Clinical Global Impression – Global Improvement consists of the questions that are to be 
completed by the Investigator as shown in Figure 3 on Page 28. 
Collection method: Physician completes on a paper CRF which is transferred to eCRF 

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9.1.13. 
EQ-5D 
The EQ-5D-5Li Quality of Life questionnaire is completed by the Subject. Validated language 
specific versions are available. 
Collection method: Subject completes a paper form and results are transferred into the eCRF 
9.1.14. 
Adverse Events 
All transient and long-term adverse events will be collected throughout the course of the study. 
Assessment will include Investigator-assessed relationship to device, relationship to procedure, 
severity (i.e.: AE or SAE), subsequent treatment/intervention required and resolution status at 
each follow-up visit until the event is resolved or closed because of chronic nature of the event. 
Note that a Subject death automatically closes any outstanding adverse events for that Subject. 
Collection Method: Paper CRF or eCRF 
9.1.15. 
Device Deficiency 
Device deficiency data collection will include all device deficiencies, including suspected device 
malfunctions and deficiencies. 
Collection Method: Paper CRF or eCRF 
9.2. Management of Protocol Deviations 
An Investigator is required to conduct this study in accordance with the signed Investigator's 
Agreement, this investigational plan, applicable laws and applicable national regulations, and 
any conditions of approval imposed by the reviewing IRB or Ethics Committee and regulatory 
agency (e.g.: FDA or Competent Authority). 
Protocol deviations are a fact of life with any clinical trial. Deviations may be anticipated (e.g.: 
known delay in a follow up visit), inadvertent (e.g.: unplanned delay or miss of a follow up visit 
due to a family emergency), or unanticipated on an emergency basis (e.g.: trauma may require 
device removal to allow an MRI, or other contraindicated procedures).  
Except in emergency situations, protocol deviations require prior Sponsor approval; and if the 
deviation may affect the scientific soundness of the plan or the rights, safety, or welfare of 
Subjects, prior IRB or Ethics Committee approval is required. 
An Investigator shall notify the Sponsor and the reviewing IRB or Ethics Committee of any 
deviation from the investigational plan to protect the life or physical well-being of a Subject in an 
emergency. Such notice shall be given as soon as possible, but no later than five working days 
after the emergency occurred.  
All deviations from the investigational plan must be reported to the Sponsor together with the 
reason for the deviation and possible corrective actions for the deviations. In some 
circumstances, the center may be required to notify the center’s IRB or Ethics Committee, and 
the Sponsor will notify the appropriate regulatory agencies. 
 
i  
See http://www.euroqol.org/  

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9.3. Informed Consent 
Informed Consent is required from all Subjects (or their legal representatives) prior to the 
Subject’s participation in the study. The process of obtaining Informed Consent shall comply 
with the Declaration of Helsinki, FDA 21CFR 50, ISO 14155-2011 and applicable national 
regulations (local IRB, Ethics Committee and/or Regulatory bodies, as applicable). 
The process of obtaining informed consent shall 
a) Avoid any coercion of or undue influence of Subjects to participate, 
b) Not waive or appear to waive Subject’s legal rights, 
c) Use native language that is non-technical and understandable to the Subject or his/her 
legal representative, 
d) Provide adequate time for the Subject to consider participation and ask questions if 
necessary, 
e) Informed consent shall always be signed and personally dated by the Subject or legal 
representative and by the Investigator or delegate. 
The original signed Informed Consent must be retained on file by the Investigator and a copy 
given to the Subject (Investigator’s responsibility).  
9.4. Subject Classification  
All Subjects are classified as one of the following:  
 
Baseline withdrawal – refers to a Subject who has been enrolled but then is withdrawn from 
the study before the device implant process has been initiated. The original Informed 
Consent form for intent Subjects should be maintained in the Centre’s administrative files. 
There are no follow-up requirements for Baseline withdrawal Subjects. 
 
Attempt – refers to a Subject who has been enrolled, and in whom a ReActiv8 implant was 
attempted (i.e.: attempt to place at least one lead) but was not completed.j All Subjects in 
whom the implant was unsuccessful will be followed for at 30 days following the implant 
attempt. If there are any AEs or SAEs associated with the attempted implant, the Subject 
will be followed until resolution or closure of the AE or SAE. 
 
Implant – refers to an enrolled Subject whose implant was completed (i.e.: device remains 
implanted and the surgical wound is closed and dressed). 
 
Withdrawal post implant – refers to a Subject who is determined to be inactive in the study 
due to physician discretion, Subject choice, lost to follow-up, or Subject death. Final status 
information will be included on all Subjects as available per the Informed Consent 
document.  
9.5. Subject Data Confidentiality  
Throughout the study, confidentiality shall be maintained at all times, by all parties involved, and 
all data shall be secured against unauthorized access. Confidentiality of each Subject shall be 
preserved in reports and any publication of the results. Only authorized personnel and their 
designees will have access to these confidential files. Subject data may be made available to 
national and foreign regulatory agencies, health or other governmental authorities, under strict 
confidentiality condition. The investigational sites shall ensure that data (e.g. worksheets, 
 
j  
Only one procedure for ReActiv8 implant should be attempted for each Subject, although each procedure may include 
multiple attempts to implant, e.g.: to allow for surgical challenges and need for lead repositioning. 

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programmer printouts, medical records, digital images) forwarded to the Sponsor do not contain 
any Subject identifying data (such as name and birth date) other than the Subject ID. 
It is required that CRFs be entered in the electronic data entry system provided by the Sponsor. 
All CRFs require the Investigator's signature or the Investigator’s designee.  
Source documents as per FDA 21CFR 812 and ISO 14155-2011 are printed, optical or 
electronic documents including the information in original records and necessary for the 
reconstruction and evaluation of the clinical investigation. Original source data should remain at 
the investigational site. 
Any changes of the reported data should be reported to the Sponsor. When available, changes 
should be entered into the electronic discrepancy management system provided by the 
Sponsor. A participating Investigator shall provide direct access to source data and documents 
for Trial-related monitoring, audits, IRB or Ethics Committee review, and regulatory inspection. 
All Subjects’ health information will be kept confidential in accordance with all applicable laws 
and regulations. Subjects’ health information may be used to conduct this research, as well as 
for additional purposes, such as overseeing and improving the performance of products, new 
medical research and proposals for developing new medical products or procedures, and other 
business purposes. Information received during the study will not be used to market to Subjects; 
Subject names will not be placed on any mailing lists or sold to anyone for marketing purposes.  
9.6. Record Keeping  
Investigators are required to maintain on file the accurate, complete, and current records 
relating to this investigation: 
• All correspondence with another Investigator, an IRB or Ethics Committee, Mainstay Medical, 
a monitor, or FDA or Competent Authority including required reports 
• The signed CIP with any and all amendments 
• The approved template of the Subject informed consent form 
• Records showing receipt, use, and disposition of all devices (including software), including: 
o Date, quantity, and serial numbers of devices received 
o Names of all persons who received, used or disposed of each device 
o Dates and serial numbers of devices returned to the Sponsor and the reason(s) for return 
• IRB or Ethics Committee approval of the CIP and any amendments and renewals 
• Competent Authority Approval in those countries where is applicable 
• The Investigators’ agreement and the fee agreement (separate or combined) 
• The Report of Prior Investigations and/or the Investigator’s Brochure 
• The insurance certificate  
• The Implant and Programming Manual and any other documentation provided with the 
device 
• Current curriculum vitae for the principal Investigator and all Sub-investigators 
• Monitoring letters (if applicable) 
• Interim/final reports 
• Study initiation forms 
• Study closure documents 
 

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In addition, to the study administrative documents, Subject records shall be appropriately filed, 
including the following: 
• Signed informed consent forms 
• Source documents used for recording data (e.g., device characteristics at implant and follow-
up) 
• Records of any adverse event, including supporting documentation 
• Records pertaining to Subject deaths during the study 
• Relevant source data 
• Any other records required by the Sponsor  
• Documents showing the dates and reasons for each deviation from the CIP 

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10. Study Management 
10.1. Committees and Independent Review 
10.1.1. 
Data Monitoring Committee  
A Data Monitoring Committee (DMC, or sometimes referred to as a Data and Safety Monitoring 
Board or DSMB) will be established according to ISO 14155, FDA and NIH guidelines, and will 
consist of experienced and knowledgeable professionals who are not Investigators. The DMC 
will meet periodically, or as needed, to review the results of the study and to provide safety 
oversight and professional input to make recommendations for the continuation or termination of 
the study based on data analysis and study related adverse events. The members of the 
committee will have access to all adverse event data and any other requested study data that 
would be necessary in order for the group to make an assessment relative to Subject safety.  
10.1.2. 
Adjudication Committee 
As per ISO 14155, the Sponsor is responsible for the classification of adverse events and 
ongoing safety evaluation of the clinical investigation.  
An Adjudication Committee will be established to adjudicate reported AEs. 
The Adjudication Committee will consist of at least three independent physicians (i.e.: not 
Investigators), of whom two will form a quorum, and none are also members of the DMC. The 
activities will be governed by a Charter. 
10.1.3. 
Independent Assessment of Surgical Candidacy 
If the site determines that the subject is not excluded based on the MRI assessment, the site will 
upload the relevant images to a Core Lab for storage and preparation for review by an 
Independent Physician Reviewer. An appropriately trained independent physician will review the 
Subject’s MRI to assess any current indication for back surgery according to appropriate 
evidence or guidelines (e.g.: Evidence Informed Management of Chronic Low Back Pain with 
Surgery,68 the Guidelines of the American Pain Society,69 or the European Guidelines for 
Management of Chronic Non-Specific Low Back Pain2). The activities will be governed by a 
Charter.  
10.2. Study Principal Investigator Review  
The Study Principal Investigator will review Baseline data for all subjects to confirm that they 
meet the eligibility criteria for the trial. This review will take place prior to the study implant 
procedure (Visit 2) and will be communicated to the Site Principal Investigator and study staff. 
The review may be performed by the Study PI or an alternate physician designated by the Study 
PI.  
10.3. Procedures to Amend the Clinical Investigation Plan 
From time to time, an Investigator or the Sponsor may propose changes to the Clinical 
Investigation Plan. The Sponsor shall have final authority to make such changes or not. 

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From time to time, the DMC may mandate or recommend changes to the Clinical Investigation 
Plan. From time to time, regulatory authorities may mandate or recommend changes to the 
Clinical Investigation Plan.  
All amendments to the CIP shall be agreed upon by the Sponsor and the Investigators and be 
recorded with a justification for the amendments. In all cases of changes to the Clinical 
Investigation Plan, the local rules for approval of modifications shall be followed, including by 
way of example a submission to the IRB or Ethics Committee (either in full or to the Chairman), 
and modifications to the clinical Trial contract with the institution if applicable. 
10.4. Device Accountability 
Device accountability shall be in compliance with ISO 14155 and FDA regulations. 
The Sponsor will control the availability of all investigational devices (including software) by 
shipping devices only to trained representatives or study Investigators who have IRB or Ethics 
Committee, and Sponsor approval. The Sponsor shall keep records to document the physical 
location of all investigational devices from shipment of investigational devices to the 
investigation sites until return or disposal. Devices are not transferable between Investigators 
unless prior approval is obtained from the Sponsor. Access to investigational devices shall be 
controlled and the investigational devices shall be used only in the clinical investigation and 
according to the Clinical Investigation Plan. 
The site Principal Investigator or an authorized designee shall keep records documenting the 
receipt, use, return and disposal of the investigational devices, which shall include 
1. the date of receipt, 
2. identification of each investigational device (batch number/serial number or unique 
code), 
3. the expiry date, if applicable, 
4. the date or dates of use, 
5. Subject identification, 
6. date on which the investigational device was returned/explanted from the Subject, if 
applicable, and 
7. the date of return of unused, expired or malfunctioning investigational devices, if 
applicable. 
An out-of-service product is defined as any implantable products (e.g. device, lead) removed or 
rendered inactive. Out-of-service product includes but is not limited to devices that do not 
function appropriately at implant and explanted product. Whenever possible, any out-of-service 
product should be returned to the Sponsor for analysis. In the event of a Subject death, every 
effort should also be made to return product to Mainstay Medical. 
10.5. Labeling  
All investigational devices will have a clinical investigation label, which will be visible on the 
pertinent shipping cartons and storage containers. The required labels or manuals will bear the 
following information: 
• 
Model and serial number of the device (the magnet does not have a serial number) 
• 
Name of the device and the address of Mainstay Medical as the manufacturer  
• 
Caution statement regarding investigational device 

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• 
All relevant contraindications, hazards, adverse effects, interfering substances or 
devices, warnings and precautions 
10.6. Data Monitoring Plan 
It is the responsibility of the Sponsor to ensure proper monitoring of the study per regulations. 
Appropriately trained Sponsor personnel or delegates appointed by the Sponsor will perform 
study monitoring at the investigation site in order to ensure that the study is conducted in 
accordance with the CIP, the signed Clinical Trial Agreement, and applicable regulatory 
requirements. The Sponsor must therefore be allowed access to the Subjects’ clinic and 
hospital records when so requested as per the consent form, Privacy Authorization (US only) 
and Clinical Trial Agreement. Procedures required in this CIP require source document 
verification for this study. A separate Monitoring Plan will detail levels of source verification for 
this study. 
Monitoring visits will be conducted periodically to assess study progress, the Investigator’s 
adherence to the CIP and regulatory compliance. This includes but is not limited to IRB/EC 
approval and review of the study, maintenance of records and reports, review of the consent 
process and review of source documents against Subject case report forms to ensure data 
points are correct and that adverse events are being reported. Monitors facilitate site regulatory 
and study compliance by identifying findings of non-compliance and communicating those 
findings along with recommendations for preventative/corrective actions to site personnel. 
Communication with the site personnel occurs during the visit and following the visit via a written 
follow-up letter. Monitors may work with study personnel to determine appropriate corrective 
action recommendations and to identify trends within the study or at a particular center. 
Frequency of monitoring visits will occur based on Subject enrollment, timing of the study visits, 
duration of the study, study compliance, findings from previous monitoring visits and any 
suspected inconsistency in data that requires investigation. All data used for a regulatory 
submission will be monitored against source documentation prior to the PMAA submission. 
All active sites will have a closure visit. A closure visit is a visit that occurs after a site’s last 
required follow-up visit. Closure visit activities may include source verification of the data and 
closure of any findings and/or study-related activities.  
Storage and accountability of investigational product used for this study will be assessed and 
monitored throughout the study at each site. 
10.7. Sponsor Responsibilities 
MML US Inc. (a subsidiary of Mainstay Medical Limited, Ireland) (“Mainstay”) is the Sponsor of 
this study, where a Sponsor is defined as an individual or organization taking the responsibility 
and liability for the intention or implementation of a clinical investigation. 
It is the responsibility of the Sponsor to ensure proper monitoring of the study and to see that all 
clinical requirements are met. In addition, Sponsor representatives may participate in the 
conduct of the Trial to the extent described in the following section on the role of the Sponsor 
representatives. In this study Sponsor representatives are not blinded to the study results, 
particularly since Sponsor representatives may be involved in device programming. Participation 
in the study will be limited to Sponsor personnel who are appropriately qualified and trained 
such as those personnel with an engineering, technical or nursing degree or equivalent training, 
or significant experience within the implantable device industry. All Sponsor personnel will be 
trained on the appropriate clinical study regulations and guidelines for medical device trials. 

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It is the responsibility of the Sponsor to ensure appropriate training of all individuals involved in 
the clinical Trial. This includes Investigators and other health care professionals at the 
investigational sites, Sponsor personnel, and contractors if applicable.  
10.8. Role of the Sponsor Representatives  
Sponsor personnel can provide technical support to the Investigator and other health care 
personnel (collectively HCP) as needed during implant, testing required by the CIP, and follow-
up visits. Support may include HCP training, addressing HCP questions, or providing 
clarifications to HCPs concerning the operation of Mainstay Medical equipment (including 
programmers and other support equipment) or the procedures and forms related to the CIP. 
At the request of the Investigator and while under the Investigator’s supervision, Sponsor 
personnel may operate equipment during implant or follow-up visits, assist with the conduct of 
testing specified in the CIP, and interact with the Subject to accomplish requested activities. 
Typical tasks may include: 
• 
Interrogating the device or programming device parameters to physician requested 
settings 
• 
Performing lead diagnostic testing using a programmer to obtain thresholds and 
impedance measurements 
• 
Clarifying device behavior, operation or diagnostic output as requested by the 
Investigator or other health care personnel 
• 
Assisting with the collection of study data from programmers and other equipment 
• 
Entering data on study worksheets as long as the responsible study Investigator verifies 
and signs the completed worksheet  
In addition, Sponsor representatives or designated technical personnel can perform certain 
activities to ensure study quality. These activities include: 
• 
Observing testing or medical procedures to provide information relevant to CIP 
compliance 
• 
Reviewing collected data and study documentation for completeness and accuracy 
At no point shall personnel from the Sponsor or CRO: 
• 
Practice medicine; 
• 
Discuss with the Subject the Subject’s diagnosis or recommend treatment; 
• 
Enter data into the eCRF; or 
• 
Discuss the Trial with the Subject. 
10.9. Clinical Investigators 
This study will be conducted in accordance with FDA Regulations 21CFR 812 and ISO 14155-
2011. A detailed list of the Investigators’ responsibilities can be found in 21CFR 812 and ISO 
14155-2011. The Investigator is responsible for conducting the study in accordance with the 
investigational plan, the latest version of the Declaration of Helsinki, the signed Investigator 
Agreement and other agreements, applicable laws and regulations, and any conditions of 
approval imposed by the reviewing IRB or Ethics Committee, and FDA or Competent Authority. 
To ensure compliance with the guidelines, the Sponsor, an independent body, or a regulatory 
agency may audit the study. By agreeing to this CIP, the Investigators and their institutions 
accept to allow monitoring, audits, IRB or Ethics Committee review, and regulatory inspections 
that are related to the study. They also agree to provide authorized individuals with access to 

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source data and documentation as well as the right to copy records, provided such activities do 
not violate Subject consent and Subject data confidentiality. 
The Investigator is responsible for protecting the rights, safety, and welfare of Subjects under 
the Investigator’s care, and for the control of devices under investigation. The Investigator is 
also responsible for ensuring that informed consent is obtained in accordance with this 
investigational plan, applicable regulatory requirements, and local IRB or Ethics Committee 
requirements. The Investigator or sub-Investigator may request the presence of Sponsor 
personnel at device-related procedures. 
A list of Investigators and institutions participating in this study will be available upon request.  
10.10. 
Investigator Selection  
In accordance with 21CFR 812 and ISO 14155-2011 the role of the site principal Investigator is 
to implement and manage the day-to-day conduct of the clinical investigation as well as ensure 
data integrity and the rights, safety and well-being of the Subjects involved in the clinical 
investigation. 
If the Sponsor contracts an institution to conduct the clinical investigation, the institution shall 
appoint an appropriately qualified person to be Site Principal Investigator. 
The Site Principal Investigator shall: 
• 
Be qualified by education, training and experience to assume responsibility for the 
proper conduct of the clinical investigation; evidence of such qualifications of the 
principal Investigator and key members of the investigation site team shall be provided 
to the Sponsor through up-to-date CVs or other relevant documentation 
• 
Be experienced in the field of application and trained in the use of the investigational 
device under consideration 
• 
Disclose potential conflicts of interest, including financial, that may interfere with the 
conduct of the clinical investigation or interpretation of results, and 
• 
Be knowledgeable with the method of obtaining informed consent. 
A Site Principal Investigator and any Sub-Investigator(s) must be experienced in and 
responsible for the following: 
• 
Subject well-being 
• 
Strict adherence to the Investigational CIP, which includes all testing requirements to 
provide for optimal safe and efficacious use of the investigational device 
• 
Return of explanted devices, if applicable 
• 
Providing the Subject with comprehensive information about the study and documenting 
Subject consent and data during the study 
• 
Addressing medical questions which might be asked, either by the Sponsor or by 
external Regulatory Agencies, during or after the study. 
• 
Notifying the Sponsor of any deviation from the Protocol with an explanation for the 
deviation. This notice shall be given as soon as possible, but in a timely manner after the 
deviation occurred.  
• 
The Investigator will ensure that any Adverse Event is reported according to Section 8.1. 
• 
Subject death during the study should be reported to the Sponsor as outlined in Section 
8.4. 
• 
Submission of death letters, notes, etc. if applicable 

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It is acceptable for the Site Principal Investigator to delegate one or more of the above functions 
to an associate or sub-Investigator. However, the Site Principal Investigator remains responsible 
for proper conduct of the study. The study is not transferable to other centers attended by the 
Investigator unless prior approval is obtained from the appropriate reviewing IRB or Ethics 
Committee, the Sponsor, and the appropriate regulatory authority (if applicable). 
10.11. 
Publication Policy 
A Publication Plan will be developed by the Sponsor and Investigators following approval of the 
Study, and for the duration of the Trial, the Publication Plan shall determine what information is 
to be submitted for publication, to which journal and/or meeting, and by whom. Publications 
shall have the order of authors as determined by the Publication Plan. 
Should presentation or publication be contemplated, the Sponsor shall be provided with copies 
of any abstracts, papers or manuscripts for review and approval within a reasonable period prior 
to submittal for publication or presentation. The Sponsor shall limit its review to a determination 
of whether Confidential Information is disclosed and shall not attempt to censor or in any way 
interfere with the presentation or publication beyond the extent necessary to protect Confidential 
Information or to allow the Sponsor to protect its rights in patentable or copyrightable material.  
Authorship of publications shall follow the recommendations of the International Committee of 
Medical Journal Editorsk, which may result in employees of the Sponsor being included as 
authors. 
10.12. 
Payment of Subjects 
Subjects will be reimbursed for reasonable transportation costs according to local institutional 
guidelines and regulatory requirements of up to US$550 (in local equivalent) in any calendar 
year. 
10.13. 
Maintaining Compliance 
The study will be conducted according to the stipulations of the FDA, the Declaration of Helsinki, 
ISO 14155-2011 and all other applicable regulations determined by country. 
10.13.1. Study Monitoring  
Monitoring will be performed during the study to ensure that compliance with the CIP and 
applicable regulations are maintained, that data are collected in a timely, accurate and complete 
manner and that the Investigator continues to have sufficient staff and facilities to conduct the 
study safely and effectively. 
Monitors are individuals who are designated to oversee the progress of a study. These 
individuals are appropriately trained and qualified to monitor the progress of a study. Monitors 
will be selected and assigned by Mainstay Medical.  
 
k  
http://www.icmje.org/ethical_1author.html 

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10.13.2. Review of Submitted Data 
In addition to the site monitoring visits the case report forms submitted by the Investigators will 
be reviewed. The following activities will occur: 
• 
All case report forms will be reviewed for completeness and accuracy upon receipt or 
after entry into the electronic data capture system 
• 
The Investigators and/or their clinical investigation representative and/or the Mainstay 
Medical designated personnel will be contacted regarding any missing or unclear data 
10.13.3. Securing Compliance  
In the event of repeated noncompliance, as determined by the Sponsor, a Sponsor or CRO 
representative will attempt to secure compliance by one or more actions: 
• 
Visiting the Investigator 
• 
Telephoning the Investigator 
• 
Corresponding with the Investigator 
If an Investigator is found to be repeatedly noncompliant with the signed agreement, the study 
CIP, applicable regulatory requirements, or any other conditions of the study, the Sponsor may, 
at its sole discretion, terminate the Investigator's participation in the study. In the event of 
termination of Investigator participation, study devices will be returned to the Sponsor unless 
this action would jeopardize the rights, safety, or welfare of the Subject. 
10.14. 
Study Completion 
The Sponsor will notify each Investigator of the completion or termination of the investigation or 
of the Investigator's participation in the study. At the Sponsor’s request, an Investigator will 
return any devices in his or her possession. The Investigator will provide a summary to the 
Sponsor and reviewing IRB or Ethics Committee of their investigation within 3 months of study 
termination. 
The Study Completion plan which details actions and responsibilities is shown in Table 5. 
10.15. 
Suspension or Premature Termination of the Trial 
The procedure to be followed as a result of suspension or premature termination of the Trial 
shall be in compliance with 21CFR 812 and ISO 14155. 
• 
The Sponsor may suspend or prematurely terminate either the clinical investigation in an 
individual investigation site or the entire clinical investigation for significant and documented 
reasons. 
• 
A principal Investigator, IRB or Ethics Committee, or regulatory authority may suspend or 
prematurely terminate participation in a clinical investigation at the investigational sites for 
which they are responsible. 
• 
If suspicion of an unacceptable risk to Subjects arises during the clinical investigation, or 
when so instructed by the IRB or ethics Committee, or regulatory authorities, the Sponsor 
shall suspend the clinical investigation while the risk is assessed. The Sponsor shall 
terminate the clinical investigation if an unacceptable risk is confirmed. 
• 
The Sponsor shall consider terminating or suspending the participation of a particular 
investigation site or Investigator in the clinical investigation if monitoring or auditing identifies 
serious or repeated deviations on the part of an Investigator. 

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If suspension or premature termination occurs, the terminating party shall justify its decision in 
writing and promptly inform the other parties with whom they are in direct communication. The 
principal Investigator and Sponsor shall keep each other informed of any communication 
received from either the IRB or Ethics Committee, or the relevant regulatory authority. 
If the Sponsor makes a decision to discontinue the study for any reason (e.g., slow enrollment, 
significant change in risk/benefit due to unanticipated adverse device effect, or other scenario), 
then the Sponsor will promptly inform all Investigators, IRBs or Ethics Committees, and relevant 
regulatory bodies along with detailed information on how enrolled Subjects should be managed 
thereafter. All Subjects enrolled in the Trial will continue to be followed according to the 
investigational plan unless the Sponsor notifies the investigational centers otherwise. 
An Investigator may also discontinue participation in the study with suitable written notice to the 
Sponsor. Should either of these events occur, the Investigator shall: 
• 
return all documents and devices to the Sponsor 
• 
provide a written statement as to why the premature termination has taken place 
• 
notify the IRB or Ethics Committee and the regulatory authority (if applicable) 
If suspension or premature termination occurs: 
1. the Sponsor shall remain responsible for providing resources to fulfill the obligations from 
the Clinical Investigation Plan and existing agreements for following up the Subjects enrolled 
in the clinical investigation;  
2. the principal Investigator or authorized designee shall promptly inform the enrolled Subjects 
at his/her investigation site, if appropriate; 
3. the Sponsor shall arrange, and each site shall cooperate, to remove all investigational 
devices from investigational sites, and 
4. the database from the clinical Trial at the time of termination shall be locked and made 
available for inspection by regulatory authorities or publication at a later date. 

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Table 5: Study Completion Plan 
Time of Completion 
After Subject reaches final study visit 
If study closed before Subject 
reaches final study visit . . . 
If Subject ends participation 
before final study visit . . .  
Note: All days are calendar days 
ReActiv8 
PMA 
Approval 
Decision to not 
pursue PMA 
Approval 
PMA Approval 
not Granted 
Study closed for 
safety reasons 
Study closed for 
other reasons 
Subject 
withdrawal 
Subject lost to 
follow-up 
Site must notify Subjects of the 
study completion plan within 
45 days 
45 days 
45 days 
45 days 
45 days 
n/a 
45 days 
Will Sponsor provide ongoing 
support? 
Yes 
No 
No 
No 
No 
No 
No 
IPG to be turned OFF (disabled)? 
No 
No* 
No* 
Yes 
No* 
No 
No 
Will external devices be collected? 
No 
No* 
No* 
Yes 
No* 
No 
No 
Explant required? 
No 
No 
No 
No* 
No 
No 
No 
Will Sponsor pay for explant 
procedure if needed? 
No 
Yes, for up to 
6 months 
Yes, for up to 
6 months 
Yes, for up to 6 
months 
Yes, for up to 6 
months  
Yes, for up to 
6 months  
Yes, for up to 
6 months  
What other surgical costs will 
Sponsor pay for? 
None 
None 
None 
None 
None 
None 
None 
Sponsor will pay for what type of 
clinic visits 
None 
One visit to  
1. inform of 
completion  
2. Turn off IPG 
3. collect 
externals 
One visit to  
1. inform of 
completion  
2. Turn off IPG  
3. collect 
externals 
One visit to  
1. inform of 
completion  
2. Turn off IPG  
3. collect 
externals 
One visit to  
1. inform of 
completion  
2. Turn off IPG  
3. collect 
externals 
One visit to  
1. inform of 
completion  
2. Turn off IPG  
3. collect 
externals 
One visit to  
1. inform of 
completion  
2. Turn off IPG  
3. collect 
externals 
How should symptoms related to 
the device be reported? 
Submit 
Complaint 
Submit 
Complaint 
Submit 
Complaint 
Submit 
Complaint 
Submit 
Complaint 
Submit 
Complaint 
Submit 
Complaint 
* 
Subject and Investigator to discuss 
 

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11. Administrative Data 
11.1. Name and Address of the Sponsor 
MML US Inc. 
6601 Shingle Creek Parkway 
Brooklyn Center, MN 55430 
MML US Inc. is a subsidiary of 
Mainstay Medical Limited 
Clonmel House 
Swords, K67F2K3 
County Dublin, 
Ireland 
Sponsor’s Contact: 
Ms. Diane Burnside 
Vice President Clinical Affairs 
diane.burnside@mainstay-medical.com 
Office: +1 763 270-5303 
Mobile +1 (763) 772-7637 
11.2. Investigators 
Each Investigational Site shall have a Site Principal Investigator. Subject to Sponsor approval, a 
Site Principal Investigator shall delegate some or all of the Subject interaction and data 
collection to one or more Sub-investigators. 
The overall Study Principal Investigator is: 
Chris Gilligan MD MBA 
Chief, Division of Pain Medicine 
Department of Anesthesia, Critical Care and Pain Medicine 
Brigham Pain Center 
Boylston Street, MA 
Dr. Gilligan was also Chairman of the DMC for the European Feasibility Study and the 
Chairman of the DMC for the ReActiv8-A Trial. 
11.3. Data Monitoring Committee 
The list of members, affiliations and roles and responsibilities of the DMC will be described in 
the DMC Charter, which will be stored as a part of the Trial Master File. 
11.4. Adjudication Committee 
The list of members, affiliations and roles and responsibilities of the Adjudication Committee will 
be described in a Charter, which will be stored as a part of the Trial Master File. 

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11.5. Clinical Research Organizations (CROs) 
Data collection will be performed with an electronic Case Report Form (eCRF). A CRO will 
manage the clinical database and will be responsible for randomization. The Sponsor will 
determine the data monitoring staff using the Sponsor’s and the CRO’s personnel. Subsidiary 
CROs may be used in certain countries. 
11.6. Statements of Compliance 
This clinical investigation shall be conducted in accordance with the ethical principles that have 
their origin in the Declaration of Helsinki. 
This clinical investigation shall be conducted compliance with FDA regulations, ISO 14155 and 
any regional or national regulations, as appropriate. 
The clinical investigation shall not begin until the required approval or favorable opinion from the 
FDA, IRB (or Ethics Committee), and any other regulatory body as appropriate and necessary in 
other countries. 
Any additional requirements imposed by the IRB, Ethics Committee, FDA or Competent 
Authority shall be followed, if appropriate. 

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Appendix 1: Acronyms and Definitions 
AE 
Adverse Event - any undesirable clinical occurrence that affects the health or safety 
of the Subject  
ALBP 
Axial Low Back Pain 
AMI 
Arthrogenic Muscle Inhibition – the physiological mechanism by which pain in a 
skeletal joint can inhibit activation of the muscles that surround or stabilize that joint 
BMI 
Body Mass Index 
CGI-I 
Clinical Global Impression – Global Improvement 
CIP 
Clinical Investigation Plan (this document). A document that state(s) the rationale, 
objectives, design and proposed analysis, methodology, monitoring, conduct and 
record-keeping of the clinical investigation. 
NOTE  The term “protocol” is synonymous with “CIP”. However, protocol has many 
different meanings, some not related to clinical investigation, and these can 
differ from country to country. Therefore, the term CIP is used in ISO 14155. 
CLBP 
Chronic Low Back Pain 
CRF 
Case Report Form(s) - set of printed, optical or electronic documents for each Subject 
on which information to be reported to the Sponsor is recorded, as required by the 
CIP (ISO 14155) 
CRO 
Contract Research Organization - person or organization contracted by the Sponsor 
to perform one or more of the Sponsor's clinical investigation-related duties and 
functions (ISO 14155) 
CV 
Curriculum vitae 
Deviation instance(s) of failure to follow, intentionally or unintentionally, the requirements of the 
CIP (ISO 14155). 
DD 
Device Deficiency. An inadequacy of a medical device with respect to its identity, 
quality, durability, reliability, safety or performance. 
DMC 
Data Monitoring Committee - independent committee that may be established by the 
Sponsor to assess, at intervals, the progress of the clinical investigation, the safety 
data or the critical performance endpoints and to recommend the Sponsor whether to 
continue, suspend, modify, or stop the clinical investigation (ISO 14155) 
DRG 
Dorsal Root Ganglion – is a cluster of nerve cell bodies located in the posterior region 
of the various vertebrae along the spine. It is adjacent to the dorsal nerve root, which 
exists as part of a pair of nerve roots exiting at each level of the spine. 
EC 
Ethics Committee - independent body whose responsibility it is to review clinical 
investigations in order to protect the rights, safety and well-being of human Subjects 
participating in a clinical investigation (ISO 14155 - NOTE For the purposes of 
ISO 14155, “ethics committee” is synonymous with “research ethics committee”, 
“independent ethics committee” or “institutional review board”. The regulatory 
requirements pertaining to ethics committees or similar institutions vary by country or 
region.) 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
EMG 
Electromyogram 
EQ-5D 
European Quality of Life Assessment 
FDA 
Food and Drug Administration 
HCP 
Health Care Personnel 
IB 
Investigator’s Brochure - compilation of the current clinical and non-clinical information 
on the investigational medical device(s), relevant to the clinical investigation 
(ISO 14155) 

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ICMJE 
International Committee of Medical Journal Editors 
IFU 
Instructions for Use 
IPG 
Implantable Pulse Generator 
IRB 
Institutional Review Board (equivalent to Ethics Committee) 
Labeling 
Per 21 CFR Part 801, 21 CFR Part 812, and 21 CFR Part 820, Section 201(m) defines 
‘labeling’ as: ‘all labels and other written, printed, or graphic matter (1) upon any article 
or any of its containers or wrappers, or (2) accompanying such article' at any time 
while a device is held for sale after shipment or delivery for shipment in interstate 
commerce.’ Labeling thus includes package labeling and accompanying manuals. 
Malfunction failure of an investigational medical device to perform in accordance with its intended 
purpose when used in accordance with the instructions for use or CIP (ISO 14155) 
MF 
Multifidus muscle of the lumbar spine (see also LM) 
Monitoring Act of overseeing the progress of a clinical investigation and to ensure that it is 
conducted, recorded, and reported in accordance with the CIP, written procedures, 
ISO 14155, and the applicable regulatory requirements (ISO 14155) 
NRS 
Numerical Rating Scale 
NSLBP 
Non-Specific Low Back Pain 
NSAID 
Non-Steroid Anti-Inflammatory. A class of drugs, sometimes used for low back pain. 
ODI 
Oswestry Disability Index 
OTC 
Over the Counter – refers to non-prescription medications 
PI 
Principal Investigator. A qualified physician who takes overall responsibility for 
conduct of the trial according to the protocol and regulations. 
PMA 
Pre-Market Approval 
PMCF 
Post-Market Clinical Follow Up 
PRO 
Patient Reported Outcome 
QOL 
Quality of Life 
Re-implant surgery 
A surgical procedure in which a new device is implanted to replace a device 
removed in a prior surgical procedure. 
Removal Surgery 
A surgical procedure in which at least one of either the leads or IPG is 
removed and not replaced with a device of the same type during the same surgical 
procedure 
Replacement Surgery  A surgical procedure that involves removal of one device component and 
implantation of a new device component of same type, e.g. lead, during a single 
surgical procedure 
Revision Surgery 
Surgical procedure performed on a currently implanted device, e.g. 
repositioning a dislodged lead  
SAE 
Serious Adverse Event. an adverse event that led to death, or led to serious 
deterioration in the health of the Subject, that either resulted in:  
1. a life-threatening illness or injury, or  
2. a permanent impairment of a body structure or a body function, or 
3. in-patient or prolonged hospitalization,  
4. congenital anomaly/birth defect, or  
5. medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function. 
Note: Planned hospitalization for a pre-existing condition or a procedure required by 
the protocol (e.g., the index implant procedure, or device replacement due to 
normal battery depletion), without serious deterioration in health, is not 
considered a serious adverse event. 
SAP 
Statistical Analysis Plan 

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SCS 
Spinal Cord Stimulator 
SGIC 
Subject Global Impression of Change 
Site PI 
Site Principal Investigator - qualified person responsible for conducting the clinical 
investigation at an investigation site (ISO 14155) 
Sponsor 
Individual or organization taking responsibility and liability for the initiation or 
implementation of a clinical investigation. For this Trial, it is Mainstay Medical Limited. 
Subject 
An individual who participates in a clinical investigation. A Subject can be either a 
healthy volunteer or a patient. (ISO 14155) 
TENS 
Transcutaneous Electrical Nerve Stimulation 
TSQ 
Treatment Satisfaction Questionnaire 
UADE 
Unanticipated Adverse Device Effect. Any serious adverse effect on health or safety 
or any life-threatening problem or death caused by or associated with, a device, if 
that effect, problem, or death was not previously identified in nature, severity, or 
degree of incidence in the investigational plan or application, or any other 
unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of Subjects. 
VAS 
Visual-Analogue Scale 

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Kent, P. M. & Keating, J. L. The epidemiology of low back pain in primary care. Chiropr. Osteopat. 13, 13 (2005). 
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