Radiofrequency Energy Delivery to the Lower Esophageal Sphincter (Stretta) in Sleeve Gastrectomy Patients With GERD
Phase: NA
Conditions: GERD, Morbid Obesity
Sponsor: Montefiore Medical Center

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Title: 
Radiofrequency Energy Delivery to theLower Esophageal Sphincter 
(Stretta Procedure) in Sleeve Gastrectomy Patients with GERD 
 
 
 
Protocol No: 
IRB# 2015-5661 
Protocol Date: 
Revision No.:                   
6/22/16 
3.1 
 
 
Erin Moran-Atkin, MD 
Montefiore Medical Center 
Department of Bariatric and Minimally Invasive Surgery 
111 East 210th St 
Bronx, NY, 10467 
Phone (718) 920-4800  
email: EMorana@Montefiore.org 
 
 
 
IRB NUMBER: 2015-5661
IRB APPROVAL DATE: 06/28/2016

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TABLE OF CONTENTS……………………………………………………………………………..2 
ABBREVIATIONS AND DEFINITIONS OF TERMS……………………………………………...4 
OVERVIEW…………………………………………………………………………………………..5 
1 
BACKGROUND INFORMATION AND RATIONALE………………………………………………….5 
1.1 INTRODUCTION……………………………………………………………………………………..5 
1.2 COMPLIANCE STATEMENT………………………………………………………………………..5 
1.3 RELEVANT LITERATURE AND DATA…………………………………………………………….6 
2 
STUDY OBJECTIVES……………………………………………………………………………………..6 
2.1 PRIMARY OBJECTIVE ………………………………………………………………………………6 
2.2 SECONDARY OBJECTIVES ………………………………………………………………………...7 
3 
INVESTIGATIONAL PLAN……………………………………………………………………………….7 
3.1 GENERAL SCHEMA OF STUDY DESIGN…………………………………………………………..7 
3.2 CRITERIA FOR EVALUATION……………………………………………………………………....8 
 
3.2.1 
PRIMARY ENDPOINT ……………………………………………………………………...8 
 
3.2.2 
PRIMARY ENDPOINT ……………………………………………………………………...8 
 
3.2.3 
INCLUSION CRITERIA …………………………………………………………………….8 
 
3.2.4 
EXCLUSION CRITERIA ……………………………………………………………………8 
4 
STUDY PROCEDURES.................................................................................................................................9 
4.1 CLINICAL ASSESMENTS.....................................................................................................................9 
4.2 CLINICAL LABORATORY MEASURMENTS..................................................................................10 
4.3 PRE-PROCEDURE TESTING……………………………………………………………………......10 
5 
STUDY ADMINISTRATION …………………………………………………………………………….11 
5.1 DATA COLLECTION AND MANAGEMENT……………………………………………………...12 
5.2 CONFIDENTIALITY…………………………………………………………………………………12 
5.3 REGULATORY AND ETHICAL CONSIDERATIONS……………………………………………..13 
5.3.1 
RISK ASSESSMENT………………………………………………...…………………………..13 
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5.3.2 
POTENTIAL BENEFITS OF STUDY PARTICIPATION ...........................................................13 
5.3.3 
RISK-BENEFIT ASSESSMENT  ..................................................................................................13 
5.4 INFORMED CONSENT……………………………………………………………………………...14 
5.5 PAYMENT TO SUBJECTS/FAMILY………………………………………………………………14 
6 
STATISTICAL CONSIDERATIONS…………………………………………………………………….14 
6.1 STATISTICAL METHODS...............................................................................................................14 
6.2 SAMPLE SIZE AND POWER...........................................................................................................14 
6.3 PATIENT ACCRURAL...................................................................................................................14 
6.4 INTERIM ANALYSIS AND STOPPING RULES...........................................................................14 
7 
PUBLICATION............................................................................................................................................15 
8 
REFERENCES.............................................................................................................................................16 
 
 
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ABBREVIATIONS AND DEFINITIONS OF TERMS 
 
 
 
 
 
 
 
 
 
GERD 
RYGB 
SG 
HRQL 
 
Gastroesophageal Reflux Disease 
Roux-en-Y Gastric Bypass 
Sleeve Gastrectomy 
Health Related Quality of Life 
EMR 
 
Electronic Medical Record 
FDA 
 
Federal drug administration 
RSI 
 
Reflux Symptom Index 
LES 
 
Lower esophageal sphincter  
PPI 
 
Proton pump inhibitor 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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OVERVIEW 
1. Background Information and Rationale 
 
1.1 Introduction 
 
Gastroesophageal reflux disease(GERD) is a widely prevalent medical disorder in the United 
States with a spectrum of treatment options ranging from dietary modification, to various 
pharmacologic treatments, to an array of available surgical and endoscopic procedures. There is a 
well-described correlation between obesity and symptoms of GERD. The morbidly obese patients 
undergoing evaluation for bariatric surgery are to characterize any GERD-like symptoms as this will 
assist in directing surgical therapy. Generally, it is recommended that patients with severe GERD 
undergo Roux-en-Y gastric bypass(RYGB) rather than a sleeve gastrectomy (SG) as RYGB has 
proven to be the most effective surgical treatment for GERD in the morbidly obese patient. The 
number of bariatric procedures performed in the United States has increased significantly in the 
recent years.  Out of all bariatric procedures SG is the most commonly performed in the United 
States, as it has proven to be a very safe procedure with excellent weight loss. However, the incidence 
of de novo GERD and the effect of SG on patients with preexisting GERD remain 
controversial.Although some authors report high incidence of de novo GERD and worsening of 
previous reflux symptoms, there is also data showing improvement of symptoms post SG. 
Management of GERD after SG poses an interesting challenge, as traditional invasive procedures 
likeNissen fundoplication are not available due to an altered gastric anatomy. The alternative is to 
perform a conversion to RYGB, which represents increased morbidity to patient and significant cost. 
 
A large number of endoscopic procedures have been introduced in the past for the management of 
GERD as an alternative to the surgical anti-reflux procedures with various degrees of success. One of 
the few non-invasive methods for managing GERD that is still available on the market and widely 
used is Stretta.  Stretta delivers Radio Frequency energy (RFe) to the LES resulting in increased LES 
pressure.  In 2000, the FDA approved the Stretta system as treatment for patients diagnosed with 
GERD. Stretta allowsan alternative for treatment in patients who are not willing or able to undergo 
surgery. The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) published 
clinical practice guidelines that endorsed Stretta as an appropriate therapy for treatment of GERD in 
patients >18, with at least 6 months of symptoms partially or completely responsive to 
pharmacotherapy and who are unable or unwilling to undergo laparoscopic Nissen fundoplication. 
There are to date no studies evaluating the use of Stretta in management of patients with GERD 
symptoms after sleeve gastrectomy. 
1.2 Compliance Statement 
 
This study will be conducted in full accordance of all applicable Montefiore Medical Center 
Research Policies and Procedures and all applicable Federal and state laws and regulations including 
45 CFR 46, and the HIPAA Privacy Rule. Any episode of noncompliance will be documented. 
 
The investigators will perform the study in accordance with this protocol, will obtain 
consentand assent when applicable (unless a waiver is granted), and will report unexpected problems 
in accordance with The Montefiore Medical Center IRB Policies and Procedures and all federal 
requirements. Collection, recording, and reporting of data will be accurate and will ensure the 
privacy, health, and welfare of research subjects during and after the study.  
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1.3 Relevant literature and Data 
 
 
Bariatric surgery is an effective long term treatment for morbid obesity. The number of 
bariatric procedures performed in the United States has increased significantly in the recent years. 
The American Society for Metabolic and Bariatric Surgery (ASMBS) estimates that in The United 
Statesin 2013 approximately 179 thousand bariatric caseswere performed. The number of sleeve 
gastrectomiespreformed in the US has increased from being only 17% of the bariatric cases in 2011 to 
over 42% in 2013 and continues to increase. This increase in numbers is because SG has proven to be 
a very safe procedure with excellent weight loss results. There is conflicting data on theeffect of SG 
on patients with preexisting GERD. Although the pathophysiology is not fully understood, GERD 
following SG is usually attributed to a decreased lower esophageal sphincter (LES) pressure, 
disruption of the sling fibers, dissection of the angle of His or elevated intragastric pressure. In cases 
with severe GERD, patients may have to undergo a revision to RYGB, as this is the only available 
treatment for refractory GERD after SG. 
 
 
Studies investigating the incidence of GERD following SG have many limitations and are 
poorly designed. First, the surgical technique is not standardized. Different techniques can result in 
various sleeve sizes and can also result in gastric stenosis at the incisura or in a residual large fundus, 
which can all, affect the incidence of GERD postoperatively. Second, the true incidence of GERD in 
patients undergoing SG is largely unknown because patients do not routinely undergo preoperatively 
workup for GERD. Third, many patients develop non-specific gastrointestinal symptoms like 
regurgitation, bloating and chest pain, which are sometimes attributed to GERD or even hiatal hernia 
without any confirmationof the diagnosis.The postoperative use of proton pump inhibitors or other 
antisecretory medications as well as initial healing time followed by relaxation/dilatation of the 
gastric sleeve a few months following SG can influence symptoms of GERD. Therefore, data 
regarding the incidence of GERD following SG should be obtained at least 6 months postoperative at 
which time the majority of weight loss has been achieved, medications stopped and changes have 
stabilized. 
 
 
There has been in recent years a large number of endoscopic procedures that have been used as 
an alternative to the surgical anti-reflux procedures with various degrees of success.The delivery of 
RFe to the LES by the Stretta device results in increased LES pressure. The Stretta device is FDA 
approved and has excellent results in the treatment of GERD symptoms in the standard population.  
The aim of this study is to objectively investigate the effect of RFe to the LES in patients who 
develop GERD related symptoms after SG. Patients who experience GERD related symptoms 6 
months after SG will undergo the Stretta procedure. The data collected from EGD, pHmonitoring in 
junction with GERD Health-Related Quality of Life (HRQL) questionnaire prior to the Stretta 
procedure, will be compared with data following the Stretta procedure at 6, 12 and 24 months.  
 
2. Study Objectives 
 
2.1 Primary Objective 
The primary objective of this prospective study is to evaluate the treatment success as measured by 
percent reduction of symptoms.  Following the use of radiofrequency energy delivered to the lower 
esophageal sphincter as a treatment of symptomatic GERD, in patients who have undergone sleeve 
gastrectomy for morbid obesity. The endpoint of interest is whether patients achieved a 50% 
reduction in symptoms as measured by RSI and HQRL indices. 
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2.2 Secondary Objectives 
The secondary objectives are: 
 
To determine the pH findings in patients with symptomatic GERD after SG   
 
To determine the effects of gastric emptying and its association to GERD in patients after SG 
 
To follow the long term effect of Stretta in patients with symptomatic GERD after SG 
 
3. Investigational Plan 
 
3.1 General Schema of Study Design 
 
3.1.1 
Multicenter prospective study 
This is a multicenter prospective study involving ten to fifteen tertiary medical centers. We expect to 
enroll at least twenty patients per center. Pre-procedure all enrolled patients will undergo a battery of 
testing in order to ensure that they are an adequate candidate for Stretta.  The workup will include:  
- pH monitoring(off medication) 
- EGD with biopsies 
- Barium swallow  
- Gastric Emptying study 
- RSI and GERD-HQRL 
- Manometry, if dysphagia is reported 
 
This will be followed by endoscopic radiofrequency energy delivery utilizing the Stretta system. 
Patients will be followed and evaluated at 6, 12, and 24 months with RSI and GERD-HRQL scoring 
as well as interval pH testing. At 6 and 12 months those subjects with initial abnormal pH,Gastric 
emptying or EGD will repeat pH monitoring,gastric emptying and EGD 
 
3.1.2 
Number of sites 
10 to 15 tertiary medical centers. The proposed sites that have expressed interest are: 
 
 
- Montefiore Medical center, Bronx, NY 
- Ohio State University, Columbus, OH 
- Duke University, Durham NC  
- Emory University, Atlanta, GA 
- Oregon Health & Science University, Portland, OR 
- Loyola University, Chicago, IL 
- New York University(NYU), NY, NY 
- Oregon Clinic, Portland, OR 
- The Methodist Hospital, Houston, TX 
- Buffalo General Hospital, Buffalo, NY  
- Our Lady of the Lake Hospital, Baton Rouge, LA 
- Brigham and Women’s Hospital, Boston, MA 
- University of California Irvine Medical Center, Orange County, CA 
- Memorial Hermann Hospital, Houston, TX 
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- Cleveland Clinic, Cleveland, OH 
- Columbia University Medical Center, NY, NY 
- UH Case Medical Center, Cleveland, OH 
- Rush University Medical Center, Chicago, IL 
 
3.1.3 
Enrollment 
 
Patients may be enrolled prospectively or retrospectively up to 6 months following Stretta procedure. 
 
3.2 Criteria For Evaluation 
3.2.1 Primary Endpoint 
 
Primary endpoint will be based RSI and HQRL indices and will be a determination of 
whether the patient achieved at least a 50% reduction in symptoms at the 6 12 and 24 month 
points as compared to baseline. 
 
3.2.2 
Secondary Endpoints 
 
 
Improvement in esophageal pH exposure. 
 
Cessation or decreased in use of anti-reflux medication 
 
Determination of gastric dysmotility as a contributory factor in GERD after SG 
 
Objective improvement or resolution of esophagitis utilizing LA classification.  
 
3.2.3 
Inclusion Criteria 
Participants will be men and women between the ages of 18 and 80 who have undergone 
sleeve gastrectomyat least 6 months prior to enrollment as treatment of morbid obesity and 
who have one or more of the following: 
1. Symptomatic reflux: (heartburn, chest discomfort, asthma/chronic cough, laryngitis, 
nocturnal aspiration or regurgitation) 
2. On a PPI with GERD-related symptoms  
3. On a PPI but like to discontinue them 
 
3.2.4 
Exclusion Criteria 
 
1. Age <18 or > 80 
2. History of a severe psychiatric disorder: including suicidal ideation, or admission to a 
psychiatric institution. 
3. Unable or unwilling to consent for an invasive procedure. 
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4. History of intestinal leak after surgery.  
5. History of revisional bariatric surgery 
6. Significant sleeve abnormalities such and twist or large fundus  
7. Hiatal hernia(>2cm) 
8. Pregnancy 
9. Inability to comply with study protocols and procedures 
10. Esophageal stricture, Eosinophilic Esophagitis or Achalasia 
11. Prior esophageal surgery or therapy for Barrett’s Esophagus 
12. Grades 3 or 4 esophagitis 
13. Gastric or esophageal varices 
14. History of obstruction of the small bowel or inflammatory bowel disease 
15. Pacemaker or implanted cardiac defibrillator 
16. Coagulopathy or use of anticoagulants 
17. ASA classification >3 
18. Scleroderma or other connective diseases 
19. Use of imunosuppressive medications.  
 
 
4. Study Procedures 
A Schedule of Events representing the required testing procedures to be performed for the duration of 
the study is diagrammed in Appendix 1. 
A description of the assessment and work-up to be performed on the initial evaluation, pre-procedure 
testing, and each of the post-procedural follow-ups is provided in Appendix 2. 
Prior to conducting any study-related activities, written informed consent and the Health Insurance 
Portability and Accountability Act (HIPAA) authorization must be signed and dated by the subject. 
4.1 Clinical Assessments 
 
Demographics 
Demographic information (date of birth, gender, race) will be recorded at screening. 
 
Medical/Surgical History 
Relevant medical history, including history of current disease, information regarding underlying 
diseases and prior surgical history will be recorded at screening. 
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Physical Examination 
A complete physical examination will be performed by either the investigator or a subinvestigator 
who is a physician at the participating center.  Qualified staff (MD, NP, RN, and PA) may 
complete the abbreviated physical exam at all other visits.  New abnormal physical exam findings 
must be documented and will be followed by a physician or other qualified staff at the next 
scheduled visit. 
 
Vital Signs 
Standard vital sign measurements will be captured at screening, during pre-procedure workup, 
peri-procedure and at each subsequent follow-up visit. 
 
Imaging/Endoscopy 
The investigator or subinvestigator to assure appropriate inclusion and exclusion criteria are met 
will review all relevant prior imaging and endoscopic evaluations. 
 
Concomitant Medications 
All concomitant medication and concurrent therapies will be documented at initial screening and 
during pre-procedure evaluation. All changes in medications and doses will be captured at each 
follow-up visit.  Dose, route, unit frequency of administration will be documented. 
4.2  Clinical Laboratory Measurements  
Pregnancy Test 
A urine or serum pregnancy test will be obtained from female subjects who are of childbearing 
age prior to Stretta procedure. Subsequent pregnancy tests may be performed at follow-up visits, 
at the discretion of the investigator. 
4.3 
Pre-procedure Testing 
 
EGD 
The upper endoscopy of SG patients with GERD symptoms will be performed under IV sedation 
per institutional guidelines.  Biopsies of any suspicious lesions and of any evidence of esophagitis 
will be taken. Evidence of esophagitis will be scored by histology and according to LA 
classification:  
Grade A 
One or more mucosal breaks < 5 mm in maximal length 
Grade B 
One or more mucosal breaks > 5mm, but without continuity across mucosal 
folds 
Grade C 
Mucosal breaks continuous between > 2 mucosal folds, but involving less than 
75% of the esophageal circumference 
Grade D 
Mucosal breaks involving more than 75% of esophageal circumference 
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Following upper endoscopy, assuming that there are no contraindications noted, the patient will 
then undergo a motility and 24 hour pH testing. 
 
pH monitoring 
Bravo pH monitoring will be performed off proton-pump inhibitors (PPI) or anti-secretory drugs. 
Subjects taking any of these medications will be required to discontinue them for at least one 
week. Subjects who are unable to discontinue their medications will be excluded from the study.  
At the discretions of each site and pending site availability catheter based pH monitoring can be 
used. 
 
Barium Swallow 
The Barium swallow will be performed per institutional guidelines. Assessment of esophageal 
motility and any evidence of dilation will be recorded. Subjects who have any evidence of 
abnormally enlarged sleeve, evidence of twist, or large residual fundus will be excluded from 
study. 
Gastric Emptying Study  
The Gastric Emptying study will be performed per institutional guidelines. Assessment of gastric 
emptying for all patients at 1, 2, 3 and 4 hours, will be documented. Subjects who have severe 
gastroparesis(over 50% retention at 4 hours) will be excluded from study. 
 
RSI/HQRL 
Patients will complete a GERD Health Related Quality of Life questionnaire (HRQL) 
(Addendum 1) and Reflux Symptom Index (RSI) (Addendum 2) at baseline off medications and 
following the Stretta procedure at 6,12 and 24 months if patient has required to restart 
antisecretory medication at any time a new trial to discontinue medication will be attempted and 
questionnaires shall be completed while off medications for at least 1 week. 
 
Manometry 
Esophageal manometry will be performed in any patients who refer any symptoms that may 
suggest dysphagia or if contrast study shows evidence of severe dismotility, if positive for 
motility problems it will exclude subject from study. 
5. Study administration 
Catheter-based manometry and Bravo pH monitoringStudies 
The use of manometry will be at the discretion of the physician if there is any suspicion of motility 
abnormalities. All subjects will have pH monitoringas baseline prior to Stretta procedure if abnormal 
it will be repeated at 6 month and 12months. Results will be collected and reviewed by the 
investigators at each site and reported using confidential password protected files.  
As part of the submission and review process the studies will be inspected by the designated 
investigator and evaluated for: 
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1. Quality of data collected. 
2. Correct use of the diary information and patient symptoms entries. 
3. Artifacts will be noted and excluded from the calculation. 
4. Confirmation of diagnosis regarding the presence or absence of reflux events, and correlation of 
reflux events with patient symptoms. 
5. Data will be collected of the following data entries: 
a. LES length 
b. LES pressure 
c. % normal peristalsis 
d. Total number of reflux events 
e. Time pH < 4 min 
f. Total fraction time % pH < 4 
g. DeMeester Score 
h. Correlation of symptoms with reflux events 
Stretta Procedure 
Stretta will be performed while patient is on anti-secretory agents. Subjects will continue taking these 
medications for four weeks post procedure.  After the fourth week they will decrease to half dose for 
2 week and then discontinue medication. 
Stretta is a safe, non-invasive FDA approved procedure performed endoscopically under moderate 
sedation or general anesthesia which uses radio frequency (RF) energy applied to the lower 
esophagus over 14 minutes per a specific FDA approved protocol and as per package instructions for 
the device. Under endoscopic guidance, a soft tip guide wire will be advanced thru the gastric sleeve 
and into the duodenum. After removal of the endoscope, the Stretta catheter will be advanced over the 
wire and the Stretta balloon initially positioned 1 cm above the previously located GE junction. 
Following the established manufacturer required protocol, the balloon is inflated and needles 
deployed for each successive treatment level, with RF energy applied under the control of the Stretta 
version 2 generator. 
5.1 Data Collection and Management 
Data will be obtained through subject interview and survey, and medical records. Privacy and security 
will be maintained by minimizing the amount of identifiable data as much as possible.  All 
identifiable patient information will be kept at each site in a password protected file and deleted at the 
conclusion of the study. All de-identified information will be compiled in confidential password 
protected Access spreadsheets on cloud bases storage that are password protected.   
All necessary identifiers will be used only to identify the relevant source documents (as described 
above).  Following this, surrogate numbers will be given to identify the patients for data analysis.  All 
identifiers will be deleted from the file.  This information will remain at each institution in a separate 
password protected file that served as the initial list of cohort patients to be searched until after 
completion of the study period and analysis, at which point it will be deleted.  
As part of the usual standard of patient care for bariatric surgery and reflux corrective procedures, the 
principal investigator and study coordinator designees have the responsibility to monitor timely 
collection and regularly examine the results to make sure the study protocol is implemented correctly 
with no unforeseen side effects. The principal investigator and co-investigators will review data 
collected every three months, to monitor trends within the different outcome measures, as well as 
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evaluate side effects and other unforeseen events. The principal investigator will report to the IRB 
any unexpected and adverse events or other unanticipated problems involving risks to subjects or 
others within 30 calendar days and within 7 days for serious adverse events. 
5.2 Confidentiality 
All data and records generated during the process of this study will remain confidential in accordance 
with all Institutional and HIPAA policies on subject privacy.  All documents will be used by the 
Investigator and other personnel solely for the purposes of this study.  All safeguards to maintain 
subject confidentiality are described above (5.1 Data Collection and Management).  No information 
will leave Montefiore in the event that an investigator leaves during the duration of the study.   
5.3 Regulatory and Ethical Considerations 
5.3.1 Risk assessment 
Stretta is a safe, non-invasive FDA approved procedure performed endoscopically under moderate 
sedation or general anesthesia which uses radio frequency (RF) energy applied to the lower 
esophagus over 14 minutes per a specific FDA approved protocol and procedure. 
Definition and Reporting of Serious Adverse Events (SAEs) 
A serious adverse event (SAE) is a subtype of adverse event.  An SAE is any adverse event occurring 
when the subject outcome is: 
 
Death 
 
Life-threatening (i.e., subject was at substantial risk of dying at the time of the AE) 
 
Inpatient hospitalization or prolongation of existing hospitalization 
 
Disability or permanent damage 
 
Other serious medical events that jeopardize the health of the subject and require medical or 
surgical intervention such as bronchospasm, blood dyscrasias, seizures/convulsions, or 
development of drug dependency or drug abuse. 
The principal investigator or designee must comply with applicable local regulatory authority and 
IRB/IEC requirements concerning the reporting of SAEs and any safety-related documentation (e.g.., 
safety letters, revised IB) that may be received from the sponsoring entity.  Additionally, the principal 
investigator will keep safety-related documentation in secured site files.  
 
5.3.2 Potential Benefits of Study Participation 
Full resolution or improvement in symptoms related to GERD 
5.3.3 Risk-benefit assessment 
Patients will be undergoing a procedure that is FDA approved and is an acceptable treatment for 
GERD.  This study is intended to collect data and outcomes in the bariatric population. 
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5.4 Informed consent 
 
Informed will be obtained from the subjects directly and not through a health care proxy. Qualified 
interpreter services will be used when appropriate. All risks, benefits, and alternatives of the 
procedure with be explained in detail by study to the participants and supplemental documentation 
will be provided to patients for further review.  
A copy of the Informed Consent document is provided in Appendix 3 
 
5.5 Payment to subjects/families 
No monetary payment will be given to participants. 
6. Statistical Considerations 
 
6.1 Statistical Methods 
Data will be entered on an excel spreadsheet and analyzed with SAS v9.3.  Data analysis will be 
preceded by quality control of our data which will include checks for accuracy, completeness and 
internal validity.  Rates of achievement of 50% reduction of symptoms will be computed and reported 
with their 95% confidence intervals.  Descriptive data analysis will be conducted and all adverse 
events and overall patient characteristics will be described.  The distribution of change in symptom 
scores will be examined and the decrease in patient symptoms will also be examined and described.  
If the distribution of this score approximates normality, symptom reduction will be described using 
mean and standard deviation.  Otherwise we will use median and interquartile ranges.  Bivariate 
analysis will be conducted to examine factors associated with achievement of 50% reduction in 
symptoms.  Categorical variables will be analyzed using the Chi-Square’s exact test.  Continuous 
variables whose distribution meets normality assumptions will be analyzed with the t-test.  Variables 
whose distribution does not approximate normality will be analyzed using the Wilcoxon rank sum 
test.   While we recognize that the sample size is modest – an exploratory multivariate logistic 
regression analysis will be conducted to examine factors associated with 50% symptom reduction  
6.2 Sample Size and Power 
The target number of patients proposed for this protocol is based on our primary objective of 
estimating the proportion of patients achieving at least a 50% reduction of symptoms from baseline as 
measured by RSI and HQRL indices 1 year post treatment.  Sample size calculations are based on this 
primary objective.  Our target sample size is 80 unless perforation occurs in more than 2 patients or 
more than one death directly related to Stretta procedure or the accrual is terminated during interim 
analysis.  A sample size of 50 would produce a two-sided 95% confidence interval with a width of 
0.289 for a proportion of 0.5 and a width of 0.267 for proportions of 0.7.  Taking into consideration 
that given improvement of symptoms or other factorswe estimate a 30% patientsdropout prior to 
completing the 24 month follow-upwe will increase target sample size to a total of 80 patients 
6.3 Patient Accrual  
Patient accrual will begin shortly after approval of protocol at a rate of approximately 10 to 15 
patients per month and estimate patient accrual will be completed 6 months after start of protocol 
 
6.4 Interim analysis and stopping rules:   
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While Stretta has been extensively used safely, we will consider perforation in more than 2 patients or 
more than 1 deaths directly related to Stretta procedure as unacceptable since this rate is higher than 
one would expect from invasive esophageal junction intervention such as dilation. Interim analysis 
will be conducted in an ongoing manner after treatment of eachand every patient, by the principal 
investigator and the lead investigator at each site. If more than 1 patientdiesor more than 2 patients 
suffer perforation attributable to the treatment, we will stop enrolment if no critical adverse events 
occur we will continue accrual to the target sample size of 80 patients.  If a patient suffers a morbid 
event such as perforation or other life threatening event or event that requires surgical intervention 
accrual will be suspend and a through investigation be conducted.  After the root cause is determined 
the study team will confer with the IRB and made a determination as to whether to resume accrual.  If 
there is any event or evidence of increased morbidity form the treatment with the device the 
manufacturer FDA safety information and adverse event program (Medwatch) will be notified.  
7.  Publication 
Once the study is complete and significant conclusions are made, a manuscript will be submitted 
to a relevant journal for publication.   
 
 
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