Investigational Device Exemption for Intrathoracic Nerve Stimulation
Phase: NA
Conditions: Postoperative Pain
Sponsor: The Cleveland Clinic

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Investigational Device Exemption Protocol for Intrathoracic 
Nerve Stimulation 
NCT04066374 
 
 
Sponsor: Usman Ahmad, M. D. 
Cleveland Clinic 
9500 Euclid Ave. J4-1 
Cleveland, OH  44195 
 
 

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Table of Contents 
Protocol Synopsis....................................................................................................................................................... 3 
Purpose ....................................................................................................................................................................... 5  
Background ................................................................................................................................................................ 5 
Report of Prior Investigations .................................................................................................................................... 5 
Alternative Therapies ................................................................................................................................................. 8 
Study Device and Technique Description .................................................................................................................. 8 
Number of patients/sites .......................................................................................................................................... 11 
Study Duration ......................................................................................................................................................... 11 
Patient Characteristics .............................................................................................................................................. 11 
Subject Recruitment and Informed Consent Process ............................................................................................... 11 
Primary Outcome Measures ..................................................................................................................................... 12 
Secondary Outcome Measures ................................................................................................................................. 12 
Hypothesis Testing ................................................................................................................................................... 12 
Data Collection and Analysis ................................................................................................................................... 12 
Pre-Procedure Screening: ......................................................................................................................................... 12 
Inpatient Days: ......................................................................................................................................................... 12 
Follow-up: ................................................................................................................................................................ 12 
Subject Withdrawal from the Study ......................................................................................................................... 13 
Subject Lost to Follow-up ........................................................................................................................................ 14 
Risk Assessment and Adverse Events ..................................................................................................................... 14 
Expected Benefits .................................................................................................................................................... 16 
Medical Monitor ...................................................................................................................................................... 16 
Monitoring ............................................................................................................................................................... 17 
IRB ........................................................................................................................................................................... 17 
Investigator Agreement ............................................................................................................................................ 18 
Device Charges ........................................................................................................................................................ 18 
Manufacturing Information ...................................................................................................................................... 18 
Labeling ................................................................................................................................................................... 18 
Reports ..................................................................................................................................................................... 19 
References ................................................................................................................................................................ 20 
 

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Protocol Synopsis 
Study Title 
Intrathoracic Nerve Stimulation 
Investigational Devices 
Medtronic Intellis, Spinal Cord Stimulation 
(SCS) 
Sponsor-Investigator 
Usman Ahmad, M. D. 
Assistant Professor of Surgery, CCLCM of 
CWRU 
Director, Thoracic Robotic Surgery Program 
Department of Thoracic & Cardiovascular 
Surgery  
Cleveland Clinic 
9500 Euclid Ave, J4-1, Cleveland, OH 44195  
216 444-1921  
AHMADU@ccf.org  
Study Purpose 
The purpose of this study is to conduct an early 
clinical evaluation of SCS, which will provide 
initial insight into the clinical safety and function 
of the device to determine if peripheral nerve 
stimulation (PNS) of the intercostal nerves using 
an electrical lead placed in the thoracic cavity is a 
safe and effective method of pain control after 
cardiothoracic surgery.  
Study Design 
Prospective, single-center, non-blinded, non-
randomized IDE study of the SCS for pain 
control after cardiothoracic surgery. 
Primary Endpoints 
a. Pain as measured by the visual analog scale 
b. Freedom from bleeding, infection, 
pneumothorax, arrhythmias 
Secondary Endpoints 
a. Morphine equivalents taken (both IV and PO) 
during the inpatient period 
b. Number of narcotics taken post discharge 
c. Pain control as measured by the McGill pain 
questionnaire. 
Patient Population 
Inclusion criteria:  
• Patients undergoing pulmonary surgery by 
open thoracotomy or thoracoscopy with or 
without robotic assistance. 
 
Exclusion criteria:  
• Woman who is pregnant, 
• Subjects who have an active systemic 
infection or are immunocompromised, 
• Subjects who will be exposed to 
diathermy or MRI, 

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• Subjects who have an electrically active 
implant, e.g., cardiac pacemaker, 
defibrillator, or neurostimulator, 
• Subjects who are on anticoagulation 
therapy that would preclude their ability 
to undergo the implant procedure, 
• Subjects less than 22 years of age, 
• Subjects at elevated risk of infection or 
bleeding, 
• Subjects unable to consent on their own, 
• Subjects with active infection, 
• Subjects with immunocompromised state, 
• Subjects with preoperative chest pain, 
• Subjects with pleural space infection or 
inflammatory process, 
• Subjects undergoing esophageal, tracheal, 
or gastric procedures, 
• Subjects undergoing pneumonectomy, 
• Subjects with an uncorrectable 
coagulopathy, 
• Subjects who are allergic or have shown 
hypersensitivity to any materials of the 
neurostimulation system which come in 
contact with the body. 
Number of Subjects 
10 
Number of Sites 
1 
Sample Size Justification 
The sample size is 10 subjects.  No formal sample 
size calculations were performed, as this study is 
not hypothesis driven. 
Study Hypothesis 
This is not a hypothesis driven study.  Descriptive 
summary statistics will be presented. 
Duration of Study 
Expected enrollment period is 6 months, follow-
up duration is up to 3 months (screening, 
procedure, POD 0 to discharge, and a follow-up 
visits or phone call by POD 14, 1 month and 3 
months. Total duration of the study is 1 year. 
Study Monitor 
Medical monitor will review all AEs.  Site 
monitoring will be performed internally by 
Cleveland Clinic Clinical Research Personnel.  
 
 
 

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Purpose 
The purpose of this study is to conduct an early clinical evaluation of Spinal Cord Stimulation (SCS), which will 
provide initial insight into the clinical safety and function of the device to determine if peripheral nerve 
stimulation (PNS) of the intercostal nerves using an electrical lead placed in the thoracic cavity is a safe and 
effective method of pain control after cardiothoracic surgery.  
Background 
Despite minimally invasive techniques in thoracic surgery, postoperative pain can still be an issue for patients. 
Achieving adequate pain control not only affects a patient’s short and long term quality of life but is also 
extremely important in preventing post-operative complications. Pain hinders with ambulating earlier and in 
performing pulmonary toilet hence increasing the risk of ensuing complications. While surgeons use multimodal 
approaches (e.g., epidural, regional anesthesia, NSAIDs, and opioids) to treat the postoperative pain, patients may 
not find relief in the acute period. Additionally, the use of opioids in the postoperative period can lead to chronic 
dependence and misuse. According to the Center for Disease Control, nearly 25% of patients chronically 
dependent on opioids started taking narcotics after they underwent a surgical procedure. Every day more than 115 
people a day die from narcotics, and costing the United States $78.5 billion dollars a year. To prevent the need for 
opioids and their associated side effects, we look beyond medications for postoperative pain control.  
The field of neuromodulation has been studying the effects of magnetic field and electrical current stimulation of 
different areas of the body to treat pain. While this has been shown to be effective for complex regional pain 
syndrome, low back pain, migraines and post herpetic neuralgia, there have not been studies applying the same 
concept to patients in the acute postoperative period. Our goal is to apply the same concept of peripheral nerve 
stimulation to treat post thoracic surgery pain and decrease the need for opioids for pain relief. 
The purpose of this IDE is to study the efficacy of peripheral nerve stimulation in treating post thoracic surgery 
pain and the safety of using these stimulation leads in the thoracic cavity. 
Report of Prior Investigations 
The Medtronic Intellis device is currently FDA approved for long term spinal cord stimulation to treat chronic 
low back pain (PMA# P840001/S344). The goal of our IDE study is to show the efficacy and safety of this device 
in an off-label use for peripheral nerve stimulation within the thoracic cavity. Specifically, we want to determine 
if using the Medtronic Intellis device in the thoracic cavity to stimulate the intercostal nerves is a safe and 
effective method of pain control in the acute post thoracic surgery period.  
Electrical Intercostal Nerve Stimulation 
Subcutaneous Electrical Intercostal Nerve Stimulation 
Listed below are two case reports detailing the use of electrical nerve stimulation directly over intercostal nerves, 
using subcutaneously tunneled electrical leads. Two patients with chronic thoracotomy pain underwent trials of 
medication and transcutaneous electrical nerve stimulation (TENS) without success1. After eight and ten-day trials 
of peripheral nerve stimulation (PNS) where significant pain control was reported for both patients (Visual 
Analog Scale 0/10 pain), both patients then underwent permanent St Jude’s Octrode and Quattrode lead 

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placement in the subcutaneous space over the area of pain1. Both patients reported significant improvement in 
quality of life and no longer required narcotics or antiepileptics for chronic pain1.  
The second case report involved a 13-year-old boy with chronic epigastric abdominal pain after undergoing a 
right nephrectomy for a malrotated right kidney. He underwent subcutaneous placement of the St. Jude permanent 
Octrode stimulator over the right lower intercostal nerves corresponding with D112. The patient noted significant 
acute pain control and within four months, he no longer required Fentanyl patches for pain control2. Ten months 
after placement, the patient was off all narcotic pain medications as well as gabapentin2.  
Both case reports did not mention any adverse events1-2. Listed below are the stimulators used and the associated 
device settings. 
Study 
Manufactur
er 
Stimula
tor 
Leads 
Accept
ed per 
Device 
Effecti
ve 
Curre
nt 
(mA) 
Effectiv
e Pulse 
Width 
(micros
ec) 
Effectiv
e 
Freque
ncy 
(Hz) 
Lead 
Conditio
n 
Tamimi et al 
(2009) 
Neuromodula
tion1 
St. Jude (was 
Advanced 
Neuromodul
ation 
Systems) 
Eon IPG 2 
2-3 
140-150 25-30 
St. Jude 
percutaneous 
leads 
4 or 8 
contacts 
8 contact span 
52 mm 
Quattrode/Oct
rode 
Chronic 
post 
thoracoto
my pain 
Johnson 
(2010) 
Ann R Coll 
Surg Engl2 
St. Jude (was 
Advanced 
Neuromodul
ation 
Systems) 
Eon IPG 2 
2-3 
500  
80 
St. Jude 
percutaneous 
lead 
8 contact 
60 mm span 
PN 3186 
Chronic 
intercost
al upper 
abdomin
al pain 
 
Transcutaneous Electrical Nerve Stimulation (TENS) of Intercostal Nerves 
TENS applies the same principles as electrical stimulation, but rather than placing a device directly over the 
nerves, TENS can be placed over the skin. Multiple randomized control trials have been conducted comparing 
TENS to other methods of pain control in the immediate post-operative period for thoracic surgery3-5.  
In a double blinded randomized placebo control trial, patients undergoing posterolateral thoracotomy were treated 
with TENS (n=60) or placebo (n=56) for five days following thoracic surgery3. Primary outcome was patient 
reported pain control as measured by the visual analog scale (VAS)3. Secondary outcomes were pulmonary 
function as measured by forced expiratory volume in one second (FEV1), forced vital capacity (FVC), partial 
arterial oxygen pressure (PaO2), partial arterial carbon dioxide pressure (PaCO2) 3. Additionally, the amount of 
pain medications administered were also compared3. At every time point, TENS was associated with superior pain 
control at rest and when coughing. This translated into a decreased amount of opioids taken by the TENS group 
compared to the control group3. Additionally, this translated to superior pulmonary function in the TENS group 
compared to the placebo control group3. There were no side effects in the TENS group, whereas the placebo 
control group had more nausea, vomiting and pruritus related to increased opioid use3. This same study was 

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replicated in another double blinded RCT involving fifty thoracic surgery patients in Italy. In addition to patient 
reported pain levels, opioid consumption and pulmonary function, the investigators also tracked inflammatory 
marker serum levels4. This trial also found that TENS was associated with improved patient reported pain (VAS), 
improved pulmonary function (FEV1), and decreased opioid use in the TENS group compared to the placebo 
group. The investigators also found that TENS was associated with lower serum levels of inflammatory markers 
IL-6, IL-10, and TNF-α4. It is unlikely that the lower serum levels of inflammatory markers is related to any 
difference in surgeries between the two groups, as both groups were well balanced in the procedures performed. 
The lower serum levels of cytokines in the TENS group was attributed in part to the TENS application4. However, 
the mechanism is not well understood. 
In a randomized trial comparing TENS (n=20) to paravertebral block (PVB, n=20), both were effective in treating 
post thoracic surgery pain5. The authors found that patients who received PVB experienced less pain both at rest 
and while coughing, which translated to less opioid use5. While there are concerns that PVB would cause 
hypotension, hemodynamic parameters did not differ among groups; however, FEV1/FVC was higher in the 
TENS group compared to the PVB group indicating superior recovery of pulmonary function in the TENS group5. 
TENS is able to provide some pain relief, however because of added subcutaneous tissue layers between the 
stimulation device and the peripheral nerves, the effects are not as magnified as peripheral nerve stimulation using 
implantable leads. 
Medtronic Intellis, Spinal Cord Stimulation (SCS)  
Long term implantable spinal cord stimulation devices have been well validated in treating chronic pain 
conditions including complex regional pain syndrome, low back pain, migraines and post herpetic neuralgia6-14. 
This technology was first developed in 1967 and FDA approved in 198914. SCS and PNS both employ alternating 
currents at specific frequencies to generate magnetic fields that stimulate nerves to provide pain relief. Exact 
mechanisms are not well understood, however likely involve gate theory13. Common complications of 
implantable SCS and PNS include infection (3.6 – 17.9%)15, bleeding, lead migration (9-25%)14-15, lack of 
efficacy (21%)15, or mechanical failures (3.6%)15 that may include failed connections in leads, and breakage of leads. 
The rates of these complications vary based on placement location, the duration of use, and the method of placement 
(e.g. ultrasound, fluoroscopic). Medtronic announced the FDA approval of their Intellis device September 18, 2017, 
which was designed to be smaller and overcome battery life and MRI compatibility limitations of other devices14. This 
device is currently being used by pain specialists and neurosurgeons to treat chronic low back pain. 
Off Label Use and Preliminary Data 
While this device is currently designed for long term placement in the body, our goal is to repurpose the technology for 
an acute period of time after thoracic surgery. After IRB approval (IRB 18-434 Intrathoracic Peripheral Nerve 
Stimulation Placement) we performed a pilot study showing that a similar flat paddle lead (St. Jude Lamitrode88) can be 
placed and removed safely intraoperatively without bleeding complications or injury to surrounding structures. Five 
patients underwent thoracic surgery under video thoracoscopic guidance. At the conclusion of the case as chest tubes 
were placed, we placed a paddle lead along the posterior chest wall perpendicular to the intercostal nerves under direct 
visualization. The leads were secured at two fixed points, one at the skin incision using a suture (the same manner as 
securing chest tubes), and the other fixed point under a short pleural bridge within the thoracic cavity. This fixation 
technique is designed to mitigate the risk of lead migration. Additionally, because this device will only be employed for 
as long as the chest tubes are in the chest (range 3-7 days), there should be lower risk of infection and bleeding/erosion 
compared to permanent SCS or PNS. 

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Alternative Therapies 
Current alternative therapies include systemic opioids, epidural, paravertebral blocks, intercostal nerve blocks, 
and transcutaneous electrical nerve stimulation. Despite the multitude of therapeutic options, patients still can 
have uncontrolled pain and discomfort. It is important to note that while analgesics instilled through an epidural 
catheter can provide effective pain control, the procedure is invasive, operator dependent and carries significant 
risks that can sometimes be prohibitive. More importantly this can only be used in a small subset of patients who 
do not have an infection and do not need anticoagulation. In addition, epidural catheters can only be placed in 
fully awake and cooperative patient in completely elective and planned settings. 
 Additionally, these alternatives are not without their own side effects. Beyond potentially addictive effects, 
opioids in the short-term cause nausea, vomiting, itching, constipation, respiratory depression, and hypotension. 
Epidurals and paravertebral block efficacy are user dependent on the person placing the device, which varies. 
Additionally, there is added operative time with both of these techniques. While TENS is helpful, its limited 
effectiveness has prevented widespread adoption in cardiothoracic surgery. 
Study Device and Technique Description 
Intraoperative 
At the conclusion of the thoracic operation while the lung is still deflated, when the chest tubes are about to be 
placed, a 1 cm wide pleural tunnel will be created with electrocautery in one intercostal space. The flat paddle 
lead will be slipped through the tunnel under direct visualization perpendicular to the intercostal nerves in the 
paraspinous space next to where the nerves exit the spine. The Blake drain will be placed in the posterior chest 
lateral to the paddle lead and the chest tube will be placed anterior to the lung per usual care. The anesthesiologist 
will then inflate the lung and we will confirm that the leads remain in place and that the chest is hemostatic. The 
lead, Blake drain, and chest tubes will then be secured at the skin in the usual manner and the incisions will be 
closed. Figure 1A-C. 
Depending on the patient’s anatomy and location of incisions, 2-3 paddle leads may be needed for appropriate 
coverage of all intercostal spaces. All leads will be placed in the same fashion. 
Figure 1A Flat paddle lead placed within the thoracic 
cavity at the conclusion of the procedure while the 
lung is still deflated. 
 
 
 
 
 
 

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Figure 1B A second point of fixation within a pleural 
tunnel created intraoperatively. The other point of 
fixation (not shown) is at the skin level. 
 
 
 
 
 
 
 
Figure 1C Flat paddle lead remains flat against the 
chest wall once the lung is inflated at the conclusion 
of the procedure. 
 
 
 
 
 
 

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 Figure 2: Internally placed paddle(s) connected to 
externally placed pulse generator 
 
 
Postoperative 
After the patient is taken from the operating room to recovery, a postoperative chest x-ray (CXR) will be obtained 
as part of standard clinical care. This will confirm that the paddle lead, Blake drain, and chest tubes remain in the 
correct orientation after patient transport to postoperative recovery. The device will be tested and programmed in 
the immediate postoperative period once the patient has sufficiently recovered from anesthesia. The patient will 
be able to toggle between different stimulation programs based on their preference for pain control during the 
trial. During each day of the trial, the patient will have the opportunity to have new programs added as needed. 
The patient will be able to arrest stimulation at any time if it causes discomfort.  
Daily CXR will be obtained as part of the usual postoperative care. On CXR, it is standard routine to evaluate 
heart and lung fields as well as chest tube locations. Additionally, the investigators will evaluate the paddle lead 
location on CXR as well.  
A clinical programmer will adjust the device settings as needed for patient comfort. Patient reported pain level as 
measured by the VAS will be recorded every four hours as per standard nursing protocol during the inpatient stay. 
These will be documented in the patient’s chart and recorded by the research personnel. 
Removal 
The device must be and will be removed before the patient is discharged from the hospital. The average length of 
a hospital stay is 3-4 days; however, depending on the subject’s condition, it may be longer than 7 days. Once it is 
deemed that the patient no longer requires the chest tubes, the paddle lead will be removed the same way a drain 
or chest tube is removed. The paddle lead will be removed before the chest tube is removed to mitigate risk of 
pneumothorax. The stitch securing the paddle lead to the skin will be cut and the patient will be asked to take in a 
deep breath and hold it. The paddle lead will then be swiftly and smoothly removed from the chest cavity and an 

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occlusive Vaseline gauze will be placed over the skin incision where the paddle lead had exited. A CXR after 
paddle lead and chest tube removal will be obtained confirming that there is no pneumothorax or hemothorax as a 
result of lead removal.   
Rescue Medications - Fentanyl PCA 20 mcg q 10 min up to 6 doses per hour until they have reliable oral intake.  
Then 5-10 mg of oxycodone q 4-6 hours can be utilized per clinical guideline when subjects require rescue 
medications.  Tylenol is given as a standard clinical protocol.  Type and number of narcotics medications taken 
will be collected and reported.  
Number of patients/sites   
10 patients to be recruited at one site, the Cleveland Clinic Main Campus. 
Study Duration 
Expected enrollment period is 6 months, follow-up duration is up to 3 months, and total duration of the study is 1 
year. 
Patient Characteristics 
Inclusion criteria:  
• 
Patients undergoing pulmonary surgery by open thoracotomy or thoracoscopy with or without robotic 
assistance. 
 
Exclusion criteria:  
• 
Woman who is pregnant, 
• 
Subjects who have an active systemic infection or are immunocompromised, 
• 
Subjects who will be exposed to diathermy or MRI, 
• 
Subjects who have an electrically active implant, e.g., cardiac pacemaker, defibrillator, or 
neurostimulator, 
• 
Subjects who are on anticoagulation therapy that would preclude their ability to undergo the implant 
procedure, 
• 
Subjects less than 22 years of age, 
• 
Subjects at elevated risk of infection or bleeding, 
• 
Subjects unable to consent on their own, 
• 
Subjects with active infection, 
• 
Subjects with immunocompromised state, 
• 
Subjects with preoperative chest pain, 
• 
Subjects with pleural space infection or inflammatory process, 
• 
Subjects undergoing esophageal, tracheal, or gastric procedures, 
• 
Subjects undergoing pneumonectomy, 
• 
Subjects with an uncorrectable coagulopathy, 
• 
Subjects who are allergic or have shown hypersensitivity to any materials of the neurostimulation system 
which come in contact with the body. 
 
Subject Recruitment and Informed Consent Process 
All patients must provide informed consent prior to any study related procedures being performed.   Patients are 
assessed for acceptability into the study by the study investigators.  If they meet the inclusion criteria, the 

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possibility of the utilization of pain control by the neuro-stim IDE will be discussed in hospital exam rooms or the 
outpatient clinic. 
   
The investigator will review the patient’s history, physical examination, and radiographic studies prior to 
obtaining informed consent.  An IRB approved informed consent form will be obtained from the patient after the 
purposes of the study, the risks, expected discomforts, and potential benefits have been explained.  Because of the 
need for emergency or urgent operations, the informed consent form may be signed by the patient or by a family 
member / proxy.  Copies of the informed consent will be included in the study records.  Another copy will be 
given to the patient for their records. 
Primary Outcome Measures 
Primary outcome:  
a. Pain as measured by the visual analog scale 
b. Freedom from bleeding, infection, pneumothorax, arrhythmias 
Secondary Outcome Measures 
Secondary outcome:  
a. Morphine equivalents taken (both IV and PO) during the inpatient period 
b. Number of narcotics taken post discharge 
c. Pain control as measured by the McGill pain questionnaire. 
Hypothesis Testing 
This is not a hypothesis driven study. Descriptive summary statistics will be presented for all data points. 
 
Data Collection and Analysis 
The data will be collected in a 21CFR part 11 compliant database, REDCap Cloud. No statistical analysis beyond 
counts and frequencies will be required. The results of this study will be described in a case report format. 
Pre-Procedure Screening: 
History and physical will be performed to ensure that the subjects meet the inclusion criteria and do not meet any 
of the exclusion criteria of the study.  Women of child-bearing potential, the pregnancy test will be performed 
prior to the procedure. 
Subjects will be asked to answer Mc Gill Pain Questionnaire as a baseline assessment. 
Inpatient Days: 
Visual analog pain assessment and morphine equivalence will be collected.  Daily chest X-ray will be taken and 
findings will be collected until discharge. 
Follow-up: 
Subject will return at 2 weeks, 1 month, and at 3 months for pain assessment.  If subjects are unable to return, a 
phone visit will be performed to collect pain assessment and AE assessment. 
 

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Follow-up Schedule Table: 
Procedures 
Screening 
Intraoperative 
POD 
0 
POD 1 to 
Day of 
Discharge 
First 
outpatient 
postoperative 
visit  
(POD 7 -14) 
1 month 
(POD 21 
– 31)  
3 months 
( POD 45 
– 90) 
McGill Pain 
Questionnaire 
X 
 
 
 
X 
X 
X 
Peripheral 
nerve 
stimulator 
placement 
 
X 
 
 
 
 
 
Peripheral 
nerve 
stimulator 
activation 
 
 
X 
X 
 
 
 
Peripheral 
nerve 
stimulator 
removal 
 
 
 
X 
 
 
 
Visual Analog 
Scale Pain 
assessment 
 
 
X 
X 
X 
X 
X 
Chest X-ray 
 
 
X 
X  
(daily until 
dc) 
 
 
 
Number of 
Narcotics 
Taken 
 
 
X 
X 
X 
X 
X 
Assessment of 
AE 
 
X 
X 
X 
X 
X 
X 
Subject Withdrawal from the Study 
A subject may withdraw from the study at any time and should notify the investigator in this event.  The 
investigator may also withdraw the subject from the clinical study at any time based on his medical judgment.  

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Subject Lost to Follow-up 
A subject will be considered lost to follow-up and terminated from the study once they have missed two 
consecutive appointments without contacts and three attempted contacts are unanswered (it must include a contact 
with certified letter). 
Risk Assessment and Adverse Events 
Definition of Adverse Events (AE): 
An adverse event is an untoward medical occurrence or exacerbation of an existing medical condition subsequent 
to the experimental therapy.  For this study, adverse events are rated in the following ways: 
• 
Anticipated (anticipated, not anticipated) 
• 
Device and procedure relationships (unrelated, possibly related, or related) 
 
Adverse events will be categorized as either serious or non-serious.  A Serious Adverse Event (SAE) is an event 
that meets at least one of the following: 
• 
Is fatal 
• 
Is life-threatening 
• 
Results in persistent or significant disability/incapacity 
• 
Results in permanent impairment of a body function or permanent damage to a body structure 
• 
Results in hospitalization or prolongs a hospitalization 
• 
Necessitates medical or surgical intervention to preclude permanent impairment of a body function or 
permanent damage to a body structure 
 
Definition of an Unanticipated Adverse Device Effect (UADE) : 
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 (including a supplementary application), or any other 
unanticipated serious problem associated with the device that relates to the rights, safety, or welfare of subjects. 
 
Risks and Risk Mitigations Strategy: 
The purpose of this study is to assess the safety of an electrical stimulation lead in the thoracic cavity. Summary 
of some of the known risks is identified below; however, there may be risks that are not known or unforeseen at 
this time.  The severity of any particular event may vary depending on the subject’s pre-existing conditions or 
comorbidities.  AEs will be collected and classified as device-related, procedure-related or unrelated; events that 
are related to pre-existing condition are not considered as AEs.  
  
Adverse events associated with the application of this procedure may include, but are not limited to, the following 
(the severity of any particular event may vary depending on the patient’s pre-existing conditions or comorbidity): 
 
Possible AE 
Likelihood 
Severity 
Risk Mitigation 
Strategy 
Discomfort 
Less likely 
Mild 
Very little discomfort is 
expected. Subjects will 
have traditional pain 

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management methods 
available to them as well. 
Bleeding 
Rare 
Mild to moderate 
It is unlikely that that this 
device will cause 
bleeding.  
If there is bleeding 
related to the device, then 
the treatment may range 
from watchful waiting to 
blood transfusion and to 
reoperation. 
Infection 
Rare 
Mild to moderate 
It is unlikely that this 
device will cause 
infection.  
If there is infection 
related to the device, then 
the device will be 
removed. The treatment 
may range from 
intravenous antibiotics to 
reoperation. 
Mechanical failure of the 
lead (lead displacement, 
lead fracture, wire 
fracture) 
Rare 
Mild to moderate 
It unlikely that this device 
will have mechanical 
failure.  
If there is lead/wire 
fracture then this would 
require reoperation.  If 
leads are displaced then 
the treatment can range 
from watchful waiting to 
device removal.  
Device malfunction 
Rare 
Mild 
It is unlikely that the 
device will malfunction. 
If the device is not 
functional, then a new 
stimulator will be 
attached to the stimulator 
leads. If there is not a 
functional stimulator 
available, then the leads 
will be removed. 
Arrhythmia 
Rare 
Mild to moderate 
It is unlikely that there 
will be arrhythmias 
caused by the electrical 
leads. The patients will 
be attached to the cardiac 
monitors during the 
postoperative stay, as per 
standard care. If the 
patient develops an 

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arrhythmia, then the 
stimulator will be turned 
off. If this resolves the 
arrhythmia, then it will be 
noted that the device 
likely caused the 
arrhythmia. If the 
arrhythmia persists 
despite the device being 
turned off, then it is 
unlikely that the device is 
the cause of the 
arrhythmia. If there is 
suspicion that the lead 
itself, even while turned 
off, is responsible for an 
arrhythmia, then the lead 
will be removed. 
Pneumothorax 
Rare 
Mild to moderate 
It is unlikely that a 
patient will have a 
pneumothorax after lead 
removal. To mitigate this 
risk, the lead will be 
removed prior to chest 
tube removal. Treatment 
may range from 
nonoperative 
management to chest tube 
placement. 
 
All AEs will be captured via electronic data capture (EDC) system. 
 
Expected Benefits 
If the device works the way we expect it to, then the patient should experience pain relief and potentially some 
paresthesia in the distribution of the intercostal nerves affected. Effective pain control will allow the patient to 
mobilize earlier in the hospital stay and perform pulmonary toilet functions more effectively without the side 
effects of systemic opioids or epidurals. 
 
Medical Monitor 
To ensure consistent and accurate AE reporting and classification, an independent medical monitor will be 
established. The medical monitor will assess all AEs captured by the study coordinator(s).  
 

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Monitoring  
Study monitoring will be performed by experienced and appropriately trained personnel appointed by the sponsor-
investigator to ensure that the investigation is conducted accordance with the FDA IDE regulations.  Monitoring will be 
conducted by the independent monitor in CCF HVI Research Department. 
 
HVI (Heart and Vascular Institute) Research Department 
Cleveland Clinic Foundation  
9500 Euclid Ave. 
Cleveland, OH  44195 
 
 
On-site monitoring will occur at regular intervals throughout the duration of the trial, and monitor visit with summary of 
findings will be outlined in monitoring report. 
 
Monitoring activities will include: 
• 
Study Initiation visit 
• 
Review of training and delegation of authority log  
• 
Review of FDA/IRB approval letters and correspondences 
• 
Review of informed consent to ensure: 
o That the subject signed and dated the informed consent form for him/herself 
o A valid and effective version (reviewed and approved by the IRB) of the consent form was 
used 
o That the informed consent process was appropriately documented 
• 
Confirmation that the study staff is conducting the study in compliance with the protocol approved by 
the IRB. 
• 
Source Document Verification (i.e., review all subjects’ charts for: study eligibility, primary and 
secondary endpoints data, and that the protocol specific source documents are on file) 
• 
Ensuring the data reported on the eCRF is consistent with the source documentation 
• 
Review of outstanding queries on the eCRF 
• 
Review of all subject research records to ensure the following: 
o All AEs and SAEs have been reported including any abnormal exam findings determined to 
be clinically significant; 
o AEs have been reviewed, attribution has been assigned and signed by investigator in a timely 
manner; 
o EAEs and SAEs have been submitted to the IRB and FDA per IRB/FDA reporting criteria; 
and 
o All deaths have been reported appropriately 
• 
Ensuring any protocol deviation that meets reporting requirements has been reported to the IRB as well 
as reported in eCRF 
• 
Ensuring investigational products have been properly handled 
• 
Verification of device used  
• 
Study termination/closure visit 
 
IRB 
The protocol shall be evaluated and approved by the Institutional Review Board at the Cleveland Clinic Foundation prior 
to proceeding with the study. 

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Institutional Review Board 
Alan Lichtin, MD – IRB Chairman 
Cleveland Clinic Foundation 
9500 Euclid Avenue, OS 1 
Cleveland, OH 44195 
 
(216) 444-5848 
 
Investigator Agreement 
Dr. Usman Ahmad, as a study Sponsor and P.I. will certify all participating investigators will sign the investigator 
agreement and no investigator will be added until the investigator agreement is signed in accordance with 21 CFR 
812.29(b)(5). 
 
Investigator responsibilities include, but not limited to: 
• 
Conducting the study in accordance with the investigational plan, signed agreement and applicable regulations 
protecting the rights and safety of study subjects 
• 
Informing all subjects that the device being utilized is for investigational purposes, and ensuring that the 
requirements relating to obtaining informed consent and IRB approval are met 
• 
Ensuring that IRB approval is secured prior to staring the study and ensuring continuing review and approval as 
required throughout the investigation 
• 
Ensuring and supervise all associates, colleagues, and employees assisting the conduct of the study are informed 
about their obligations, are adequately qualified and trained, and meet their commitments 
• 
Maintaining adequate and accurate records and ensuring those records are available for inspection at any time 
• 
Ensuring that conducting the study does not give rise to conflict of interest 
• 
Controlling of all investigational devices 
 
 
Device Charges 
The device will be charged at the same amount charged by the manufacturers of the devices to the hospital.  The devices 
that are used as part of their clinical care is billed to the subject and or his/her medical insurance. 
 
Manufacturing Information 
The Medtronic Intellis Spinal Cord Stimulation (SCS) is manufactured, sterilized and packaged by Medtronic. 
We will not be tampering or adjusting the packaging in any way. 
 
Labeling 
Sample Label: 

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Reports 
Deviation from the Investigational Plan:  The sponsor-investigator will notify the reviewing IRB and FDA of 
any deviation from the investigational plan to protect the life of physical well-being of a subject in an emergency.  
The notice will be provided as soon as possible but no later than 5 working days after the emergency occurred.  If 
the change or deviation may affect the scientific soundness of the investigational plan or the rights, safety or 
welfare of the subject, the sponsor will obtain prior IRB and FDA approval for deviation by submitting an IDE 
supplement.   
UADE:  The sponsor-investigator will report the results of an evaluation of an unanticipated adverse device effect 
to FDA and IRB within 10 working days after the sponsor-investigator first receives notice of the device adverse 
effect. 
Withdrawal of IRB approval:  The sponsor-investigator will notify FDA of the withdrawal of IRB approval or 
any part of the investigation within 5 working days of receipt of withdrawal of approval. 
Progress report or annual reports:  The sponsor will provide progress reports to the reviewing IRB and to the 
FDA.  In addition, the sponsor will submit interim progress reports summarizing the outcomes will be provided 
after the initial 5 subjects return for their first post-operative follow-up visit to the IRB and FDA. 
Recall and device dispositions:  The sponsor-investigator will notify FDA and reviewing IRB of any request that 
a sponsor-investigator return, repair, or dispose of any unit of an investigational device.  The notice will be made 
within 30 days after the request is made and will state why the request was made. 

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Final report: The sponsor-investigator will notify FDA and reviewing IRB within 30 working days of the 
completion or termination of the study.  The sponsor-investigator will also submit a final report to FDA and 
reviewing IRB within 6 months after the completion or termination of the study.   
Failure to obtain informed consent:  The sponsor-investigator will submit a report of the use of a device 
without first obtaining informed consent.  The report will be made to the FDA within 5 working days after receipt 
of notice of such use. 
Other reports:  The sponsor-investigator will provide accurate, complete, and current information about any 
aspect of the investigation upon request from the reviewing IRB or FDA 
 
 
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