A Prospective, Multicenter Study of REflux Management With the LINX® System for Gastroesophageal REFlux Disease After Laparoscopic Sleeve Gastrectomy
Phase: NA
Conditions: GERD, Gastroesophageal Reflux Disease
Sponsor: Torax Medical Incorporated

 
Doc. No. 4600 Rev. 5 
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Effective Date: 25July2018 
 
 
RELIEF Study  
A Prospective, Multicenter Study of Reflux Management  
with the LINX® System for Gastroesophageal 
REFlux Disease after Laparoscopic Sleeve Gastrectomy 
 
PROTOCOL 
NUMBER 
4600 Rev 5 
SPONSOR 
 
Torax Medical, Inc. 
4188 Lexington Avenue North 
Shoreview, MN 55126 
Phone:  651-361-8900 
Fax:  651-361-8910 
 
INVESTIGATOR’S 
SIGNATURE 
 
I have received and reviewed the above 
mentioned protocol and revision.  I agree to 
personally conduct or supervise the described 
clinical study in accordance with the protocol at 
my institution.   
 
 
 
 
 
 
 
 
Principal Investigator’s Printed Name 
 
 
 
 
 
 
 
 
 
Principal Investigator’s Signature 
 
 
 
 
 
 
 
 
Date 
 
 

 
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TABLE OF CONTENTS 
 
1.0 
BACKGROUND ..................................................................................................................................... 6 
2.0 
THE LINX REFLUX MANAGEMENT SYSTEM ................................................................................ 6 
2.1 
DEVICE DESCRIPTION .................................................................................................................. 6 
2.2 
REGULATORY HISTORY................................................................................................................ 6 
3.0 
STUDY PURPOSE AND OBJECTIVE ................................................................................................. 8 
4.0 
STUDY RATIONALE ............................................................................................................................ 8 
5.0 
STUDY DESIGN .................................................................................................................................... 9 
5.1 
ASSESSMENT OF SAFETY .............................................................................................................. 9 
5.2 
ASSESSMENT OF EFFICACY ........................................................................................................... 9 
6.0 
SELECTION AND WITHDRAWAL OF SUBJECTS .......................................................................... 9 
6.1 
INCLUSION CRITERIA ................................................................................................................... 9 
6.2 
EXCLUSION CRITERIA ................................................................................................................ 10 
7.0 
STUDY SCHEDULE AND ASSSEMENTS ......................................................................................... 11 
8.0 
SUBJECT FLOW CHART .................................................................................................................. 15 
9.0 
RISK ANALYSIS ................................................................................................................................. 15 
9.1 
POTENTIAL RISKS ...................................................................................................................... 15 
9.2 
POTENTIAL BENEFITS................................................................................................................. 16 
10.0 
STATISTICAL PLAN .......................................................................................................................... 16 
10.1 
EFFICACY .................................................................................................................................. 16 
10.1.1 
Esophageal Acid Exposure .......................................................................................... 16 
10.1.2 
Quality of LIFe ............................................................................................................ 16 
10.1.3 
Use of PPis ................................................................................................................. 16 
10.2 
SAFETY 16 
10.3 
ADDITIONAL ANALYSES ............................................................................................................ 17 
10.4 
SUBJECT POPULATION FOR ANALYSIS ......................................................................................... 17 
11.0 
STUDY PROCEDURES AND MANAGEMENT ................................................................................ 17 
11.1 
CLINICAL STUDY REGISTRATION ................................................................................................ 17 
11.2 
STUDY CENTER SELECTION AND PARTICIPATION ........................................................................ 17 
11.3 
INFORMED CONSENT .................................................................................................................. 18 
11.4 
INSTITUTIONAL REVIEW BOARD ................................................................................................. 18 
11.5 
SITE ACTIVATION ...................................................................................................................... 18 
11.6 
STANDARD OF CARE .................................................................................................................. 18 
11.7 
SCREENING/ENROLLMENT.......................................................................................................... 19 
11.8 
DEVICE TRACKING .................................................................................................................... 19 
11.9 
ADVERSE EVENT REPORTING .................................................................................................. 19 
11.10 
SUBJECT COMPLETION AND WITHDRAWAL ................................................................................. 20 
12.0 
ROLE AND RESPONSIBILITIES ...................................................................................................... 21 
12.1 
INVESTIGATOR........................................................................................................................... 21 
12.2 
STUDY COORDINATOR ............................................................................................................... 21 
13.0 
STUDY CENTER DOCUMENTATION ............................................................................................. 21 
14.0 
STUDY PATIENT RECRUITMENT AND RETENTION PLAN ...................................................... 22 
15.0 
DATA HANDLING AND RECORD KEEPING ................................................................................. 22 
15.1 
CONFIDENTIALITY ..................................................................................................................... 22 
15.2 
SOURCE DOCUMENTS ................................................................................................................ 23 
15.3 
CASE REPORT FORMS ................................................................................................................ 23 
15.4 
RECORDS RETENTION ................................................................................................................ 23 

 
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16.0 
QUALITY ASSURANCE AND QUALITY CONTROL ..................................................................... 23 
17.0 
PUBLICATION PLAN ......................................................................................................................... 24 
 
 
LISTING OF TABLES 
Table 1:  Schedule of Data Collection and Follow-Up Windows ............................................... 12 
Table 2:  Completion of Questionnaires and GERD Medication ................................................ 13 
Table 3:  Planned Assessments .................................................................................................. 13 
Table 4:  Follow-up Windows ................................................................................................... 14 
 
 
APPENDICES 
Appendix A:  LINX Instructions for Use (IFU) 
Appendix B: Guidelines for Testing 
• Guidelines for pH testing 
• Guidelines for Endoscopy testing 
• Guidelines for X-Ray testing 
• Guidelines for Barium Swallow testing 
• Guidelines for Manometry/Motility testing 
Appendix C:  Informed Consent (Template) 
Appendix D:  Case Report Forms (CRFs) 
 
 

 
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Protocol Synopsis 
Protocol ID 4600 
Sponsor 
Torax Medical, Inc. 
4188 Lexington Ave. North 
Shoreview, MN 55126 
Tel:  (651) 361-8900  
Fax: (651)361-8910 
Study Title 
RELIEF Study:  A Prospective, Multicenter Study of Reflux Management with the 
LINX® System for Gastroesophageal Reflux Disease after Laparoscopic Sleeve 
Gastrectomy  
Study Device 
The LINX® Reflux Management System (LINX) 
Indication 
The LINX® Reflux Management System is a laparoscopic, fundic-sparing anti-reflux 
procedure indicated for patients diagnosed with Gastroesophageal Reflux Disease 
(GERD) as defined by abnormal pH testing, and who are seeking an alternative to 
continuous acid suppression therapy (i.e. proton pump inhibitors or equivalent) in the 
management of their GERD. 
FDA Approval 
March 22, 2012 
Study Design 
An observational, multicenter, single-arm study with prospective enrollment.   
Purpose 
To evaluate the safety and efficacy of LINX for its approved indication in patients 
who have had prior gastric surgery, specifically, laparoscopic sleeve gastrectomy 
(LSG). 
Objective 
To confirm safety and efficacy after LSG in patients indicated for LINX is similar to 
the outcomes that formed the basis for Premarket Approval (PMA) to support 
modification of the current labeling with a statement that prior gastric surgery with 
LSG has been evaluated for safety and efficacy. 
Number of Subjects 
Up to 30 subjects 
Study Centers 
Up to 12 implanting sites in the U.S. 
Study Duration 
36 months (24-month enrollment period + 12-month follow-up period) 
Evaluation of Safety 
Rate of serious device and procedure related adverse events assessed by reporting all 
adverse events and by estimating the rate of serious device and procedure related 
adverse events through 12 months post implantation.  Safety will also be evaluated 
by endoscopy to assess the mucosa and abdominal/chest X-ray evaluations to verify 
device location at 12 months post implantation. 
Evaluation of 
Efficacy  
Percentage of subjects reporting at the 12-month follow-up: 
• 
Normalization of total distal acid exposure (% total time pH<4) or at least 
50% reduction in total distal acid exposure compared to baseline 
• 
At least 50% reduction in total GERD-HRQL score compared to baseline (off 
PPIs) 
• 
At least 50% reduction in average daily PPI dosage compared to baseline 
Study Management  
Torax Medical Inc. or Designate 
 

 
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Schedule of Data Collection    
X=All study subjects 
1Screening/baseline GERD-HRQL questionnaire is completed twice:  once on GERD medication and once off GERD 
medications for at least 7 days, with the exception of antacids which can be taken up until the morning of assessment. 
2 Completed/conducted off GERD medications for at least 7 days, with the exception of antacids which can be taken up 
until the morning of assessment. 
3Testing performed after implant and prior to discharge or within 7 days of implant, whichever occurs first. 
Screening/ Baseline 
Implant /Discharge 
2-week Post-Operative Visit (Day 7 – Day 21) 
3 months  (Day 76 – Day 104) 
6 months  (Day 150 – Day 210) 
12-month Visit  (Day 305 – Day 425) 
 
 
 
Data Collected 
X 
 
 
 
 
 
Demographics (gender, race) 
X 
 
 
 
 
X 
Height and Weight  
X 
 
 
 
 
X 
Medical History  
 
X 
 
 
 
 
Implant Procedure and Discharge Data 
X 
 
 
 
 
X 
Endoscopy (LA Grade Classification) 
X 
 
 
 
 
X 
Manometry/Motility 
X 
X3 
 
 
 
X 
Barium Esophagram  
 
X3 
 
 
 
X 
Upright Bi-Planar X-Rays (AP and Lateral) 
X 
 
 
X 
X 
X 
GERD Medications 
X1 
 
 
X2 
X2 
X2 
GERD-HRQL  
X2 
 
 
X2 
X2 
X2 
Foregut Symptom Questionnaire 
X2 
 
 
 
 
X2 
Esophageal pH Measurements (off PPIs) 
 
X 
X 
X 
X 
X 
Device and/or Procedure Adverse Events  

 
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1.0 
BACKGROUND  
There are several types of surgical weight loss procedures. The Laparoscopic Sleeve 
Gastrectomy (LSG) is a restrictive weight loss procedure that is performed by removing 
about 75% of stomach. It is estimated that as many as 84.1% of the subjects with pre-
existing Gastroesophageal Reflux Disease (GERD) that undergo the LSG can continue to 
have chronic GERD symptoms1 and as many as 8.4% of patients that did not have pre-
existing GERD can develop new onset GERD symptoms. The traditional surgical method 
of using the patients’ anatomy (fundus) to perform a fundoplication is no longer an option 
for these patients and the treatment alternatives for patients experiencing GERD symptoms 
after LSG are few. The Roux-en-Y Gastric bypass (RYGB) has been recommended as a 
conversion procedure for those who develop or continue to have reflux after LSG. 
However, the LINX Reflux Management System (LINX) has been considered as an 
alternative and less invasive option that may potentially have fewer complications 
compared to RYGB.  
 
2.0 
THE LINX REFLUX MANAGEMENT SYSTEM 
2.1 
DEVICE DESCRIPTION 
The LINX® Reflux Management System is a laparoscopic, fundic-sparing anti-
reflux procedure indicated for patients diagnosed with Gastroesophageal Reflux 
Disease (GERD) as defined by abnormal pH testing, and who are seeking an 
alternative to continuous acid suppression therapy (i.e. proton pump inhibitors or 
equivalent) in the management of their GERD.  The LINX device is a permanent 
implant placed at the area of the lower esophageal sphincter (LES) and is designed 
to augment a weak LES and minimize or eliminate GERD-related symptoms. 
2.2 
REGULATORY HISTORY 
The LINX System has been evaluated in two IDE studies under G060172.  A 
feasibility study enrolled 44 study subjects at 4 study centers (2 US, 2 OUS), with 
the first implant performed in February 2007.  The pivotal study enrolled 100 study 
subjects at 14 centers (13 US, 1 OUS), with the first implant in January 2009.  A 
Post Approval-Study of the LINX System is ongoing to supplement existing safety 
and efficacy data.  The LINX Reflux Management System received approval for 
U.S. marketing from the Food and Drug Administration (FDA) on March 22, 2012.  
The LINX device consists of a series of titanium beads each with a magnetic core 
connected together with independent titanium wires to form an annular shape, when 
implanted (Figure 1).  The attractive force of the magnetic beads is designed to 
provide additional strength to keep a weak LES closed.  During swallowing, the 
 
1DuPree et al JAMA Surg. 2014;149(4):328-334. doi:10.1001/jamasurg.2013.4323. 

 
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magnetic beads slide away from each other on the independent titanium wire 
“links” to allow esophageal distention as the bolus passes by (Figure 2).  
 
 
 
Figure 1 – Illustration of Implant, Closed 
Figure 2 – Illustration of Implant, Open 
 
The LINX System allows a surgeon, using existing laparoscopic techniques and 
instruments, to augment a weak sphincter and restore the barrier function of the 
LES.  The mechanism of action for the LINX device is to augment the sphincter’s 
capacity to resist gastric pressure by using magnetic forces.  For abnormal reflux to 
occur following implantation of the LINX device, gastric pressure must overcome 
both the native sphincter resistance and the magnetic bond between the LINX 
beads.  Prior to implant, the esophagus is sized to select a device that fits the 
external diameter of the esophagus.  At rest, the LINX device encircles the LES 
with each bead resting against an adjacent bead, which avoids compression of the 
esophagus and allows the patient to belch or vomit as necessary.  Upon swallowing, 
the magnetic bond between the beads is overcome by the higher pressures of 
peristaltic swallowing forces, and the device expands to accommodate a normal 
swallow (Figures 3-5).   
 
 
 
 
 
 
 
 

 
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Figure 3:  Preventing Reflux   Figure 4: During Swallow    Figure 5: Non-Compressive 
 
3.0 
STUDY PURPOSE AND OBJECTIVE 
The purpose of this study is to evaluate the safety and efficacy of LINX for its approved 
indication in patients who have had prior gastric surgery, specifically, LSG.  The objective 
of the study is to confirm safety and efficacy after LSG is similar to the outcomes that 
formed the basis for Premarket Approval (PMA) in order to support modification of the 
current labeling with a statement that prior gastric surgery with LSG has been evaluated 
for safety and efficacy. 
 
4.0 
STUDY RATIONALE 
The LSG procedure involves removal of the fundus.  As a result, fundoplication is 
extremely difficult to perform with the limited amount of fundus tissue present in patients 
with prior LSG.  Roux-en-Y Gastric bypass (RYGB) has been recommended as a 
conversion procedure for those who develop or continue to have reflux after LSG. 
However, LINX has been considered as an alternative and less invasive option that may 
potentially have fewer complications compared to RYGB.  Additionally, patients may not 
be interested in RYGB due its associated malabsorption.  The LINX device is implanted in 
the area of the gastroesophageal junction (GEJ), which is largely undisturbed with LSG.  
Patients with prior gastric surgery, such as LSG, have not to date been enrolled in clinical 
studies for the LINX device.  This study is the first to prospectively enroll and evaluate 
under protocol the LINX device for GERD in post-LSG patients. 
 
 
LINX device creates 
resistance with magnetic 
forces to prevent the LES 
Higher pressures from 
swallowing overcome 
the magnetic forces, 
LINX device does not 
compress the esophageal 
wall. 

 
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5.0 
STUDY DESIGN 
The study is an observational, multicenter, single-arm study with prospective enrollment.  
Based on the observational status of the study, No formal statistical hypothesis tests will 
be conducted.  Up to 30 patients meeting the eligibility requirements will be implanted 
with LINX and followed through 12-months after implant. Up to twelve (12) clinical sites 
will enroll subjects.  The study duration is expected to be about 36 months (24-month 
enrollment period and 12-month follow-up).  Safety evaluations will be ongoing 
throughout the duration of the study, starting at the implant procedure.  Efficacy endpoints 
will be evaluated at the 12-month visit.   
5.1 
ASSESSMENT OF SAFETY 
Safety will be assessed by evaluating device and/or procedure related adverse 
events, perioperative complications, device malfunctions, device removals, and 
hospital readmissions experienced by subjects post-LINX implant out to 12 
months.  Esophageal anatomy and functionality will be monitored by performing 
manometry and barium esophagram at 12-months post-implant.  This will allow for 
identification of any abnormal or atypical findings.  Further, device migration will 
be assessed by confirming device position at the GEJ by obtaining upright, bi-plane 
X-rays and device erosion will be assessed by performing endoscopy at the 12 
month visit. 
5.2 
ASSESSMENT OF EFFICACY 
Efficacy will be assessed by evaluating the percentage of subjects reporting at the 
12-month follow-up: 
• Normalization of total distal acid exposure time or at least 50% reduction in 
total distal acid exposure time compared to baseline 
• >50% reduction in total GERD-HRQL score compared to baseline (off  PPIs) 
• >50% reduction in average daily PPI dosage compared to baseline 
 
6.0 
SELECTION AND WITHDRAWAL OF SUBJECTS 
6.1 
INCLUSION CRITERIA 
Subjects included in the study must meet all the following criteria: 
1. Age >22 years 
2. Laparoscopic sleeve gastrectomy (LSG) for obesity >12 months prior to 
proposed device implantation date. 
3. Subject is a surgical candidate, i.e. is able to undergo general anesthesia and 
laparoscopic surgery. 
4. Documented typical symptoms of GERD for longer than 6 months 
(regurgitation or heartburn which is defined as a burning epigastric or 
substernal pain which responds to acid neutralization or suppression). 
5. Subject requires daily proton pump inhibitor or other anti-reflux drug therapy. 

 
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6. Total distal ambulatory esophageal pH must meet the following criteria:  pH 
<4 for >4.5% of the time.  Note:  Subjects shall have discontinued any GERD 
medications for at least 7 days prior to testing, with the exception of antacids 
up to the morning of testing.   
7. Subjects with symptomatic improvement on PPI therapy demonstrated by a 
GERD-HRQL score of <10 on PPI and >15 off PPI, or subjects with a >6 
point improvement when comparing their on PPI and off PPI GERD-HRQL 
scores. 
8. GERD symptoms, in absence of PPI therapy (minimum 7 days). 
9. If the subject is of child bearing potential must have a negative pregnancy test 
within one week prior to implant and must agree to use effective means of 
birth control during the course of the study. 
10. Subject is willing and able to cooperate with follow-up examinations 
11. Subject has been informed of the study procedures and the treatment and has 
signed an informed consent form. 
 
6.2 
EXCLUSION CRITERIA 
Subjects should be excluded from the study based on the following criteria: 
1. The procedure is an emergency procedure. 
2. Suspected or known allergies to titanium, stainless steel, nickel, or ferrous 
materials. 
3. Presence of ˃3 cm hiatal hernia as determined by endoscopy or barium 
esophagram. 
4. Subject had any major complications related to the laparoscopic sleeve 
gastrectomy that may interfere with, or increase the risks of the LINX procedure 
(such as, but not limited to, leaks from the gastric remnant and infection at the 
sleeve gastrectomy)  
5. Plans to surgically revise the gastric pouch (either known preoperatively or 
decided intraoperatively) 
6. Currently being treated with another investigational drug or investigational 
device. 
7. Suspected or confirmed esophageal or gastric cancer or prior gastric or 
esophageal surgery or endoscopic intervention for GERD (with the exception 
of sleeve gastrectomy). 
8. Distal amplitude <35 mmHg or <70% peristaltic sequences (if using 
Conventional Manometry) 
-or- 
If using High Resolution Manometry (exclude for any of the following): 
• Distal Contractile Integral (DCI) ≤ 450 mmHg·s·cm or 
• ≥ 50% ineffective swallows or  
• ≥ 50% fragmented swallows 

 
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(Fragmented swallows are defined as those with a ≥ 5cm break [large] in 
peristaltic integrity) 
9. Presence of esophagitis – Grade C or D (LA Classification). 
10. BMI >35. 
11. Symptoms of dysphagia more than once per week within the last 3 months. 
12. Diagnosed with Scleroderma. 
13. Diagnosed with an esophageal motility disorder such as but not limited to 
achalasia, nutcracker esophagus, or diffuse esophageal spasm or hypertensive 
LES. 
14. Subject has a history of or known esophageal stricture or gross esophageal 
anatomic abnormalities (Schatzki’s ring, obstructive lesions, etc.)  
15. Subject has esophageal or gastric varices 
16. History of/or known Barrett’s esophagus. 
Note:  The diagnosis of Barrett’s esophagus requires both endoscopic and 
histologic evidence of metaplastic columnar epithelium.  Endoscopically, 
there must be columnar epithelium within the esophagus. Histologically, the 
epithelium must be metaplastic, as defined by the presence of goblet cells.by  
17. Subject cannot understand trial requirements or is unable to comply with 
follow-up schedule 
18. Pregnant or nursing, or plans to become pregnant during the course of the study. 
19. Any reason which the Investigator believes may cause the subject to be non-
compliant with or unable to meet the protocol requirements. 
20. Subject has an electrical implant or metallic, abdominal implants. 
 
7.0 
STUDY SCHEDULE AND ASSSEMENTS 
Table 1 provides a schedule of data collection and follow-up windows.  It should be noted 
that certain data is collected while on and/or off GERD medications.   
Standard of care practices for antireflux surgery will be the basis of the assessments 
performed to determine if a subject is a candidate for the LINX device.  Investigators 
should refer to the LINX Instructions for Use (IFU) for prescribing information (see 
Appendix A).  Further, the study center will obtain appropriate study informed consent 
prior to evaluating the subject study specific evaluations.  Data will then be collected at the 
screening/baseline visit, the implant procedure and the hospitalization period following 
implant until discharge.  The subject will be followed at 2-weeks, 3-months, 6-months, and 
12-months post-implant, with data collection occurring at each time point.  Follow-up 
assessments may be completed by telephone or visit, with the exception of the X-rays, 
manometry, barium swallow, endoscopy and esophageal pH testing which must be 
conducted during a visit. 
Subjects will complete questionnaires to evaluate reflux-related symptoms (GERD-
HRQL and Foregut Symptom Questionnaire).  With the exception of the GERD-HRQL 

 
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at baseline, the questionnaires are completed off GERD medications for at least 7 days, 
with the exception of antacids which can be taken up until the morning of assessment.  At 
the screening/baseline visit, the questionnaires will be completed twice for the GERD-
HRQL – once on GERD medications and once off GERD medications for at least 7 days, 
with the exception of antacids which can be taken up until the morning of assessment 
(Table 2). 
 
Table 1:  Schedule of Data Collection and Follow-Up Windows 
X=All study subjects 
1Screening/baseline GERD-HRQL questionnaire is completed twice:  once on GERD medication and once off GERD 
medications for at least 7 days, with the exception of antacids which can be taken up until the morning of assessment.   
2 Completed/conducted off GERD medications for at least 7 days, with the exception of antacids which can be taken up 
until the morning of assessment. 
3Testing performed after implant and prior to discharge or within 7 days of implant, whichever occurs first. 
 
 
 
Screening/ Baseline 
Implant /Discharge 
2-week Post-Operative Visit (Day 7 – Day 21) 
3 months  (Day 76 – Day 104) 
6 months  (Day 150 – Day 210) 
12-month Visit  (Day 305 – Day 425) 
Data Collected 
 
X 
 
 
 
 
 
Demographics (gender, race) 
X 
 
 
 
 
X 
Height and Weight  
X 
 
 
 
 
X 
Medical History  
 
X 
 
 
 
 
Implant Procedure and Discharge Data 
X 
 
 
 
 
X 
Endoscopy (LA Grade Classification) 
X 
 
 
 
 
X 
Manometry/Motility 
X 
X3 
 
 
 
X 
Barium Esophagram  
 
X3 
 
 
 
X 
Upright, Bi-Planar X-Rays (AP and Lateral) 
X 
 
 
X 
X 
X 
GERD Medications 
X1 
 
 
X2 
X2 
X2 
GERD-HRQL  
X2 
 
 
X2 
X2 
X2 
Foregut Symptom Questionnaire 
X2 
 
 
 
 
X2 
Esophageal pH Measurements (off PPIs) 
 
X 
X 
X 
X 
X 
Device and/or Procedure Adverse Events  

 
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Table 2:  Completion of Questionnaires and GERD Medication 
Visit 
GERD-HRQL 
Foregut 
Baseline/Screening 
On GERD medications 
Off GERD medications 
Off GERD medications 
3-Month 
Off GERD medications 
Off GERD medications 
6-Month 
Off GERD medications 
Off GERD medications 
12-Month 
Off GERD medications 
Off GERD medications 
 
The data detailed in Table 3 will be obtained at each of the identified time points.  Use the 
following guidelines provide suggested methods and documentation for testing (Appendix 
B): 
• 4663 Guidelines for Endoscopy testing 
• 4664 Guidelines for X-rays testing 
• 4665 Guidelines for Barium Esophagram testing 
• 4666 Guidelines for Manometry/Motility testing 
 
Table 3:  Planned Assessments 
Visit 
Assessments/Data to be Collected 
Screening/ 
Baseline  
• 
Informed Consent 
• 
Demographics (Date of Birth, Gender, Race) 
• 
Height and weight  
• 
GERD History:  Duration of PPI use, Years with GERD, GERD New 
Onset or Pre-existing after LSG 
• 
GERD-HRQL (on/off PPIs) and Foregut Symptoms Questionnaire (off 
PPIs) 
• 
Baseline GERD related medication use 
• 
Esophageal pH measurements (off PPIs) 
• 
Endoscopy 
• 
Manometry/Motility 
• 
Barium Esophagram 
• 
Motivation for surgery 
• 
Inclusion/Exclusion criteria evaluation 
Implant/ 
Discharge 
 
• 
Surgery Date  
• 
Surgery start and stop time 
• 
Implanted device size 
• 
Concomitant procedures (e.g. hiatal hernia repair, cholecystectomy) 
• 
Barium esophagram and upright Bi-Planar X-Rays (AP and Lateral) 
• 
Discharge Date  
• 
Perioperative and device and/or procedure related adverse events 
2 Week  
• 
Device and/or procedure related adverse events 
3-Month  
• 
GERD-related medication use within the last 30 days 
• 
GERD-HRQL (off PPIs) and Foregut Symptoms Questionnaire (off PPIs) 
• 
Device and/or procedure related adverse events 
6-Month  
• 
GERD-related medication use within the last 30 days 
• 
GERD-HRQL (off PPIs) and Foregut Symptoms Questionnaire (off PPIs) 
• 
Device and/or procedure related adverse events 

 
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Visit 
Assessments/Data to be Collected 
12 Month 
Follow-up  
 
• 
Height and weight  
• 
GERD-HRQL (off PPIs) and Foregut Symptoms Questionnaire (off PPIs) 
• 
GERD-related medication use within the last 30 days 
• 
Esophageal pH testing (off PPIs) 
• 
Manometry/motility 
• 
Endoscopy  
• 
Barium esophagram and upright Bi-Planar X-Rays 
• 
Device and/or procedure related adverse events  
 
The data collection window for each visit is outlined in Table 4.  The 2-week follow-up 
visit is +/- 7 days from the anniversary of the implant procedure.  The 3-month follow-up 
visit is +/- 14 days from the anniversary of the implant procedure.  The 6-month follow-
up visit is +/- 30 days from the anniversary date of the implant procedure.  The 12-month 
follow-up visit is +/- 60 days from the anniversary date of the implant procedure.  
Table 4:  Follow-up Windows 
 
 
 
Visit 
Follow-up Window 
2-week (+7 days) 
7—21 days 
3 months (+14 days) 
76–104 days 
6 months (+30 days) 
150-210 days 
12 Months (+60 days) 
305-425 days 

 
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8.0 
SUBJECT FLOW CHART 
Standard of Care
Normal Surgical Work-up
Informed Consent Signed
Enrolled
Non-Standard of Care Work-up
(Study Specific Testing to Determine Eligibility)
Subject Meets All 
Inclusion/Exclusion Criteria
No
Screening Failure
Yes
Implant Procedure
LINX Device Implanted
No
Procedural Failure
Subject is follwed up for safety 
endpoint through 3 months
Subject Withdrawn From 
Study
Yes
Follow-up Subject in 
Accordance With Protocol
 
9.0 
RISK ANALYSIS 
9.1 
POTENTIAL RISKS 
The LINX Reflux Management System has been previously studied and known 
risks associated with the surgical procedure and device implant can be found in the 
Instructions for Use (Appendix A).  The proposed study will monitor the subjects 
through 12-months after implant for adverse events.  
 

 
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9.2 
POTENTIAL BENEFITS 
The potential benefits to subjects being implanted with the LINX device are the 
reduction or elimination of GERD-related symptoms and to reduce or eliminate 
dependence on GERD medications.  
10.0 
STATISTICAL PLAN 
No formal statistical hypotheses were pre-defined for this study.  Summary statistics are 
used to display results of effectiveness outcomes at each study time point.  For categorical 
parameters, this includes the number and frequency; and for continuous parameters, the 
mean, median, standard deviation, range and 95% confidence limits are presented.  For 
continuous efficacy parameters, the p-value for a one-sample, paired t-test to test if there 
is statistical evidence that the change from baseline is ≠ 0 is also given. 
10.1 
EFFICACY  
Efficacy will be measured by a comparison of GERD control before and after 
placement of the LINX Reflux Management System defined by esophageal pH 
measurements, GERD-HRQL score and PPI use. Subjects will serve as their own 
control. The change from baseline by follow-up will be calculated and summarized. 
10.1.1 ESOPHAGEAL ACID EXPOSURE 
Testing will be performed with subjects off PPIs. The subject’s total distal 
esophageal acid exposure time will serve as the control and will be 
compared to results at the 12-month visit.  Normalization for total distal 
ambulatory esophageal pH testing is defined as pH< 4 for < 4.5% of the 
time.  If longer pH evaluations are received the total distal acid exposure 
time will be recorded as a 24 hour average (e.g. 48 hour Bravo testing).  
Note:  The same testing equipment used at baseline should be used at 
subsequent follow-ups if possible. 
10.1.2 QUALITY OF LIFE 
Subjects GERD-HRQL (Health Related Quality of Life) scores will be 
assessed off all GERD medications. The subject’s baseline GERD-HRQL 
score will serve as the control and be compared to the subject’s GERD-
HRQL 12 months post implantation.  
10.1.3 USE OF PPIS 
Subject’s average daily dose of PPI will be evaluated. The subject’s baseline 
average daily dosage will serve as the control and be compared to the 
subject’s average daily dosage 12 months post-procedure. 
10.2 
SAFETY  
Safety will be assessed by the rate of (number and percentage of subjects 
experiencing) device and/or procedure related adverse events after LINX 

 
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placement out to 12 months.  Esophageal anatomy and functionality will be 
monitored by performing manometry and barium esophagram at 12-months post-
implant.  This will allow for identification of any abnormal or atypical findings.  
Further, device migration will be assessed by confirming device position at the 
GEJ by obtaining upright, bi-plane X-rays and device erosion will be assessed by 
performing endoscopy at the 12 month visit.  Incidence of device migration and 
erosion will be compared to current incidence rates (i.e. zero documented 
incidents of device migration and a low but established occurrence of esophageal 
erosions) to assess concurrence of the safety profile of study subjects to that of 
patients without a prior LSG. 
10.3 
ADDITIONAL ANALYSES 
• Summary statistics for components of the DeMeester score at 12 months 
• Percentage of subjects who discontinue daily PPI use at 3, 6 and 12 months. 
• Percentage of subjects who eliminate moderate or severe regurgitation as 
assessed by the Foregut Symptoms Questionnaire (FSQ) at 3, 6 and 12 months. 
• Percentage of subjects with extra-esophageal symptoms as assessed by the FSQ 
at 3, 6 and 12 months. 
• Percentage of subjects with esophagitis by endoscopy at 12 months. 
Side effects will be assessed by subject questionnaires including the following: 
• Percentage of subjects with ability to belch at 3, 6 and 12 months.  
• Percentage of subjects with ability to vomit at 3, 6 and 12 months. 
10.4 
SUBJECT POPULATION FOR ANALYSIS 
All subjects who meet the eligibility criteria, provide informed consent, complete 
baseline assessments and undergo the LINX procedure will represent the study 
population for analysis.  Data analyses will be performed on available data at the 
follow-up visits.  
 
11.0 
STUDY PROCEDURES AND MANAGEMENT 
11.1 
CLINICAL STUDY REGISTRATION 
The study will be registered by the Sponsor at www.clinicaltrials.gov. 
11.2 
STUDY CENTER SELECTION AND PARTICIPATION 
Study centers interested in participating in this study will be assessed for their 
ability to fully and appropriately participate in the study.  In general, study centers 
will be selected if patient volume is adequate to support enrollment of patients 
into the study and the participating physician(s) are qualified by education, 
training and surgical experience.   
No site will enroll more than 6 subjects without prior written approval provided 
by the Sponsor. 

 
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11.3 
INFORMED CONSENT 
Prior to IRB submission, the Investigator or designee will prepare an Informed 
Consent Form (ICF) in accordance with this study protocol and all regulatory 
requirements (e.g. where applicable, 21 CFR Part 50 and in accordance with the 
Declaration of Helsinki) using the sample ICF provided (Appendix C).  A copy 
of the final IRB approved ICF must be submitted to Torax Medical and a site 
must be activated by Torax Medical prior to enrolling patients at that 
investigational center.  All study patients (or their legal guardian) must document 
their consent by signing an IRB-approved ICF prior to completing any protocol-
specific assessments that are not considered standard of care.   
11.4 
INSTITUTIONAL REVIEW BOARD 
This protocol, informed consent form (ICF), and authorization for the use and 
disclosure of health information (as applicable) must be reviewed and approved 
by the study center’s IRB before any study patient is enrolled.  Changes to the 
protocol must be approved in writing by Torax Medical and the IRB (as 
applicable) before the change is implemented. 
Prior to study patient enrollment, a signed copy of the IRB approval letter 
addressed to the Investigator and the final approved ICF must be submitted to 
Torax Medical.  The letter should reference this protocol by title, date or 
number/revision number as well as the approved ICF and HIPAA Authorization 
(as applicable).  Investigators are responsible for submitting and obtaining initial 
approval and continuing approval from the IRB and forwarding copies of the 
approval letters to Torax Medical.  The original letters are to be kept in the study 
center’s regulatory file designated for this study. 
The Investigator will notify the Sponsor within five (5) working days of withdrawal 
of IRB approval. 
11.5 
SITE ACTIVATION 
A study center may not begin enrolling subjects until the Sponsor provides 
notification that the site has provided all required study start-up documents and 
completed training.  At minimum, the Principal Investigator at the study center 
will be notified in writing of “Site Activation” when start-up activities have been 
completed.  Upon receipt of this notification, the study center may begin enrolling 
subjects.   
11.6 
STANDARD OF CARE 
As part of screening/baseline, all patients will undergo the standard of care anti-
reflux surgery work-up.  The anti-reflux surgery work-up used for the study 
enrollment should be completed within the 1-year time period prior to signing of 
the study ICF.  For purposes of the study, the questionnaires (GERD-HRQL, 

 
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Foregut Symptom Questionnaire, and RDQ) will be considered standard of care to 
facilitate pre-screening of patients.  However, only questionnaires completed by a 
subject who has provided informed consent for the study will be accessible to the 
Sponsor.   
11.7 
SCREENING/ENROLLMENT  
Potential study subjects will be identified from the Investigator’s practice or by 
referral.  During the screening/enrollment visit, informed consent will be obtained 
prior to any study specific assessments and eligibility against the inclusion and 
exclusion will be confirmed prior to implant.   
11.8 
DEVICE TRACKING 
Devices used for the study will be tracked (by lot number and number of beads) 
and captured on the case report forms. 
11.9 
ADVERSE EVENT REPORTING 
If an intraoperative decision is made to not implant the LINX device, the subject 
will be monitored for procedure related adverse events for a period of at least 
three months (90 days) or longer if needed until resolution before withdrawing the 
subject from the study. 
If a decision is made to explant the LINX device during the study, the subject will 
be monitored for explant-related adverse events for a period of at least three 
months (90 days) or longer if needed until resolution before withdrawing the 
subject from the study.  No other study testing and/or questionnaires would be 
required after the device is explanted. 
For all other subjects starting at the time of implantation and proceeding throughout 
the duration of the follow-up period, the Investigator will closely monitor each 
subject for the development of device and/or procedure related adverse events.  A 
subject presenting with new onset dysphagia, abdominal pain, nausea, or vomiting, 
may be assessed for device migration and/or erosion if symptoms persist and benign 
causes cannot be established, at the discretion of the Investigator.  This may include 
additional, non-study visit, x-rays or endoscopic evaluation.  Adverse events will 
continue to be monitored at each of the study follow ups until resolution and/or 
study completion. 
For the purposes of this study, a reportable event will be defined as any untoward 
medical occurrence which has a strong relationship to the LINX device and/or 
implant procedure and another etiology is unlikely.  The Investigator must decide 
whether each event meets the definition of a Serious Adverse Event (SAE). All 
device and/or procedure related serious adverse events (SAE) must be reported 
immediately (within 5 days of discovery) to Torax Medical.  SAE reporting to the 
IRB is per institutional policy. 
 
 

 
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An AE is considered serious if it meets one or more of the following criteria: 
• Is life-threatening or results in death 
Note:  The term “life-threatening” in the definition of “serious” refers to an 
event in which the subject was at risk of death at the time of the event; it does 
not refer to an event that hypothetically might have caused death if it were more 
severe. 
• Requires subject hospitalization > 24 hours 
• Requires prolongation of an existing hospitalization 
• Results in persistent or significant disability/incapacity 
• Results in fetal distress, fetal death, or a congenital anomaly or birth defect 
• Requires intervention to prevent permanent impairment or damage of 
body function or structure 
• Other serious important medical events that do not fit in the other 
outcomes and may jeopardize the patient and may require medical or 
surgical intervention to prevent one of the other outcomes 
 
Unanticipated Adverse Device Effects 
Unanticipated adverse device effects (UADEs) include any serious adverse effects 
on the health or safety of a study subject or any life-threatening problem or death 
caused by, or associated with, the LINX device that are not typically associated 
with the procedure or the device.  All unanticipated adverse device effects must 
be reported to the IRB within 10 working days and to Torax Medical within 24 
hours after the Investigator first learns of the adverse device effect.   
 
The following definitions for rating the severity of adverse events will be used: 
 
Mild 
Awareness of signs of symptoms, but easily 
tolerated; are of minor irritant type; causing no 
loss of time from normal activities. 
Moderate 
Discomfort intense enough to cause interference 
with usual activities. 
Severe 
Incapacitating with inability to do work or usual 
activities. 
 
11.10 SUBJECT COMPLETION AND WITHDRAWAL 
All study subjects have the right to withdraw their consent to participate at any time 
during the study.  Whenever possible, the site staff should obtain written documentation 
from the subject of his/her request to withdraw consent.  If the site staff is unable to 
obtain written documentation, all information regarding the subject’s withdrawal must be 
recorded in the subject’s medical record.   

 
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On completion of the study (either by completion of protocol requirements or 
withdrawal), the Withdrawal/Completion CRF will be completed.  
A subject may withdraw (or be withdrawn) from the study prematurely for the following 
reasons:  
• Withdrawal of consent by subject 
• Adverse event (Adverse Event Log or SAE CRF must be completed) 
• Protocol deviation 
• Lost to follow-up (In case of early withdrawal of a subject, at least three 
(3) documented attempts should be made to contact the subject and have 
them come into the clinic). 
• Termination of study by the Sponsor 
• Investigator believes it is in the best interest of the subject 
• Other (must be specified) 
12.0 
ROLE AND RESPONSIBILITIES 
Each investigational center will identify appropriate personnel to perform all study tasks.  
12.1 
INVESTIGATOR 
• This clinician will have responsibility to treat all subjects. 
• Documents all reportable adverse events that occur during the study. 
• Be responsible for signing the CRFs. 
• Be responsible for providing medical care to subjects during the study. 
• Have responsibility for determining eligibility. 
• Conduct baseline assessments of the subject’s GERD. 
• Interview subjects about their GERD symptoms. 
• Be available for each subject follow-up visit.   
12.2 
STUDY COORDINATOR 
In addition to the Investigator, a Study Coordinator will be identified at each 
investigational center to facilitate and manage the study.   
 
13.0 
STUDY CENTER DOCUMENTATION 
A study center site will provide the following documentation to Torax Medical prior to a 
site being activated to enroll patients: 
• Study training/initiation completed for the Investigators and study staff listed 
on the delegation log  
• Signed clinical trial agreement (CTA) 
• Current signed curriculum vitae and medical licenses for all Investigators 
listed on the CTA 

 
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• Financial disclosure for all Investigators listed on the CTA 
• IRB approval letter and approved ICF 
 
14.0 
STUDY PATIENT RECRUITMENT AND RETENTION PLAN 
As needed, the Sponsor will provide study centers with materials and financial support to 
recruit patients for the study.  All recruitment activities will require prior approval by the 
IRB before implementation.   
Efforts will be made to ensure the retention and compliance of study patients once 
enrolled.  Examples of strategies for subject retention include: 
• Instruct study centers to obtain multiple contact numbers and addresses from a 
subject to make it easier to reach the participant. 
• Counsel patients about the importance of returning to follow-up during informed 
consent and follow-up visits. 
• Accommodate a subject’s schedule as much as possible to make the follow-up as 
convenient as possible. 
• Encourage the study centers to continue open communication with enrolled 
subjects and to schedule follow-up visits early in the protocol-defined window.   
• Provide database-generated follow-up schedules to study centers and discuss 
dates of upcoming visits. 
• Monitor follow-up rates closely so that follow-up problems can be identified and 
addressed as soon as possible. 
• Request that study centers thoroughly document all attempts to contact enrolled 
subjects. 
15.0 
DATA HANDLING AND RECORD KEEPING 
15.1 
CONFIDENTIALITY 
Information about study subjects will be kept confidential and managed according to 
applicable laws, regulations and guidelines.  All subject information documented on 
CRFs will be referenced by a subject’s identification (ID) number and initials only.  If 
supplemental laboratory or imaging reports are submitted into the study, the subject’s 
name or other prohibited identifiers must be deleted and the subject initials and ID 
number added to each item.  A subject’s privacy and personal health information will be 
protected as required by law. 
 
 

 
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15.2 
SOURCE DOCUMENTS 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  
Source data are contained in source documents.  Examples of these original documents, 
and data records include: hospital records, clinical and office charts, laboratory notes, 
surgical notes, memoranda, subjects’ diaries, questionnaires or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate and complete, microfiches, 
photographic negatives, microfilm or magnetic media, X-rays, subject files, and records 
kept at the pharmacy and at the laboratories involved in the clinical trial. 
 
15.3 
CASE REPORT FORMS 
The study case report form (CRF) is the primary data collection instrument for the study 
(Appendix D).  All data requested on the CRF must be recorded.  All missing data must 
be explained.  If a space on the CRF is left blank because the procedure was not done or 
the question was not asked, write “N/D”.  If the item is not applicable to the individual 
case, write “N/A”.  All entries should be printed legibly in ink.  If any entry error has 
been made, to correct such an error, draw a single straight line through the incorrect entry 
and enter the correct data above it.  All such changes must be initialed and dated.  DO 
NOT ERASE OR WHITE-OUT ERRORS.  For clarification of illegible or uncertain 
entries, print the clarification above the item, then initial and date it. 
 
15.4 
RECORDS RETENTION 
The Investigator/institution will retain the study-related essential documents until two 
years after the final data analysis is complete. 
 
16.0 
QUALITY ASSURANCE AND QUALITY CONTROL 
The Principal Investigator at each study site is responsible for assuring that accurate and 
complete data are collected and sent to the Sponsor.  Data will be reviewed periodically 
by the Sponsor for missing data points, incomplete information, and discrepancies.  
When necessary, issues will be resolved by electronic mail, telephone, facsimile, or site 
visit.  The Investigator will permit study-related monitoring, audits, and inspections by 
the IRB, the Sponsor, government regulatory bodies, and institutional compliance and 
quality assurance groups of all study related documents (e.g. source documents, 
regulatory documents, data collection instruments, study data etc.).  The Investigator will 
ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, 
diagnostic laboratory, etc.).   

 
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17.0 
PUBLICATION PLAN 
Neither the complete nor any part of the results of the study carried out under this 
protocol, nor any of the information provided by the Sponsor for the purposes of 
performing the study, will be published or passed on to any third party without the 
written consent of Torax Medical.  Any Investigator involved with this study is obligated 
to provide the Sponsor with complete test results and all data derived from the study.