Esophageal Temperature Dynamics and Injury During Pulmonary Vein Isolation With Temperature Controlled Very-High-Power Short-Duration Lesions Using the Novel Q-DOT Micro Ablation Catheter
Phase: NA
Conditions: Atrial Fibrillation Paroxysmal
Sponsor: Cedars-Sinai Medical Center

 
 
 
 
 
 
Esophageal Temperature Dynamics and Injury During Pulmonary Vein Isolation 
with Temperature-Controlled Very-High-Power Short-Duration Lesions Using the 
Novel Q-DOT Micro Ablation Catheter 
Short Title: Esophageal Temperature During PVI 
Protocol Number: STUDY00002707 
National Clinical Trial (NCT) Identified Number: pending 
Principal Investigator: Eric D Braunstein, MD 
Sponsor: Cedars-Sinai Smidt Heart Institute 
Funded by: Biosense-Webster, Inc. 
Version Number:  1.0 
10 August 2023 
 
Summary of Changes from Previous Version: 
Affected 
Section(s) 
Summary of Revisions Made 
Rationale 
 
 
 
 
 
 

  
Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 2 
1.1 
Synopsis ............................................................................................................................................... 2 
1.2 
Schema ................................................................................................................................................. 3 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 4 
2 
INTRODUCTION ............................................................................................................................................ 5 
2.1 
Study Rationale .................................................................................... Error! Bookmark not defined. 
2.2 
Background .......................................................................................................................................... 5 
2.3 
Risk/Benefit Assessment .................................................................................................................... 5 
2.3.1 
Known Potential Risks .................................................................................................... 5 
2.3.2 
Known Potential Benefits ................................................................................................ 5 
2.3.3 
Assessment of Potential Risks and Benefits ............................................................... 6 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 7 
4 
STUDY DESIGN ............................................................................................................................................ 8 
4.1 
Overall Design ..................................................................................................................................... 8 
4.2 
Scientific Rationale for Study Design ............................................................................................... 8 
4.3 
Justification for Dose ............................................................................ Error! Bookmark not defined. 
4.4 
End of Study Definition ....................................................................................................................... 9 
5 
STUDY POPULATION .................................................................................................................................. 9 
5.1 
Inclusion Criteria .................................................................................................................................. 9 
5.2 
Exclusion Criteria ................................................................................................................................. 9 
5.3 
Lifestyle Considerations ..................................................................................................................... 9 
5.4 
Screen Failures .................................................................................................................................... 9 
5.5 
Strategies for Recruitment and Retention ...................................................................................... 10 
6 
STUDY INTERVENTION ............................................................................................................................ 10 
6.1 
Study Intervention(s) Administration ............................................................................................... 10 
6.1.1 
Study Intervention Description ........................................ Error! Bookmark not defined. 
6.1.2 
Dosing and Administration ............................................... Error! Bookmark not defined. 
6.2 
Preparation/Handling/Storage/Accountability ................................... Error! Bookmark not defined. 
6.2.1 
Acquisition and accountability ......................................... Error! Bookmark not defined. 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ... Error! Bookmark not defined. 
6.2.3 
Product Storage and Stability .......................................... Error! Bookmark not defined. 
6.2.4 
Preparation ........................................................................ Error! Bookmark not defined. 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 11 
6.4 
Study Intervention Compliance ....................................................................................................... 11 
6.5 
Concomitant Therapy ........................................................................... Error! Bookmark not defined. 
6.5.1 
Rescue Medicine .............................................................. Error! Bookmark not defined. 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .................................................................................................................... 11 
7.1 
Discontinuation of Study Intervention ............................................................................................. 11 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 12 
7.3 
Lost to Follow-Up ............................................................................................................................... 12 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 12 
8.1 
Efficacy Assessments ....................................................................................................................... 12 
8.2 
Safety and Other Assessments ....................................................................................................... 12 
8.3 
Adverse Events and Serious Adverse Events ............................................................................... 13 

  
8.3.1 
Definition of Adverse Events (AE) ............................................................................... 13 
8.3.2 
Definition of Serious Adverse Events (SAE) .............................................................. 13 
8.3.3 
Classification of an Adverse Event .............................................................................. 13 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 14 
8.3.5 
Adverse Event Reporting .............................................................................................. 15 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 15 
8.3.7 
Reporting Events to Participants ................................................................................. 15 
8.3.8 
Events of Special Interest ............................................................................................. 15 
8.3.9 
Reporting of Pregnancy ................................................................................................ 15 
8.4 
Unanticipated Problems ................................................................................................................... 15 
8.4.1 
Definition of Unanticipated Problems (UP) ................................................................ 15 
8.4.2 
Unanticipated Problem Reporting ............................................................................... 16 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 16 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 16 
9.1 
Statistical Hypotheses ...................................................................................................................... 16 
9.2 
Sample Size Determination ............................................................................................................. 16 
9.3 
Populations for Analyses .................................................................................................................. 17 
9.4 
Statistical Analyses ........................................................................................................................... 17 
9.4.1 
General Approach .......................................................................................................... 17 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................. 17 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 17 
9.4.4 
Safety Analyses ............................................................................................................. 17 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 17 
9.4.6 
Planned Interim Analyses ............................................................................................. 17 
9.4.7 
Sub-Group Analyses ........................................................ Error! Bookmark not defined. 
9.4.8 
Tabulation of Individual participant Data ....................... Error! Bookmark not defined. 
9.4.9 
Exploratory Analyses ........................................................ Error! Bookmark not defined. 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 17 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 17 
10.1.1 
Informed Consent Process ........................................................................................... 17 
10.1.2 
Study Discontinuation and Closure ............................................................................. 18 
10.1.3 
Confidentiality and Privacy ........................................................................................... 18 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 19 
10.1.5 
Key Roles and Study Governance .............................................................................. 19 
10.1.6 
Safety Oversight ............................................................................................................. 19 
10.1.7 
Clinical Monitoring ......................................................................................................... 19 
10.1.8 
Quality Assurance and Quality Control ....................................................................... 19 
10.1.9 
Data Handling and Record Keeping ........................................................................... 19 
10.1.10 
Protocol Deviations ........................................................................................................ 20 
10.1.11 
Publication and Data Sharing Policy ........................................................................... 20 
10.1.12 
Conflict of Interest Policy .............................................................................................. 21 
10.2 
Additional Considerations ................................................................... Error! Bookmark not defined. 
10.3 
Abbreviations ..................................................................................................................................... 22 
10.4 
Protocol Amendment History ........................................................................................................... 24 
11 
REFERENCES ............................................................................................................................................. 25 
 

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STATEMENT OF COMPLIANCE 
 
The trial will be conducted in accordance with International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), and the Cedars-Sinai 
and Biosense-Webster Terms and Conditions of Award. The Principal Investigator will assure that no 
deviation from, or changes to the protocol will take place without prior agreement from the 
Investigational New Drug (IND) or Investigational Device Exemption (IDE) sponsor, funding agency and 
documented approval from the Institutional Review Board (IRB), except where necessary to eliminate an 
immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study have 
completed Human Subjects Protection and ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will be 
submitted to the IRB for review and approval.  Approval of both the protocol and the consent form must 
be obtained before any participant is enrolled.  Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study.  All changes to the consent form 
will be IRB approved; a determination will be made regarding whether a new consent needs to be 
obtained from participants who provided consent, using a previously approved consent form. 
 
 

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PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Esophageal Temperature Dynamics and Injury During Pulmonary Vein 
Isolation with Temperature-Controlled Very-High-Power Short-Duration 
Lesions Using the Novel Q-DOT Micro Ablation Catheter 
Study Description: 
This is a prospective randomized controlled trial, studying patients 
undergoing ablation involving pulmonary vein isolation for paroxysmal 
atrial fibrillation. Patients will be assigned to undergo conventional high-
power short-duration ablation or temperature-controlled very-high-power 
short-duration ablation, and esophageal outcomes including temperature 
changes during ablation and esophageal injury as assessed by post-
procedure capsule endoscopy will be compared between the groups. The 
hypothesis is that very-high-power short-duration ablation will lead to 
lower rises in esophageal temperature and lower rates of esophageal 
findings during capsule endoscopy. 
Objectives: 
 
Primary objective: To assess for differences in changes in esophageal 
outcomes during posterior wall ablation between the two arms. 
Secondary objectives: To assess for short and long-term procedural 
complications. To assess for procedural efficacy as measured by number of 
lesions, RF time, and procedure time to achieve PVI, and first pass 
pulmonary vein isolation. 
Endpoints: 
Primary endpoint: Maximal change in esophageal temperature during 
posterior wall isolation. 
Secondary endpoints: Presence of esophageal thermal injury seen on post-
procedure capsule endoscopy. Presence of procedural complications, 
number of lesions, RF time, and procedure time to achieve PVI, 
achievement of first pass isolation. 
Study Population: 
Adults aged 18 or more years of age who are undergoing first-time RF 
ablation for paroxysmal atrial fibrillation involving pulmonary vein 
isolation. 
Phase: 
N/a 
Description of 
Sites/Facilities Enrolling 
Participants: 
Patient will be enrolled at Cedars-Sinai Medical Center.  
Description of Study 
Intervention: 
Patients will be randomized to undergo ablation using one of two FDA 
approved ablation catheters (ThermoCool ST SF or QDOT Micro). They will 
undergo esophageal temperature monitoring during the ablation 
procedure using a SensiTherm esophageal temperature probe. 2-4 days 
after the procedure, they will undergo esophageal capsule endoscopy 
using the ANX Robotica NaviCam capsule endoscopy system. 
Study Duration: 
Projected study duration is 12 months. 
Participant Duration: 
3 months. 
 
 

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1.2 
SCHEMA 
 
Prior to  
Enrollment 
 
 
 
 
 
 
 
 
 
 
Visit 1 
 
 
 
 
 
 
Visit 2 
2-4 days 
after ablation 
 
 
 
 
Visit 3 
3 months (90 +- 20) days) 
After ablation 
 
Total screened N=90 for enrollment goal N=30: Obtain informed consent. Screen potential 
participants by inclusion and exclusion criteria; obtain history, document. 
AF Ablation 
Perform baseline assessment and collection of demographic and clinical data. 
Patient will undergo RF catheter ablation for AF involving pulmonary vein isolation (PVI) 
following standard of care. The QDOT Micro or ThermoCool ST SF ablation catheter will 
be used as randomized. Esophageal temperature will be monitored and recording using 
the SensiTherm temperature probe. 
Final Assessment via telephone 
Patient will be contacted via 
telephone and/or chart will be 
reviewed for post-procedural findings 
and assessment of late procedural 
complications. 
Arm 2 – ST SF 
N=15 
Arm 1 – QDOT 
N=15 
Capsule Endoscopy 
2-4 days after the ablation procedure, patients will undergo esophageal capsule 
endoscopy using the ANX Robotics NaviCam system. 
Randomize 

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1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
Procedures 
Screening 
Day -60 to -1 
Enrollment/AF ablation 
Visit 1, Day 0 
Capsule Endoscopy  
Day 2-4 
Final assessment via 
telephone, Day 90+-10 
Informed consent 
X 
 
 
 
Demographics 
X 
 
 
 
Medical history 
X 
 
 
 
Randomization 
X 
 
 
 
AF ablation 
 
X 
 
 
Capsule Endoscopy 
 
 
X 
 
Medication Review 
X 
 
 
 
Adverse event review and 
evaluation 
X 
X 
X 
X 
Complete Case Report Forms 
(CRFs) 
X 
X 
X 
X 
 
 
 

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INTRODUCTION 
 
2.1 
BACKGROUND  
Atrioesophageal fistula is a rare but life-threatening complication of ablation for atrial 
fibrillation, and is primarily caused by thermal injury to the esophagus as a result of posterior left atrial 
ablation in close proximity to the esophagus. Esophageal temperature monitoring is frequently used to 
monitor risk of thermal injury to the esophagus, and although esophageal temperature monitoring has 
not been shown to reduce the risk of esophageal injury directly,1,2 observational studies have shown 
that the degree of esophageal temperature rise does correlate to the severity of esophageal thermal 
injury.3,4 A variety of methods have been studied to prevent esophageal injury, including high-power 
short duration lesions,5,6 esophageal deviation,7 closed loop esophageal cooling,8 and positioning of 
ablation lesions to avoid the esophagus on multimodality imaging,9 all with variable success. 
 
Given the ongoing interest in high-power, short-duration ablation to improve safety and reduce 
procedure times, the Q-DOT Micro ablation catheter (Biosense Webster, Inc.) has recently been 
developed with the ability to deliver temperature-controlled, very-high-power (up to 90W), short-
duration RF ablation lesions. Initial studies of the catheter have shown clinical feasibility, efficacy, and 
safety.10,11 More recent studies including the Q-FFICIENCY12 trial and POWER PLUS13 trial have 
demonstrated comparable efficacy, reduced procedures times, and complication rates comparable to 
other catheters. 
To date, detailed analysis of esophageal temperature dynamics and subsequent risk for 
esophageal injury during posterior wall ablation for AF ablation using temperature-controlled very-high-
power, short-duration ablation with the Q-DOT Micro catheter as compared with conventional ablation 
catheters has not been fully assessed. 
 
2.2 
RISK/BENEFIT ASSESSMENT   
 
2.2.1 KNOWN POTENTIAL RISKS  
All invasive ablation procedures have risk. We do not anticipate additional ablation procedural risks 
stemming from participation in this study, as standard of care will be followed and only FDA approved 
medical devices are to be used. 
 
In addition to standard of care, capsule endoscopy will be performed as part of this study. Although 
capsule endoscopy is a very safe procedure, there is a small risk of capsule retention and bowel 
obstruction that could necessitate a procedure or surgery to remove the capsule. 
 
There is a small risk that patient information could be released unintentionally to unauthorized 
personnel. As noted above, this risk will be minimized by storing patient information in a secure, 
password-protected database and using a linking code for demographic information; only the principal 
investigator and co-investigators will have access to the databases. 
 
2.2.2 KNOWN POTENTIAL BENEFITS  

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We do not anticipate any personal benefits from participation in this trial. 
 
2.2.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
Participation in this trial will only involve small risks, the primary increased risk being capsule endoscopy. 
This test is necessary as one of the main endpoints of the trial is esophageal injury that needs to be 
assessed with endoscopy. Capsule endoscopy was chosen rather than convention endoscopy or nasal 
endoscopy to minimize subject risk.  
 
 

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3 
OBJECTIVES AND ENDPOINTS 
The overall objective of the study is to study the effect of different ablation power strategies on esophageal 
temperatures during posterior wall RF ablation during catheter ablation for paroxysmal atrial fibrillation involving 
pulmonary vein isolation. This prospective study will compare esophageal temperatures during conventional high-
power short-duration ablation to temperature-controlled very-high-power short-duration ablation using the novel 
Q-DOT Micro catheter. 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
To assess esophageal temperature 
dynamics during AF ablation using 
two different ablation catheters 
during ablation of the posterior 
wall. 
Change in esophageal temperature 
during posterior wall ablation, 
defined by maximal temperature 
minus baseline esophageal 
temperature before the start of 
posterior wall ablation, as well as 
time to maximal esophageal 
temperature after start of ablation 
lesions. 
Very-high power short 
duration lesions may 
lead to lower increases 
in esophageal 
temperature due to a 
different balance of 
resistive vs conductive 
heating during RF 
ablation. 
Secondary 
 
 
To assess for esophageal thermal 
injury after AF ablation when using 
two different ablation catheters 
during ablation of the posterior 
wall. 
Presence of stigmata of esophageal 
thermal injury as assessed by capsule 
endoscopy performed 2-4 days after 
the ablation procedure. 
Very-high power short 
duration lesions may 
lead to less esophageal 
thermal injury, again 
due to a different 
balance of resistive vs 
conductive heating 
leading to less far field 
heating. 
To assess for post-procedural 
complications related to 
esophageal thermal injury. 
Presence of procedural complications 
related to esophageal injury including 
atrial-esophageal (AE) fistula, as 
assess at 90 day follow-up via chart 
review and/or telephone follow-up. 
The most serious 
complication of 
esophageal thermal 
injury is AE fistula, a 
rare but life-
threatening 
complication of AF 
ablation. Though we do 
not expect any 
instances of this during 
the study, it will be 
important to assess for. 
To assess for ablation acute 
procedural efficacy. 
Acute procedural efficacy as assessed 
by number of lesions, RF time, and 
procedure time to achieve PVI, and 
achievement of first pass isolation. 
Very-high power short 
duration lesions may 
lead to increased 
procedural efficacy and 
shorter procedure 
times. 
 

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4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
A randomized, prospective, open-label, post-market, single-site, pilot study trial of patients undergoing 
first-time RF ablation involving pulmonary vein isolation for treatment of paroxysmal atrial fibrillation at 
a single center will be performed to assess for differences in esophageal temperature dynamics and 
thermal injury using two different ablation catheters, as well as post procedural complications and 
outcomes of acute procedural efficacy. 
 
After obtaining consent, patients will be assigned to undergo ablation using either a high-power short-
duration ablation strategy (40-50W, ST SF arm) or a temperature-controlled, very-high-power (up to 
90W), short-duration ablation strategy (QDOT arm). During posterior wall ablation, esophageal 
temperatures will be monitored using a multipolar temperature monitoring probe (Abbott SensiTherm). 
Post-procedurally, patients will undergo esophageal capsule endoscopy to assess for evidence of 
thermal injury to the esophagus. Patient will then undergo 90-day follow-up via chart review and/or 
telephone call to assess for post-procedural complications, particularly related to esophageal thermal 
injury. 
 
We hypothesize that patient undergoing temperature-controlled very-high-power short-duration 
ablation will have less esophageal heating and thermal injury as compared to high-power short-
duration. 
 
Patients will be recruited to the study and informed consent will be obtained. 
 
Electronic case report forms (CRFs) will be completed which will collect data on demographic and clinical 
characteristics including: patient MRN, age, sex, date of birth, race/ethnicity, date of procedure, type of 
arrhythmia and proposed treatment strategy, medications at the time of enrollment, relevant 
laboratory data including serum Na, K, creatinine, Mg, Hgb, pro-BNP, echocardiographic measurements 
including left ventricular ejection fraction and size and left atrial size, and medical history including 
history of cardiac conditions (i.e. coronary artery disease, heart failure, arrhythmias) and other relevant 
medical history. 
 
A linking code will be used for the demographic information above to minimize the risk of inadvertent 
release of PHI during the study. 
 
The data for the prospective study will be obtained over 12 months with a goal to enroll 30 patients.  
 
Patients will be followed for three months post-procedurally primarily to assess for late procedural 
complications (e.g. atrioesophageal fistula). This will be done through chart review of the EMR, and/or 
telephone calls to study participants if needed. 
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
This study is designed as a randomized open-label device trial. Currently, the differences in esophageal 
temperature between the two ablation strategies is not known. Due to differences in the ablation 
catheter design and use, it would be impractical for the study to be blinded. We are aiming to show that 
the intervention (QDOT) arm is superior, so therefore a non-inferiority design would not be appropriate. 

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4.3 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed the ablation 
procedure and capsule endoscopy, and completed 90-day follow-up via chart-review and/or telephone. 
 
The end of the study is defined as completion of the last visit or procedure shown in the SoA in the trial 
globally. 
 
5 
STUDY POPULATION 
This study will enroll 30 patients undergoing first-time RF catheter ablation for treatment of paroxysmal 
atrial fibrillation that will involve pulmonary vein isolation (PVI) and meet the inclusion and exclusion 
criteria for participation in this study. 
 
5.1 
INCLUSION CRITERIA 
In order to be eligible to participate in this study, an individual must meet all of the following criteria: 
 
1. Provision of signed and dated informed consent form 
2. Stated willingness to comply with all study procedures and availability for the duration of the 
study 
3. Male or female, aged greater than or equal to 18 years 
4. Diagnosed with paroxysmal atrial fibrillation 
5. Undergoing RF catheter ablation for treatment of paroxysmal atrial fibrillation that will involve 
circumferential point-by-point radiofrequency ablation pulmonary vein isolation with no 
additional left atrial posterior wall ablation planned 
 
5.2 
EXCLUSION CRITERIA 
An individual who meets any of the following criteria will be excluded from participation in this study: 
1. Patients who have undergone prior left atrial ablation procedures. 
2. Patients where the use of the Q-DOT Micro ablation catheter in QMODE+ (i.e. temperature-
controlled very-high-power short-duration ablation) is felt to be unsafe. 
3. Patients who have contraindications to capsule endoscopy, or GI conditions that may increase 
the risks of capsule endoscopy (e.g. esophageal strictures, inflammatory bowel disease, etc) 
4. Any records flagged “break the glass” or “research opt out.” 
5.3 
LIFESTYLE CONSIDERATIONS 
No lifestyle considerations are anticipated for participation in this study. 
 
5.4 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in the clinical trial but are not 
subsequently randomly assigned to the study intervention or entered in the study. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure participants, to 
meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, screen 
failure details, eligibility criteria, and any serious adverse event (SAE). 

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5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
This study will enroll 30 patients total, and we anticipate 90 patients will need to be screened to enroll 
this number. The projected study duration will be 12 months, and therefore we expect to screen 6-10 
patients and enroll 2-3 patients per month. This is feasible based on the number of AF ablation 
performed at the medical center per month. 
 
AF ablation is primarily performed as an outpatient/ambulatory procedure, and therefore the subjects 
will be enrolled based on referrals from faculty electrophysiologists and review of faculty 
electrophysiologists’ schedules for patients undergoing AF ablation. They will be screened over the 
phone by study staff, and informed consent and the baseline visit will be done at the time of the AF 
ablation procedure. 
 
Participants will be given a $100 incentive stipend for participation in this study, to help cover additional 
costs that may be accrued as a result of undergoing capsule endoscopy (travel, parking, etc.). 
 
6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION ADMINISTRATION 
 
6.1.1 ABLATION PROCEDURE 
 
Enrolled patients will undergo RF catheter ablation for treatment of paroxysmal atrial fibrillation 
following standard of care. Circumferential point-by-point radiofrequency pulmonary vein isolation will 
be performed for all patients, with additional lesions sets (e.g. cavo-tricuspid isthmus ablation) made at 
the discretion of the operator. Patient should not be planned to undergo additional posterior wall 
ablation outside of ablation required for PVI. Patients will be assigned to undergo ablation with one of 
two ablation strategies assigned for posterior wall ablation during PVI: a high-power short-duration 
ablation strategy using the ThermoCool SmartTouch SF ablation catheter (ST SF arm), or a temperature-
controlled, very-high-power short-duration ablation strategy using the QDOT Micro ablation catheter 
(QDOT arm). 
 
For the ST SF arm, ablation on the posterior wall will be performed using a power of 40 to 50W, with 
ablation duration at the discretion of the operator. Ablation endpoints including but not limited to 
ablation time, impedance changes, and Visitag Surpoint tag index may be used. 
 
For the QDOT arm, ablation on the posterior wall will be performed in the QMODE+ mode, with 
temperature-controlled ablation lesions delivered at a maximum of 90W for 4 seconds. 
 
The Biosense Webster Carto3 system will be used for electroanatomic mapping. 3 mm Visitags will be 
used for ablation lesions. Esophageal temperature monitoring will be performed using a multipolar 
temperature probe (Abbott SensiTherm). Baseline esophageal temperature will be recorded just prior to 
the start of posterior wall ablation based on the pole with the highest temperature, and the peak 
temperature during each posterior wall ablation lesion will be recorded also based on the pole with the 
highest temperature. Time to peak temperature after each ablation lesions will be recorded. Full 
esophageal temperature data/plots (maximum and from each pole) will be exported from the 

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SensiTherm console at the completion of the case for additional analyses. During ablation lesions where 
temperature rises >1° C are seen, the operator will be instructed to wait for the temperature to return 
to within 1° C of baseline or wait 60 seconds before performing another lesion within 10 mm of this 
lesion on the posterior wall. Fluoroscopy and electroanatomic mapping will be used to ensure the 
ablation catheter and temperature probe are in sufficient vertical proximity. Additional fluoroscopic 
images will be taken in RAO 45 and LAO 45 views to allow for post-procedure 3D reconstruction of the 
distance between the ablation catheter and the temperature probe. Additional data will be collected on 
acute procedural outcomes including number of lesions and RF time to achieve PVI, procedure duration, 
achievement of first pass isolation in each set of pulmonary veins (adjudicated by the operator), and 
presence of acute procedural complications. 
 
All patients will be prescribed a daily proton-pump inhibitor (if they are not already taking or 
contraindicated) per usual protocol after RF AF ablation. 
 
6.1.2 POST-PROCEDURE CAPSULE ENDOSCOPY 
 
Patient will undergo esophageal capsule endoscopy using the ANX Robotica NaviCam system 2-4 days 
after the ablation procedure. The capsule endoscopy will be interpreted by gastroenterologists with 
expertise in capsule endoscopy, who will be blinded to the ablation treatment strategy used. 
 
6.2 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
The study will be randomized in a 1:1 fashion between the two study groups. Due to differences in the 
operation of the two different ablation catheters being compared, the trial will be open label and no 
blinding will be performed, with the exception of the blinding of the interpreters of the capsule 
endoscopy who will be blinded to the ablation strategy used. 
 
6.3 
STUDY INTERVENTION COMPLIANCE 
Informed consent will be obtained from patients at the start of the study, with particular attention to 
ensure compliance with the post-procedure capsule endoscopy and 90-day follow-up. 
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
If at any time during the ablation procedure use of the randomized ablation catheter is felt to be unsafe 
or suboptimal by the operator, use of the catheter can be discontinued. Discontinuation from the 
randomized ablation catheter does not mean discontinuation from the study, and remaining study 
procedures should be completed as indicated by the study protocol.  If a clinically significant finding is 
identified (including, but not limited to changes from baseline) after enrollment, the investigator or 
qualified designee will determine if any change in participant management is needed. Any new clinically 
relevant finding will be reported as an adverse event (AE). 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
• 
Reason for discontinuation from the study 
• 
Relevant temperature and other procedural parameters 
 

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7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Participants are free to withdraw from participation in the study at any time upon request. 
An investigator may discontinue or withdraw a participant from the study for the following reasons: 
 
• 
Significant study intervention non-compliance (e.g. failure to complete capsule endoscopy) 
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
Disease progression which requires discontinuation of the study intervention (e.g. progression 
to persistent atrial fibrillation before the ablation procedure) 
• 
If the participant meets an exclusion criterion (either newly developed or not previously 
recognized) that precludes further study participation 
The reason for participant discontinuation or withdrawal from the study will be recorded on the Case 
Report Form (CRF). Subjects who sign the informed consent form and are randomized but do not receive 
the study intervention may be replaced. Subjects who sign the informed consent form, and are 
randomized and receive the study intervention, and subsequently withdraw, or are withdrawn or 
discontinued from the study, will also be replaced. 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for the capsule endoscopy 
and is unable to be contacted by the study site staff. 
 
The following actions must be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit within the 2-4 
day post-procedural time-frame, and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain if the participant wishes to and/or should continue in 
the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls). These contact 
attempts should be documented in the participant’s medical record or study file. 
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
EFFICACY ASSESSMENTS  
As described above, the efficacy assessments for the study will be the primary and secondary endpoints: 
changes in esophageal temperature during posterior wall ablation, stigmata of esophageal thermal 
injury on capsule endoscopy, presence of post-procedural complications particularly related to 
esophageal thermal injury, and measures of acute procedural efficacy. 
 
8.2 
SAFETY AND OTHER ASSESSMENTS 
 

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Presence of procedural complications will be assessed and recording in each subject’s chart. 
  
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.3.1 DEFINITION OF ADVERSE EVENTS (AE) 
Adverse event means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)).] 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the participant and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or drug abuse. 
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 SEVERITY OF EVENT 
For adverse events (AEs) not included in the protocol defined grading system, the following guidelines 
will be used to describe severity.  
 
• 
Mild – Events require minimal or no treatment and do not interfere with the participant’s daily 
activities.  
• 
Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning. 
• 
Severe – Events interrupt a participant’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually potentially life-threatening or 
incapacitating.  Of note, the term “severe” does not necessarily equate to “serious”.] 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
All adverse events (AEs) must have their relationship to study intervention assessed by the clinician who 
examines and evaluates the participant based on temporal relationship and his/her clinical judgment. 
The degree of certainty about causality will be graded using the categories below. In a clinical trial, the 
study product must always be suspect.  
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study intervention administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study intervention (dechallenge) should be clinically plausible. The event must be 

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pharmacologically or phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within 
a reasonable time after administration of the study intervention, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal (dechallenge). Rechallenge information is not required to fulfill this definition. 
• 
Potentially Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial medication). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 
concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study intervention administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after administration of the 
study intervention) and in which other drugs or chemicals or underlying disease provides 
plausible explanations (e.g., the participant’s clinical condition, other concomitant treatments). 
• 
Not Related – The AE is completely independent of study intervention administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician. 
 
8.3.3.3 EXPECTEDNESS  
The principal investigator will be responsible for determining whether an adverse event (AE) is expected 
or unexpected.  An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study intervention. 
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All AEs 
occurring while on study must be documented appropriately regardless of relationship. All AEs will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. AEs characterized as intermittent require documentation of 
onset and duration of each episode. 
 

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The principal investigator will record all reportable events with start dates occurring any time after 
informed consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day of 
study participation.  At each study visit, the investigator will inquire about the occurrence of AE/SAEs 
since the last visit.  Events will be followed for outcome information until resolution or stabilization. 
 
8.3.5 ADVERSE EVENT REPORTING  
All adverse events occurring on this study will be reported to the IRB according to the IRB policy. 
 
8.3.6 SERIOUS ADVERSE EVENT REPORTING  
The study investigator shall submit notification of the serious adverse event to the study sponsor and to 
the reviewing Institutional Review Board (IRB) as soon as possible, but in no event later than 10 working 
days after the investigator first learns of the effect. 
 
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
Study-related adverse events will be reported to the individual study participant who undergoes the 
adverse event as soon as it is recognized by the study staff. 
 
8.3.8 EVENTS OF SPECIAL INTEREST  
Not applicable. 
 
8.3.9 REPORTING OF PREGNANCY  
Not applicated. 
 
8.4 
UNANTICIPATED PROBLEMS 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
This definition could include an unanticipated adverse device effect, any serious adverse effect on 
health or safety or any life-threatening problem or death caused by, or associated with, a device, if that 
effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects (21 CFR 812.3(s)). 

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8.4.2  UNANTICIPATED PROBLEM REPORTING  
The investigator will report unanticipated problems (UPs) to the reviewing Institutional Review Board 
(IRB) and to the Data Coordinating Center (DCC)/lead principal investigator (PI). The UP report will 
include the following information: 
 
• 
Protocol identifying information: protocol title and number, PI’s name, and the IRB project 
number; 
• 
A detailed description of the event, incident, experience, or outcome;  
• 
An explanation of the basis for determining that the event, incident, experience, or outcome 
represents an UP;  
• 
A description of any changes to the protocol or other corrective actions that have been taken or 
are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the following timeline:   
 
• 
UPs that are serious adverse events (SAEs) will be reported to the IRB and to the DCC/study 
sponsor within 10 days of the investigator becoming aware of the event.  
• 
Any other UP will be reported to the IRB and to the DCC/study sponsor within 10 days of the 
investigator becoming aware of the problem.  
• 
All UPs should be reported to appropriate institutional officials (as required by an institution’s 
written reporting procedures), the supporting agency head (or designee), and the Office for 
Human Research Protections (OHRP) within 10 days of the IRB’s receipt of the report of the 
problem from the investigator. 
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
Not applicable. 
 
9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STATISTICAL HYPOTHESES 
Primary Efficacy Endpoint: The first primary endpoint will be esophageal temperature dynamics during 
AF ablation, which will be measured by a multipolar esophageal temperature probe. We hypothesize 
that temperature-controlled very-high-power short-duration ablation will result in smaller increases in 
esophageal temperature during ablation. 
 
Secondary Efficacy Endpoint 1: The second primary endpoint will be esophageal thermal injury after AF 
ablation, which will be measured by assessing for stigmata of esophageal thermal injury on post-
procedure capsule endoscopy. 
 
Secondary Efficacy Endpoint 2: The secondary endpoint will be post-procedural complications related to 
esophageal thermal injury. We do not anticipate any events will occur during the trial as these are very 
rare, but these events will be assessed for. 
 
9.2 
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Sample size determination was based on power calculations for a 75% power. This was based on a 1 
degree difference in the primary outcome defined as a significant effect. The estimated standard 
deviation of change in temperature is 1 degree based on review of prior procedures; therefore, the 
effect size is approximately 1. Using a standard 2-sided alpha of 0.05, a sample size of 30 provides 75% 
power. 
 
9.3 
POPULATIONS FOR ANALYSES 
Though we anticipate a low-risk of any crossover occurring during the study, if crossover does occur 
then the analysis will be performed using intention-to-treat analysis. 
 
9.4 
STATISTICAL ANALYSES 
9.4.1 GENERAL APPROACH 
All continuous data will be expressed as mean ± SD or median (IQR) depending on normality of 
distribution and compared using Student’s t-test or the Wilcoxon Rank-Sum test as appropriate. 
 
Categorical data will be expressed as n (%) and compared using Fisher’s exact test. 
 
9.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
Univariate analysis of the primary endpoints will be performed using Student’s t-test and Fisher’s exact 
test. Linear regression for the primary endpoint will be used to assess for confounding risk factors. 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Secondary endpoints will be compared between the groups using t-tests and Fisher’s exact test as 
appropriate. Multiple logistic regression will be performed for presence of stigmata of esophageal 
thermal injury with potential confounding risk factors. 
 
9.4.4 SAFETY ANALYSES 
Not applicable. 
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
Not applicable. 
 
9.4.6 PLANNED INTERIM ANALYSES  
Not applicable. 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
Consent forms describing in detail the study intervention, study procedures, and risks are given to the 
participant and written documentation of informed consent is required prior to starting 

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intervention/administering study intervention.  The following consent materials are submitted with this 
protocol: Informed consent form. 
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Consent forms will be Institutional 
Review Board (IRB)-approved and the participant will be asked to read and review the document. The 
investigator will explain the research study to the participant and answer any questions that may arise. 
A verbal explanation will be provided in terms suited to the participant’s comprehension of the 
purposes, procedures, and potential risks of the study and of their rights as research participants.  
Participants will have the opportunity to carefully review the written consent form and ask questions 
prior to signing. The participants should have the opportunity to discuss the study with their family or 
surrogates or think about it prior to agreeing to participate. The participant will sign the informed 
consent document prior to any procedures being done specifically for the study. Participants must be 
informed that participation is voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the participants for their records. 
The informed consent process will be conducted and documented in the source document (including the 
date), and the form signed, before the participant undergoes any study-specific procedures. The rights 
and welfare of the participants will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to <study participants, investigator, funding agency, 
the Investigational New Drug (IND) or Investigational Device Exemption (IDE) sponsor and regulatory 
authorities>.  If the study is prematurely terminated or suspended, the Principal Investigator (PI) will 
promptly inform study participants, the Institutional Review Board (IRB), and sponsor and will provide 
the reason(s) for the termination or suspension.  Study participants will be contacted, as applicable, and 
be informed of changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the sponsor, IRB and/or Food and Drug Administration (FDA). 
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover testing of 
biological samples and genetic tests in addition to the clinical information relating to participants. 

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Therefore, the study protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released to any unauthorized 
third party without prior written approval of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), regulatory agencies or pharmaceutical company supplying study product may 
inspect all documents and records required to be maintained by the investigator, including but not 
limited to, medical records (office, clinic, or hospital) and pharmacy records for the participants in this 
study. The clinical study team will permit access to such records. 
 
The study participant’s contact information will be securely stored for internal use during the study. At 
the end of the study, all records will continue to be kept in a secure location for as long a period as 
dictated by the reviewing IRB, Institutional policies, or sponsor requirements. 
 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
Not applicable. 
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
Principal Investigator/Medical 
Monitor 
Eric D Braunstein, MD 
Cedars-Sinai Smidt Heart Institute  
127 S San Vicente Blvd, Suite A3600 
310-248-6679 
Eric.Braunstein@cshs.org 
 
 
10.1.6 SAFETY OVERSIGHT 
As all devices and interventions being used in the study are FDA approved and in routine clinical use, 
safety oversight for the study will be performed by the principal investigator. 
 
10.1.7 CLINICAL MONITORING 
Not applicable. 
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Not applicable. 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the site 
investigator. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported. 
 

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All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.   
 
Hardcopies of the study visit worksheets will be provided for use as source document worksheets for 
recording data for each participant enrolled in the study.  Data recorded in the electronic case report 
form (eCRF) derived from source documents should be consistent with the data recorded on the source 
documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and expected adverse reactions 
data) and clinical laboratory data will be entered into RedCap, a 21 CFR Part 11-compliant data capture 
system. The data system includes password protection and internal quality checks, such as automatic 
range checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will be 
entered directly from the source documents. 
 
10.1.9.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 2 years after the last approval of a marketing 
application in an International Conference on Harminosation (ICH) region and until there are no pending 
or contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations. No records will be destroyed 
without the written consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform 
the investigator when these documents no longer need to be retained. 
 
10.1.10 
PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations within 10 working days of identification of the protocol deviation, or within 10 working days 
of the scheduled protocol-required activity.  All deviations must be addressed in study source 
documents, reported to the principal investigator.  Protocol deviations must be sent to the reviewing 
Institutional Review Board (IRB) per their policies. The site investigator is responsible for knowing and 
adhering to the reviewing IRB requirements. Further details about the handling of protocol deviations 
will be included in the MOP. 
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 

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This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-
reviewed journals. Data from this study may be requested from other researchers 2 years after the 
completion of the primary endpoint by contacting principal investigator. 
 
 
10.1.12 
CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical.  Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial.  The study 
leadership has established policies and procedures for all study group members to disclose all conflicts 
of interest and will establish a mechanism for the management of all reported dualities of interest. 

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10.2 ABBREVIATIONS 
The list below includes abbreviations utilized in this template.  However, this list should be customized for 
each protocol (i.e., abbreviations not used should be removed and new abbreviations used should be 
added to this list). 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS 
Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 

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SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10.3 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11 REFERENCES  
1. 
Chen S, Schmidt B, Seeger A, et al. Catheter ablation of atrial fibrillation using ablation index–guided high 
power (50 W) for pulmonary vein isolation with or without esophageal temperature probe (the AI-HP ESO 
II). Heart Rhythm. 2020;17(11):1833-1840. doi:10.1016/J.HRTHM.2020.05.029 
2. 
Schoene K, Arya A, Grashoff F, et al. Oesophageal Probe Evaluation in Radiofrequency Ablation of Atrial 
Fibrillation (OPERA): results from a prospective randomized trial. EP Europace. 2020;22(10):1487-1494. 
doi:10.1093/EUROPACE/EUAA209 
3. 
Leung LWM, Akhtar Z, Sheppard MN, Louis-Auguste J, Hayat J, Gallagher MM. Preventing esophageal 
complications from atrial fibrillation ablation: A review. Heart Rhythm O2. 2021;2(6):651-664. 
doi:10.1016/J.HROO.2021.09.004 
4. 
Kadado AJ, Akar JG, Hummel JP. Luminal esophageal temperature monitoring to reduce esophageal 
thermal injury during catheter ablation for atrial fibrillation: A review. Trends Cardiovasc Med. 
2019;29(5):264-271. doi:10.1016/J.TCM.2018.09.010 
5. 
Barbhaiya CR, Kogan E v., Jankelson L, et al. Esophageal temperature dynamics during high-power short-
duration posterior wall ablation. Heart Rhythm. 2020;17(5):721-727. doi:10.1016/J.HRTHM.2020.01.014 
6. 
Chen S, Chun KRJ, Tohoku S, et al. Esophageal Endoscopy After Catheter Ablation of Atrial Fibrillation Using 
Ablation-Index Guided High-Power: Frankfurt AI-HP ESO-I. JACC Clin Electrophysiol. 2020;6(10):1253-1261. 
doi:10.1016/J.JACEP.2020.05.022 
7. 
Parikh V, Swarup V, Hantla J, et al. Feasibility, safety, and efficacy of a novel preshaped nitinol esophageal 
deviator to successfully deflect the esophagus and ablate left atrium without esophageal temperature rise 
during atrial fibrillation ablation: The DEFLECT GUT study. Heart Rhythm. 2018;15(9):1321-1327. 
doi:10.1016/J.HRTHM.2018.04.017 
8. 
Zagrodzky J, Gallagher MM, Leung LWM, et al. Cooling or Warming the Esophagus to Reduce Esophageal 
Injury During Left Atrial Ablation in the Treatment of Atrial Fibrillation. J Vis Exp. 2020;2020(157). 
doi:10.3791/60733 
9. 
Teres C, Soto-Iglesias D, Penela D, et al. Relationship between the posterior atrial wall and the esophagus: 
esophageal position and temperature measurement during atrial fibrillation ablation (AWESOME-AF). A 
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