Esophageal Temperature Management During Cryo AF Ablation
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Northwestern University

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Utility of Esophageal Temperature Management for the Prevention of 
Thermal Injury During Cryoballoon Ablation for Atrial Fibrillation
Principal Investigator 
Nishant Verma, MD, MPH
Co-Principal Investigator
Bradley P. Knight, MD
Funding Sponsor 
Attune Medical
3440 S. Dearborn St, Suite 215-S
Chicago, IL 60616
888-534-4873
info@attune-medical.com 
Study Device:
Attune Medical Esophageal Heat Transfer Device - 
EnsoETM 
IRB Protocol Number:
STU00209610 
Protocol Version:  1.0 (03/AUG/2019)
Amended
2.0 (25OCT/2019)
Amended
3.0 [23Jun2020]
IRB #: STU00209610-MOD0003 Approved by NU IRB for use on or after 7/6/2020 through 6/7/2021.

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Table of Contents
LIST OF ABBREVIATIONS........................................................................................................................IV
STUDY SUMMARY......................................................................................................................................V
1.0 BACKGROUND AND STUDY RATIONALE .........................................................................................1
1.1
INTRODUCTION ...........................................................................................................................................1
1.2
BACKGROUND AND RELEVANT LITERATURE..................................................................................................1
1.3
NAME AND DESCRIPTION OF THE STUDY DEVICE ..........................................................................................1
1.3.1
Nonclinical Data ...................................................................................................................................1
1.3.2
Clinical Data to Date ............................................................................................................................2
2
STUDY OBJECTIVES .........................................................................................................................2
2.1
PRIMARY OBJECTIVES.................................................................................................................................2
2.2
SECONDARY OBJECTIVES ...........................................................................................................................2
3
INVESTIGATIONAL PLAN..................................................................................................................2
3.1
GENERAL DESIGN.......................................................................................................................................2
3.1.1
Screening Phase..................................................................................................................................2
3.1.2
Study Intervention Phase.....................................................................................................................2
3.1.3
Follow Up Visit (Day 60 ±14 days).......................................................................................................3
3.1.4
Follow Up Data Collection Phase.........................................................................................................3
3.1.5
Randomization .....................................................................................................................................3
3.2
STUDY ENDPOINTS .....................................................................................................................................4
3.2.1
Primary Study Endpoints......................................................................................................................4
3.2.2
Secondary Study Endpoints.................................................................................................................4
3.2.3
Primary Safety Endpoints.....................................................................................................................4
4
STUDY POPULATION AND DURATION OF PARTICIPATION.........................................................4
4.1
INCLUSION CRITERIA...................................................................................................................................4
4.2
EXCLUSION CRITERIA..................................................................................................................................4
4.3
SUBJECT RECRUITMENT..............................................................................................................................4
4.4
DURATION OF STUDY PARTICIPATION...........................................................................................................4
4.5
TOTAL NUMBER OF SUBJECTS AND SITES ....................................................................................................5
5
STUDY INTERVENTION .....................................................................................................................5
5.1
DEVICE DESCRIPTION .................................................................................................................................5
5.2
INTERVENTION REGIMEN .............................................................................................................................5
5.3
STORAGE...................................................................................................................................................5
5.4
PREPARATION AND PACKAGING & SUPPLY ...................................................................................................5
5.5
BLINDING ...................................................................................................................................................5
5.6
DEVICE ACCOUNTABILITY............................................................................................................................5
6
SCHEDULE OF STUDY VISITS, PROCEDURES, AND DATA EXTRACTION .................................6
6.1
PRE-SCREENING ........................................................................................................................................6
6.2
STUDY VISITS & DATA COLLECTION.............................................................................................................6
6.2.1
Visit 1/Day 0 (Screening, Enrollment, Randomization, and Ablation) ..................................................6
6.2.2
Visit 2 (Post-op day 1)..........................................................................................................................7
6.2.3
Visit 3 (Post ablation Month 2) .............................................................................................................7
6.2.4
Follow up data collection (Post ablation Month 3,6,12)........................................................................8
6.3
RESCUE THERAPY ......................................................................................................................................8
6.4
UNSCHEDULED VISITS.................................................................................................................................8
6.5
SUBJECT WITHDRAWAL...............................................................................................................................8
6.5.1
Data Collection and Follow-up for Withdrawn Subjects .......................................................................8
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7
STATISTICAL PLAN...........................................................................................................................8
PRIMARY ENDPOINT.................................................................................................................................................8
7.1
SECONDARY ENDPOINTS.............................................................................................................................9
7.2
SAMPLE SIZE AND POWER DETERMINATION .................................................................................................9
7.3
STATISTICAL METHODS...............................................................................................................................9
7.3.1
Baseline Data.......................................................................................................................................9
7.3.2
Efficacy Analysis ..................................................................................................................................9
7.3.3
Interim Safety Analysis.........................................................................................................................9
7.4
SUBJECT POPULATION(S) FOR ANALYSIS .....................................................................................................9
8
SAFETY AND ADVERSE EVENTS ....................................................................................................9
8.1
DEFINITIONS...............................................................................................................................................9
8.1.1
Unanticipated Adverse Device Effect...................................................................................................9
8.1.2
Adverse Event....................................................................................................................................10
8.1.3
Serious Adverse Event.......................................................................................................................10
8.1.4
Unanticipated Problems(UP) Involving Risk to Subjects or Others....................................................10
8.1.5
Preexisting Condition .........................................................................................................................10
8.1.6
General Physical Examination Findings.............................................................................................11
8.1.7
Post-study Adverse Event..................................................................................................................11
8.1.8
Hospitalization, Prolonged Hospitalization or Surgery .......................................................................11
8.2
RECORDING OF ADVERSE EVENTS.............................................................................................................11
8.3
CLASSIFICATION OF ADVERSE EVENTS.......................................................................................................11
8.4
ADVERSE EVENT REPORTING PERIOD........................................................................................................12
8.5
EXPEDITED REPORTING OF EVENTS...........................................................................................................12
8.5.1
Follow-up report .................................................................................................................................12
8.5.2
Sponsor reporting: Notifying the Funding Sponsor ............................................................................13
8.6
UNBLINDING PROCEDURES........................................................................................................................13
8.7
DATA AND SAFETY MONITORING................................................................................................................13
9
STUDY ADMINISTRATION, DATA HANDLING AND RECORD KEEPING ....................................13
9.1
CONFIDENTIALITY .....................................................................................................................................13
9.2
DATA COLLECTION AND MANAGEMENT.......................................................................................................13
9.3
RECORDS RETENTION...............................................................................................................................14
10
STUDY MONITORING, AUDITING, AND INSPECTING ..................................................................14
10.1
STUDY MONITORING PLAN ........................................................................................................................14
10.2
AUDITING AND INSPECTING........................................................................................................................14
11
ETHICAL CONSIDERATIONS..........................................................................................................14
11.1
RISKS ......................................................................................................................................................14
11.2
BENEFITS.................................................................................................................................................15
11.3
RISK BENEFIT ASSESSMENT......................................................................................................................15
11.4
INFORMED CONSENT PROCESS / HIPAA AUTHORIZATION...........................................................................15
11.5
ELECTRONIC CONSENT.............................................................................................................................15
12
STUDY FINANCES............................................................................................................................16
12.1
FUNDING SOURCE ....................................................................................................................................16
12.2
CONFLICT OF INTEREST.............................................................................................................................16
12.3
PARTICIPANT STIPENDS OR PAYMENTS......................................................................................................16
13
PUBLICATION PLAN........................................................................................................................16
14
REFERENCES...................................................................................................................................16
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List of Abbreviations
AE: Adverse event
AEF: Atrio-esophageal fistula
AF: Atrial Fibrillation
EGD: Oesophagogastroduodenoscopy
EMR: Electronic Medical Record
LET:  luminal esophageal temperature
RF:  Radiofrequency
SAE: Serious adverse event
SOC: Standard of care
UP:  Unanticipated Problem
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Study Summary
Title
Utility of Esophageal Temperature Management for the Prevention of 
Thermal Injury During Atrial Fibrillation Ablation
Short Title
Esophageal Temperature Management During Cryo AF Ablation
NU IRB Number
STU00209610 
Phase
Pilot Study 
Methodology
Randomized, blinded, single center pilot study  
Study Duration
12 months
Study Center
Northwestern University
Objectives
Primary:

To determine the occurrence rate of esophageal thermal injury 
between groups

To determine the severity and size of esophageal injury between 
groups
Secondary:

Determine the occurrence and location of acute PV reconnection

Determine freedom from AF at 3 months, 6 months, and 12 months
Number of Participants
40
Length of Participation
2-3 days intervention phase; 3 month follow up, 1 year data collection
Inclusion Criteria
1.
Patients above the age of 18 years old.
2.
Patients with the diagnosis of atrial fibrillation undergoing clinically 
indicated de-novo AF ablation procedure.
3.
Patients must be able to understand and critically review the informed 
consent form.
Exclusion Criteria
1.
Patients whom are unable to provide informed consent.
2.
Patients with contraindication to EGD.
3.
History of prior AF ablation procedures.
4.
Significant co-morbidities that preclude standard ablation procedure
5.
Patients with <40 kg of body mass
Investigational Device
Attune Medical Esophageal Heat Transfer Device- EnsoETM 
Used during standard of care AF ablation  
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Duration of 
administration 
During AF ablation (3-6 hours)
Reference therapy
EnsoETM will replace standard of care temperature probe
Statistical 
Methodology
Based on prior studies, esophageal injury following ablation is anticipated to 
be approximately 17% in the control group. A total of 20 patients for each 
group will be required to yield the necessary pilot data to make an 
appropriate conclusion regarding the effect of esophageal thermal cooling on 
prevention of esophageal thermal injury. 
Safety Evaluations 
All patients will undergo oesophagogastroduodenoscopy (EGD) 1-2 days 
following the ablation procedure.  
Data and Safety 
Monitoring Plan 
The PI and research team will be responsible for data and safety monitoring.
This study will be conducted in full accordance all applicable Northwestern University Research Policies and 
Procedures and all applicable Federal and state laws and regulations.
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1.0 Background and Study Rationale
1.1
Introduction
Cathter ablation of atrial fibrillation (AF) has become a common ablation procedure performed worldwide. The 
cornerstone of this procedure is pulmonary vein isolation (PVI). PVI can be achieved by multiple methods, the two 
most common being radiofrequency (RF) and cryoablation.  Energy delivery may extend beyond the atrial 
myocardium and result in damage to adjacent structures, including the esophagus. Atrio-esophageal fistula (AEF) 
is a rare, but a well-recognized complication of percutaneous AF ablation with an estimated incidence of 0.02–
0.11%1. Although the pathophysiology is not entirely understood, it is clear that thermal injury to the esophagus 
during ablation of the posterior left atrial wall plays a crucial role in triggering a cascade of events that eventually 
results in the development of AEF. Common clinical strategies to prevent esophageal injury include delivery of lower 
ablation energy along the posterior left atrium as well as the use of a luminal esophageal temperature (LET) probe 
aimed to alert and guide energy delivery. Nonetheless, esophageal injury is still common, and AEF continues to be 
reported despite adherence to these guidelines. 
1.2
Background and Relevant Literature 
Due to the low occurrence rate of AEF, prior studies aimed to develop strategies to prevent it have used the 
occurrence of esophageal injury as assessed with endoscopy as a surrogate endpoint. The occurrence rate of 
esophageal injury has varied depending on the reporting center, timing of endoscopy, and the ablation technique 
utilized. Esophageal ulceration is likely the initial injury that leads to AEF formation and is probably present within 
hours to days of the ablation procedure. Deneke et al. have assessed the outcomes of >800 patients who underwent 
first-time catheter ablation of AF followed by EGD within 4 days of the procedure. They found that 82% of patients 
had EGD without esophageal lesions and no subsequent esophageal events. Of the patients with esophageal 
abnormalities, two-thirds had erythema with no further complications. The 5 documented esophageal perforations 
occurred in patients with esophageal ulceration (ratio of esophageal perforation to ulcer, 1:10)2. Another study 
showed evidence of esophageal thermal injury in 9/20 (45%) on EGD the day after the ablation procedure3. 
1.3
Name and Description of the Study Device 
The Attune Medical Esophageal Heat Transfer Device (EnsoETM) is an FDA approved device.  The EnsoETM is a 
non-sterile multi-lumen silicone tube placed in the esophagus for the purpose of cooling or warming a patient while 
simultaneously allowing gastric decompression and drainage. Modulation and control of the patient’s temperature 
is achieved by connecting the EnsoETM to an external heat exchanger (Blanketrol III, Cincinnati SubZero). Two 
lumens connect to the external heat exchanger, while a third central lumen provides stomach access for connection 
to a fluid collection device with low intermittent suction for gastric decompression. Distilled water circulates within 
the EnsoETM just like a water blanket. The EnsoETM is made of standard medical-grade silicone. The versatile 
device can be placed by most providers in a procedure or operating room, emergency room, or intensive care unit. 
Providers placing devices will be appropriately trained.  The EnsoETM is a single-use, disposable, non-implantable 
device with an intended duration of use of 72 hours or less. For this study, the device will be used during cardiac 
ablation procedures for the intended indication of patient temperature management using approved 
settings/parameters as detailed in the product instructions for use document. 
1.3.1
Nonclinical Data
While, there is no published pre-clinical animal data with this device, an in-vivo animal study using a different 
esophageal balloon device has been performed. Using an animal model, Arruda, et al. demonstrated that the use 
of a compliant balloon device that circulates cold fluid between 5-10C can prevent collateral thermal injury to the 
esophagus4 during RF ablation. In this study, the authors demonstrate that they were able to safely perform 
esophageal cooling to prevent esophageal thermal injury without adversely affecting the surrounding structures or 
the biophysical parameters of the radiofrequency ablation lesions4.   In this study, cryoenergy will be used to perform 
PVI.  The EnsoETM device will be used to circulate warm water (42C) in order to try and prevent thermal lesion 
formation within the esophagus.
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1.3.2
Clinical Data to Date
One clinical observational study has indicated that esophageal cooling can reduce thermal injury during RF AF 
ablation, but this strategy is not routinely used in clinical practice and has not been evaluated for cryoablation PVI. 
Ahmed, et al. reported in an observational study that included 67 patients that the incidence of thermal injury during 
cryoablation for AF is 17%5. Based on these and prior studies, it is our hypothesis that the use of the EnsoETM 
device may reduce the occurrence and/or severity of esophageal thermal injury as it is a compliant balloon 
technology that can reach a warming temperature of 42C. In addition, it is FDA cleared and has been used safely 
in thousands of patients for temperature control making it the ideal device to use for this study.
2
Study Objectives
The purpose of the proposed pilot study is to determine if esophageal warming using the Attune Medical Esophageal 
Heat Transfer Device (EnsoETM) limits the frequency or severity of thermal injury during cryoballoon ablation of 
atrial fibrillation. 
2.1
Primary Objectives
1.
To determine the occurrence rate of esophageal thermal injury between groups
2.
To determine the severity and size of esophageal injury between groups
2.2
Secondary Objectives 
1.
Determine the occurrence and location of any acute PV reconnection between groups
2.
Determine freedom from AF at 3 months, 6 months, and 12 months
3
Investigational Plan 
3.1
General Design
This is a small-scale, pilot study to evaluate if esophageal warming using the Attune Medical Esophageal Heat 
Transfer Device (EnsoETM) limits the frequency or severity of thermal injury during catheter ablation of atrial 
fibrillation.  This prospective, randomized study will include 40 patients with symptomatic AF undergoing index PVI 
under general anesthesia at the Northwestern Memorial Hospital. Patients will be randomized in a 1:1 fashion with 20 
patients (Group A) randomized to undergo the ablation procedure with esophageal warming and the other 20 patients 
(Group B) will serve as the control group and will not have the EnsoETM device used. Patients randomized to Group A 
will have the EnsoETM device placed in the electrophysiology laboratory following intubation and prior to the ablation 
procedure. AF ablation will be carried out in a standard fashion.  All patients will undergo esophagogastroduodenoscopy 
(EGD) 1-2 days following the ablation procedure.  
3.1.1
Screening Phase
Subjects will be recruited from those selected to undergo cryoablation PVI under general anesthesia.  Patients will 
first be pre-screened using the procedure schedule to identify those that are undergoing an initial AF ablation 
procedure and therefore may be potentially eligible for enrollment. Patients who have met guideline 
recommendations for first-time AF ablation procedure will be approached by an EP physician (co-investigators) or 
a member of the research team prior to the AF ablation procedure.  All potentially eligible patients will first have 
signed an informed consent for the clinical procedure by the appropriate clinical staff.  We will follow applicable 
University regulations and Illinois law pertaining to consent process and obtaining signatures. Written informed 
consent for the research study (use of EnsoETM + EGDs) will be obtained the morning of the clinical procedure 
prior to any research procedures taking place.
3.1.2
Study Intervention Phase 
Participants who have signed the research study consent form will be randomized in a 1:1 fashion to the study 
device (EnsoETM) or to standard of care (standard temperature probe monitoring). Insertion of the study device will 
be in place of the standard temperature probe and will not add any additional time or change the protocol of the 
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standard AF ablation procedure.  The device will be used as for warming. Temperature measures will be collected 
for both the device and standard of care (SOC) arms during the clinical ablation procedure.  
Ablation Procedure (Day 0)
Cryoballoon ablation for PVI under general anesthesia will be performed via the standard technique. For those patients 
randomized to group A, the EnsoETM will be placed immediately following induction of general anesthesia.
Endoscopic Evaluation (Day 1)
All patients will undergo EGD the day after the ablation procedure. These will be performed via a standard technique.  
Studies will be interpreted for research purposes by an experienced gastroenterologist who is blinded to the patient’s 
study group. Esophageal injury will be attributed to ablation if located on the anterior wall of the mid-esophagus (20 to 
30 cm from the incisors). EGD findings of thermal injury will be classified into four injury grades: (1) erythema – mild 
injury; (2) superficial ulceration – moderate injury; (3) deep ulceration – significant injury; and (4) fistula/perforation. 
Clinical interpretation of the EGD study will still be performed and reported in Epic by a Northwestern gastroenterologist 
according to standard clinical guidelines. 
3.1.3
Post-Ablation Follow Up Visit
Follow up data will be collected at approximately 2-3 months following the ablation procedure.  This is a standard 
of care follow up visits that typically occurs following an atrial fibrillation ablation procedure.  The standard of care 
procedures that will be done at these visits include:

Physical Exam

Interim History and concomitant medication use

Vital signs
In addition to the standard of care procedures, the research team will also collect the following:

Adverse event information 

Atrial fibrillation recurrence
If a participant does not attend their routine 3 month clinical follow up, the research staff will attempt to contact the 
participant by phone to review their interim history, medication use and collect adverse event and atrial fibrillation 
recurrence information. 
3.1.4
Follow Up Data Collection Phase (chart review)
The standard of care follow-up visits that typically occur following an atrial fibrillation ablation procedure will be 
documented by the clinical care team in the participant’s electronic medical record (EMR) and will be reviewed by 
research staff for follow up data collection.  This typically occurs at approximately 2-3 months, 6 months and 12 
months post ablation.  The research team will collect the following data, if available:

Physical Exam findings

Interim History and concomitant medication use

Vital signs

Monitoring to assess for atrial fibrillation recurrence
If a participant does not attend any of their 12 month clinic visit, research staff will attempt to contact the participant 
by phone to discuss medical history and recurrence of atrial fibrillation. 
3.1.5
Randomization
The randomization scheduled will be generated by a statistician in the Clinical Trials Unit (CTU). Participants will 
be assigned the next sequential randomization number from the randomization schedule. Subjects will be 
randomized (1:1) to either study device (Group A – Esophageal Warming) or standard of care (Group B – Control). 
Patients will undergo randomization after being enrolled into the study and prior to the start of the clinically indicated 
AF ablation procedure.  Randomization numbers will not be re-used or re-assigned. 
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3.2
 Study Endpoints 
The purpose of the proposed pilot study is to determine if esophageal warming using the Attune Medical Esophageal 
Heat Transfer Device (EnsoETM) limits the frequency or severity of thermal injury during catheter ablation of atrial 
fibrillation. 
3.2.1
Primary Study Endpoints
The primary endpoints of this study will be:
1.
Occurrence rate of esophageal thermal injury between groups
2.
Severity (Grade 1-4) and number of esophageal thermal injuries 
3.2.2
Secondary Study Endpoints
1.
Occurrence and location of any acute PV reconnection
2.
Freedom from AF at 3 months, 6 months, and 12 months
3.2.3
Primary Safety Endpoints 
All patients will undergo EGD the day after AF ablation to evaluate the primary endpoint of esophageal thermal 
injury.  We will also collect adverse events for all participants 3 months following the ablation procedure.
4
Study Population and Duration of Participation 
All patients will have met guideline recommendations for the AF ablation procedure and will have signed an informed 
consent for the clinical procedure.  
4.1
Inclusion Criteria
1.
Patients above the age of 18 years old.
2.
Patients with the diagnosis of atrial fibrillation undergoing clinically indicated de-novo AF ablation 
procedure.
3.
Patients must be able to understand and critically review the informed consent form.
4.2
Exclusion Criteria
1.
Patients with contraindication to EGD.
2.
History of prior AF ablation procedures.
3.
Significant co-morbidities that preclude standard ablation procedure.
4.
Patient is ineligible for EnsoETM placement due to:
o
Known esophageal deformity or evidence of esophageal trauma (for example history of 
esophagectomy, previous swallowing disorders, achalasia).
o
Known ingestion of acidic or caustic poisons within the prior 24 hours.
o
Patients with <40 kg of body mass.
4.3
Subject Recruitment 
Subjects will be recruited for the study from investigator or sub-investigator clinical practices who have a diagnosis 
of atrial fibrillation and will undergo a clinically indicated de-novo cryo AF ablation procedure at Northwestern 
Memorial Hospital.  
4.4
Duration of Study Participation
Participants will be involved for approximately 13 months including screening and follow-up.  After consent, their 
active participation in the intervention phase will last 24-48 hours to complete the ablation procedure and EGD 
testing.  The follow up for safety evaluation will occur approximately 2-3 months post-ablation during a routine 
clinical follow up visit.  Additional data will be collected via chart review through 1-year post-ablation from routine 
clinical follow up care post ablation which occurs at approximately 6 and 12 months.  
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4.5
Total Number of Subjects and Sites 
Recruitment will end when approximately 40 participants are randomized. It is expected that approximately 50 
subjects will be consented in order to produce 40 randomized & evaluable subjects. 
5
Study Intervention 
5.1
Device Description
The EnsoETM is a non-sterile multi-lumen silicone tube placed in the esophagus for the purpose of cooling or 
warming a patient while simultaneously allowing gastric decompression and drainage. Modulation and control of 
the patient’s temperature is achieved by connecting the EnsoETM to an external heat exchanger. Two lumens 
connect to the external heat exchanger, while a third central lumen provides stomach access for connection to a 
fluid collection device with low intermittent suction for gastric decompression. The EnsoETM is made of standard 
medical-grade silicone. It is a single-use, disposable, non-implantable device with an intended duration of use of 72 
hours or less. Distilled water circulates within the EnsoETM just like a water blanket.
The EnsoETM is a 510K FDA approved device.  For this study, the device will be used during cardiac ablation for 
the intended indication of patient temperature management using approved settings/parameters as detailed in the 
product instructions for use. 
5.2
Intervention Regimen
Patients who are randomized to the EnsoETM device will have the device placed in the electrophysiology laboratory 
following intubation and prior to the ablation procedure. The device will remain in place until the ablation procedure is 
completed. The device will be set to 42ºC during all aspects of the procedure.
5.3
Storage
The EnsoETM device should be stored in a dry and secure location in the EP laboratory or clinical research 
department.  This device is for single use only.  Reuse may expose patient to infection risks.  Investigators should 
not use the device if the packaging is compromised.  
5.4
Preparation and Packaging & Supply
The EnsoETM device will be packaged and supplied by Attune Medical.  
5.5
Blinding
Due to the nature of this study, the physicians will not be blinded to the randomization assignment, however 
participants will be blinded prior to the procedure.  Once a subject is randomized, the research team will receive the 
randomization assignment (EnsoETM or SOC) and proceed with the procedures per the assignment. In addition, 
the gastroenterologist interpreting the EGD study for the primary endpoint assessment will be blinded to the 
participants’ randomization. Participants will be informed of assignment (EnsoETM or SOC) at the time of their first 
post-ablation follow-up visit.
5.6
Device Accountability   
Device accountability logs will be kept on file, will be completed on a regular basis, and will include product number, 
date of use, participant ID code, device damaged/destroyed and date of damage/destruction (including return date 
to Attune). 
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6
Schedule of Study Visits, Procedures, and Data Extraction
Study Phase
Randomization/
Intervention Phase 
Follow up 
Visit Number
1
2
Chart Review*
Study Days
Day 0
Day 1
(2-3, 6, 12 mo)
Research & Clinical Procedures
Informed Consent
X
Review Inclusion/Exclusion Criteria
X
Randomization 
X
Ablation procedure (with temperature 
monitoring or EnsoETM device)
X
Overnight monitoring post ablation
X
EGD (Esophagogastroduodenoscopy) 
X
Discharge (1-day post ablation)
X
Adverse Event / Unanticipated Problems 
Assessment
X
X
X**
Data collection
Demographics
X
Medical History/Interim History*
X
X
X
Physical Examination*
X
X
X
NYHA
X
Vital Signs: BP, HR, RR*
X
X
X
Height and Weight
X
Pregnancy Test
X
Clinical Laboratory Evaluation
X
X
Clinical Imaging
X
Prior/Concomitant Medications
X
X
* Interim medical history, physical exam, and vitals will be collected via chart review from routine clinical care 
follow up post-ablation visits that occur at approximately 2-3, 6 and 12 months. ** AE assessed only at the 
2-3 month follow-up visit.
6.1
Pre-Screening
Patients will be pre-screened by the study team via EMR using data/testing collected for clinical purposes prior to 
the Randomization visit to determine potential eligibility. Patients identified as potentially eligible will be approached 
for participation in the research study.  
6.2
Study Visits & Data Collection
6.2.1
Visit 1/Day 0 (Screening, Enrollment, Randomization, and Ablation) 
Study personnel will assess each subject against each inclusion and each exclusion criterion and the Investigator 
will determine the subject’s eligibility for study participation.  Appropriately delegated study staff will review the 
consent form with subjects. The principal investigator or appropriately delegated members of the research team 
will also discuss the underlying rationale for the study, the procedures to be followed, the potential benefits and 
risks, and other issues mandated by the consent process. Delegated study physicians, will discuss the 
device/risks/benefits and obtain documented consent.   Before or after the discussion of risks and benefits of the 
experimental product by the study physician, a study nurse or clinical coordinator may consent the research 
subject with respect to all other aspects of the research. The participant will be given the consent form for review 
and will be given the time to ask questions and have them answered.  The participant will be asked if they would 
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like to participate, and if so, this will be documented using the study ICF.  Determining the eligibility for each 
participant will require information generated during the course of routine clinical care as dictated by their 
attending physicians. Selected testing data will be collected in order to characterize the type, cause and severity 
of the patient’s AF and the treatments received prior to enrollment. The data will include information from the 
evaluations listed below.
Once eligibility is confirmed, the research staff will o obtain the randomization assignment from the CTU statistician.  
The following procedures will be performed during Visit 1:
Research and Clinical Procedures:

Clinical consent for ablation procedure

Study Informed Consent 

Documentation of Inclusion/Exclusion criteria review

Randomization

Ablation procedure (with standard temperature monitoring or with EnsoETM)

Overnight post-op monitoring 

Adverse Event/Unanticipated Problem assessment and recording
Data collection from Clinical procedures:

Collect Demographics (including sex/gender, race, ethnicity, and age via date of birth)

Medical Record Review (including any history of disease, social history, physical exam findings and 
progress notes) 

Review of Concurrent Medications

Physical Exam 

Vital Signs: blood pressure, heart rate, respiration rate, height and weight

Routine Clinical Labs/Phlebotomy: such as a complete blood count (CBC) and chemistry profiles

Pregnancy test for women of childbearing potential

New York Heart Association Assessment – classification of heart failure based on symptoms and functional 
limitations
6.2.2
Visit 2 (Post-op day 1)
As part of routine post-op monitoring, participants will stay overnight in the hospital for monitoring.  They may be 
discharged the following day or as determined by their clinical status.  Prior to discharge, we will conduct Visit 2 
assessment.  
The following procedures will be collected at Visit 2:

Interim medical history review

Physical Exam

Vital Signs

Research EGD (Esophagogastroduodenoscopy) 

Adverse Event/Unanticipated Problem assessment and recording
6.2.3
Visit 3 (Post ablation Month 3)
Participants will be scheduled for a routine follow up visit post-ablation by the clinical staff at approximately 3 months 
after having had the ablation procedure.  
The following procedures will be collected at Visit 3:

Interim medical history review /concomitant medications

Physical Exam & Vital Signs

Adverse Event/Unanticipated Problem assessment and recording
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Participants that do not return for their clinical follow up will be contacted by the research staff at approximately 2 
months to collect interim history, medication use, and adverse event information. 
6.2.4
Follow up data collection (Post ablation Months 6,12)
Participants will be scheduled for standard of care follow-up monitoring by the clinical staff at approximately 6 
months and 12 months after having had the ablation procedure.  
The following data will be collected from the EMR if available:

Interim medical history/concomitant medications

Monitoring for AF recurrence
For those patients that do not return for the Month 3 and Month 12 follow-up clinic visits, the research team will 
contact participants at 4 and 13 months to review medical history and recurrence of atrial fibrillation .
6.3
Rescue Therapy 
The EnsoETM device will be removed and replaced if at any time there is evidence of a potential device malfunction, 
such as the inability to adequately reach target warming temperature. The device can be easily removed and 
replaced during the ablation procedure if needed. Should evidence of continued malfunction occur after replacement 
of the study device, the EnsoETM will be removed and replaced with the standard temperature probe allowing the 
patient to undergo the standard ablation procedure. 
6.4
Unscheduled Visits
The research team will assess for the occurrence of any adverse event(s) / unanticipated problem (s) should a 
patient present for any unscheduled visit to Northwestern Cardiology or GI clinical practice up through 90 days 
following the ablation procedure. 
6.5
Subject Withdrawal 
Subjects may withdraw from the study at any time without impact to their care.  They may also be discontinued from 
the study at the discretion of the Investigator for lack of adherence to study procedures or visit schedules, AEs, or 
should it become clinically necessary to deviate from the study protocol during the course of the ablation procedure. 
The Investigator may also withdraw subjects who violate the study plan, or to protect the subject for reasons of 
safety or for administrative reasons.  It will be documented whether or not each subject completes the clinical study. 
We will attempt to have one final visit or contact to follow up regarding adverse events for participants who withdraw 
prior to the 3 Month follow up visit. 
6.5.1
Data Collection and Follow-up for Withdrawn Subjects
We will attempt to have one final visit or contact to follow up regarding adverse events for participants who withdraw 
prior to the 3 Month follow up visit. During this contact they will be asked for permission to have the study team look 
into their survival status via their electronic medical records and publicly available means.  
 
7
Statistical Plan
Primary Endpoint
The primary endpoint of this study will be the occurrence rate of esophageal thermal injury, the severity (Grade 1-
4) of thermal injuries, and number of distinct injuries present. This will be assessed by blinded gastroenterologist 
using images captured during the EGD procedure.  
7.1
Secondary Endpoints 
Secondary endpoints include:
1.
Occurrence and location of any acute PV reconnection
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2.
Freedom from AF at 3 months, 6 months, and 12 months
7.2
Sample Size and Power Determination
Based on prior studies, esophageal injury following ablation is anticipated to be approximately 17% in the control 
group. However, as we do not know the occurrence rate of the primary outcome of esophageal injury using the 
Northwestern ablation technique that would represent the control group nor in the device arm we are unable to 
accurately perform a power calculation for this pilot study. We believe that a total of 20 patients for each group will 
be required to yield the necessary pilot data to make an appropriate conclusion regarding the potential utility of 
esophageal thermal warming using this device on the reduction of esophageal thermal injury. It is also anticipated 
that data from this pilot study can be used for planning future larger studies.
7.3
Statistical Methods
We will utilize a calculated esophageal lesion score to account for both lesion severity and the number of distinct 
lesions identified per patient for comparison between patient groups. The score will be a four-digit number WXYZ 
where each digit represents the number of lesions at each severity level per patient defined as: Z: Grade 1; Y: 
Grade 2; X Grade 3; W: Grade 4. This will be inputted into the following formula in order to calculate the thermal 
injury score for each patient: Score = 1000*W + 100*X + 10*Y + Z.  
7.3.1
Baseline Data
Baseline and demographic characteristics will be summarized by standard descriptive statistics (including mean 
and standard deviation for continuous variables such as age and standard percentages for categorical variables 
such as gender).
7.3.2
Efficacy Analysis 
This is a pilot study to determine the potential role of the EnsoETM device for the prevention and/or reduction of 
esophageal thermal injury during atrial fibrillation ablation procedures. This analysis will be performed using the 
calculated esophageal lesions score as described above based on the primary outcome data of thermal injury 
occurrence rate, severity (Grade 1-4) of injuries, and number of distinct injuries present between study groups. 
7.3.3
Interim Safety Analysis 
All subjects entered into the study and randomized at the baseline visit will have detailed information collected on 
adverse events for the overall study safety analysis. An interim safety analysis will be performed after the first 10 
subjects are enrolled in the trial. At this time the safety and tolerability of the study device and research EGD 
procedure will be assessed and if, deemed safe and appropriate, enrollment will continue up to 40 subjects. 
7.4
Subject Population(s) for Analysis
All patients enrolled, randomized to a study arm, and complete the initial phase of the study (ablation procedure 
and EGD) will be included for analysis. 
8
Safety and Adverse Events
8.1
Definitions
8.1.1
Unanticipated Adverse Device Effect
An Unanticipated Device Effect is 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.
Serious injury:
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Any injury or illness that is any one of the following: 

life-threatening

results in permanent impairment of a body function or permanent damage to body structure

necessitates medical or surgical intervention to preclude permanent impairment of a body function or 
permanent damage to a body structure
8.1.2
Adverse Event
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity during the 
course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  Abnormal results of 
diagnostic procedures are considered to be adverse events if the abnormality:

results in study withdrawal

is associated with a serious adverse event

is associated with clinical signs or symptoms

leads to additional treatment or to further diagnostic tests

is considered by the investigator to be of clinical significance
8.1.3
Serious Adverse Event
Serious Adverse Event
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is: 

fatal

life-threatening

requires or prolongs hospital stay

results in persistent or significant disability or incapacity

a congenital anomaly or birth defect

an important medical event
Important medical events are those that may not be immediately life threatening, but are clearly of major clinical 
significance.   They may jeopardize the subject, and may require intervention to prevent one of the other serious 
outcomes noted above.  For example, drug overdose or abuse, a seizure that did not result in in-patient 
hospitalization, or intensive treatment of bronchospasm in an emergency department would typically be considered 
serious. 
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious adverse 
events. 
8.1.4
Unanticipated Problems(UP) Involving Risk to Subjects or Others
Any incident, experience, or outcome that meets all of the following criteria: 

Unexpected in nature, severity, or frequency (i.e. not described in study-related documents such as the IRB-
approved protocol or consent form, the investigators brochure, etc)

Related or possibly related to participation in the research (i.e. 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)

Suggests that the research places subjects or others at greater risk of harm (including physical, 
psychological, economic, or social harm).
8.1.5
Preexisting Condition
A preexisting condition is one that is present at the start of the study.  A preexisting condition should be recorded 
as an adverse event if the frequency, intensity, or the character of the condition worsens during the study period.
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8.1.6
General Physical Examination Findings
At screening, any clinically significant abnormality should be recorded as a preexisting condition.  At the end of the 
study, any new clinically significant findings/abnormalities that meet the definition of an adverse event must also be 
recorded and documented as an adverse event. 
8.1.7
Post-study Adverse Event
All unresolved adverse events considered probably or definitely related should be followed by the investigator until 
the events are resolved, the subject is lost to follow-up, or the adverse event is otherwise explained.  At the last 
scheduled visit, the investigator should instruct each subject to report any subsequent event(s) that the subject, or 
the subject’s personal physician, believes might reasonably be related to participation in this study.  
8.1.8
Hospitalization, Prolonged Hospitalization or Surgery
Any adverse event that results in hospitalization or prolonged hospitalization should be documented and reported 
as a serious adverse event unless specifically instructed otherwise in this protocol.  Any condition responsible for 
additional surgery should be documented as an adverse event if the condition meets the criteria for and adverse 
event. 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an adverse event in 
the following circumstances:

Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for a preexisting 
condition.  Surgery should not be reported as an outcome of an adverse event if the purpose of the surgery 
was elective or diagnostic and the outcome was uneventful.

Hospitalization or prolonged hospitalization required to allow efficacy measurement for the study.

Hospitalization or prolonged hospitalization for therapy of the target disease of the study, unless it is a 
worsening or increase in frequency of hospital admissions as judged by the clinical investigator.
8.2
Recording of Adverse Events
At each contact with the subject, the investigator will seek information on adverse events by specific questioning 
and, as appropriate, by examination.  Information on all adverse events will be recorded immediately in the source 
document, and also in the appropriate adverse event case report form (CRF).  All clearly related signs, symptoms, 
and clinically significant abnormal diagnostic procedures results should be recorded in the source document, though 
should be grouped under one diagnosis.
All adverse events occurring during the study period (consent through Visit 3, 3 month follow up) will be recorded.  
The clinical course of each event will be followed until resolution, stabilization, or until it has been determined that 
the study intervention or participation is not the cause.  Serious adverse events that are still ongoing at the end of 
the study period will be followed up to determine the final outcome.  Any serious adverse event that occurs after the 
study period and is considered to be possibly related to the study intervention or study participation will be recorded 
and reported immediately.
8.3
Classification of Adverse Events
Severity

Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention is not 
indicated.

Grade 2: moderate; minimal, local, or noninvasive intervention is indicated; limiting to age-appropriate 
instrumental activities of daily living (ADL; instrumental ADL refers to preparing meals, shopping for 
groceries or clothes, using the telephone, managing money, etc.).

Grade 3: severe or medically significant but not immediately life threatening; hospitalization or prolongation 
of hospitalization is indicated; disabling; limiting to self-care ADL (self-care ADL refers to bathing, dressing 
and undressing, feeding self, using the toilet, taking medications, and not bedridden).

Grade 4: life-threatening consequences; urgent intervention is indicated.
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
Grade 5: death due to an AE.
Relatedness
1) Definite: the AE is clearly related to the research procedures
2) Probably: the AE is likely related to the research procedures
3) Possible: the AE may be related to the research procedures
4) Unlikely: the AE is doubtfully related to the research procedures
5) Unrelated: the AE is clearly not related to the research procedures
Expectedness
AEs must be assessed as to whether they were expected to occur or were unexpected, meaning not anticipated 
based on current knowledge found in the protocol, investigator brochure, product insert, or label.
Expected: an AE known to be associated with the intervention or condition under study.
OHRP defines an unexpected AE as any AE occurring in one or more subjects participating in a research protocol, 
the nature, severity, or frequency of which is not consistent with either:
1)
the known or foreseeable risk of AEs associated with the procedures involved in the research that are 
described in a) the protocol-related documents, such as the IRB-approved research protocol, any 
applicable investigator brochure, and the current IRB-approved informed consent document, and b) other 
relevant sources of information, such as product labeling and package inserts; or
2) the expected natural progression of any underlying disease, disorder, or condition of the subject(s) 
experiencing the AE and the subject’s predisposing risk factor profile for the AE.
 
8.4
Adverse Event Reporting Period
For this study period during which adverse events must be reported is defined as the period from the initiation of 
any study procedures (consent) to the end of the study follow-up (Visit3).  Adverse events that do not require 
expedited reporting will be reported in summary to the IRB at continuing review.
8.5
Expedited Reporting of Events
Any study-related unanticipated problem posing risk to subjects or others, and any type of serious adverse event 
or unanticipated device reaction, will be reported to the IRB and funding sponsor within 24 hours of knowledge of 
the event.  Investigators will use the appropriate SAE/UP CRF to record events and a line item will also be added 
to the AE log CRF.
The minimum necessary information to be provided at the time of the initial expedited event report includes:

Study identifier

Study Center

Subject number

A description of the event

Date of onset

Current status

Whether study intervention was discontinued

The reason why the event is classified as serious

Investigator 
assessment 
of 
the 
association 
between the event and study intervention
8.5.1
Follow-up report
If an SAE, UP or Unanticipated Adverse Device Effect has not resolved at the time of the initial report and new 
information arises that changes the investigator’s assessment of the event, a follow-up report including all relevant 
new or reassessed information (e.g., concomitant medication, medical history) should be submitted to the IRB. The 
investigator is responsible for ensuring that all events are followed until either resolved or stable. 
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8.5.2
Sponsor reporting: Notifying the Funding Sponsor 
Electronic notification of any adverse events related to the use of the EnsoETM study device will be sent to the 
funding sponsor as determined by the principal investigator and study team. 
8.6
Unblinding Procedures
The study team will not be blinded to the randomization assignment.  The study team will be instructed to maintain 
blinding for participants unless a participant has a clinical need to know their randomization assignment.  The 
decision to unblind will be at the discretion of the study PIs and only if unblinding would change clinical care.  
Unblinding for safety reasons will be recorded in study records and it will be reported to the IRB and the funding 
sponsor at the time of continuing review. 
8.7
Data and Safety Monitoring
It is the responsibility of the Principal Investigator to oversee the safety of the study. The Principal Investigator and 
designated members of the study team will be responsible for monitoring subject safety and applicable reporting to 
the IRB and study sponsor.  This safety monitoring will include careful assessment of eligibility and detailed 
assessment and appropriate reporting of adverse events as noted above. Grading of EGDs will be done by a single 
physician contracted to perform the reads.  Data collected on the study will be reviewed after 10 people are enrolled 
in the study.  
9
Study Administration, Data Handling and Record Keeping
9.1
Confidentiality
Information about study subjects will be kept confidential and managed according to the requirements of the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA).  Those regulations require a signed subject 
authorization informing the subject of the following: 

What protected health information (PHI) will be collected from subjects in this study

Who will have access to that information and why

Who will use or disclose that information

The rights of a research subject to revoke their authorization for use of their PHI. 
In the event a subject revokes authorization to collect or use PHI, the investigator, by regulation, retains the ability 
to use all information collected prior to the revocation of subject authorization.  For subjects that have revoked 
authorization to collect or use PHI, attempts should be made to obtain permission to collect at least vital status (i.e. 
that the subject is alive) at the end of their scheduled study period.
9.2
Data Collection and Management 
Data will be collected by trained research staff using source documents and CRFs.  Source and CRFs will be 
entered into a RedCap data management system (DMS).  Participants will be assigned a Participant ID “PID” for 
use on CRF data collection in for entry into the DMS to protect and ensure confidentiality. 
Source data is all information, original records of clinical findings, observations, or other activities in a clinical trial 
necessary for the reconstruction and evaluation of the trial.  Source data are contained in source documents.  
Examples of these original documents, and data records include: hospital records, clinical and office charts, 
laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded 
data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, 
microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the 
pharmacy, at the laboratories, and at medico-technical departments involved in the clinical trial.
The study case report form (CRF) is the primary data collection instrument for the study.  All data requested on the 
CRF must be recorded.  All missing data must be explained.  If a space on the CRF is left blank because the 
procedure was not done or the question was not asked, write “N/D”.  If the item is not applicable to the individual 
case, write “N/A”.  All entries should be printed legibly in black ink.  If any entry error has been made, to correct 
such an error, draw a single straight line through the incorrect entry and enter the correct data above it.  All such 
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changes must be initialed and dated.  DO NOT ERASE OR WHITE OUT ERRORS.  For clarification of illegible or 
uncertain entries, print the clarification above the item, then initial and date it. 
The study data will be stored indefinitely.  A de-identified data set may be shared with the funding sponsor.  
9.3
Records Retention 
Study records, including administrative and participant related source and CRFs, will be retained for 3 years after 
the completion of the research (often marked by a final progress report). 
10 Study Monitoring, Auditing, and Inspecting
10.1
Study Monitoring Plan
The investigator and research team will allocate adequate time for monitoring activities, as necessary.  The 
Investigator will also ensure that the monitor or other compliance or quality assurance reviewer is given access to 
all the above noted study-related documents and study related facilities (e.g. clinical EP laboratories), and has 
adequate space to conduct the monitoring visit.
10.2
Auditing and Inspecting
The investigator will permit study-related monitoring, audits, and inspections by the IRB, government regulatory 
bodies, and University compliance and quality assurance groups of all study related documents (e.g. source 
documents, regulatory documents, data collection instruments, study data etc.).  The investigator will ensure the 
capability for inspections of applicable study-related facilities.
Participation as an investigator in this study implies acceptance of potential inspection by government regulatory 
authorities and applicable University compliance and quality assurance offices.
11 Ethical Considerations
This study is to be conducted in accordance with applicable US government regulations and international standards 
of Good Clinical Practice, and applicable institutional research policies and procedures.
This protocol and any amendments will be submitted to a properly constituted Institutional Review Board (IRB), in 
agreement with local legal prescriptions, for formal approval of the study conduct.  The decision of the IRB 
concerning the conduct of the study will be made in writing to the investigator and a copy of this decision will be 
provided to the funding sponsor before commencement of this study if required. The formal consent of a subject, 
using the IRB-approved consent form, must be obtained before that subject undergoes any study procedure.  The 
consent form must be signed by the subject or legally acceptable surrogate, and the appropriately delegated 
research staff obtaining the consent.
11.1
Risks
Risks of the ablation procedure will be explained using the clinical procedure consent.
Additional risks of the study procedures are described below:
EnsoETM device risks: Placement of the EnsoETM device, similar to any device in the esophagus, can result in or 
exacerbate esophageal tissue damage, particularly in patients with known esophageal deformity or evidence of 
esophageal trauma. We believe these risks are similar to those whom receive the standard of care temperature 
monitor probes inserted into the esophagus during routine clinical procedures. 
EGD procedure risks:  Diagnostic upper endoscopy procedures are considered very safe and rarely can result in 
complications including bleeding, infection, and/or perforation. Large studies have reported the occurrence of any 
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adverse event anywhere from 1 in 200 to 1 in 10,000 patients with major complications or death extraordinarily 
rare6. 
Loss of Confidentiality Risks:  there is the potential for loss of confidentiality during data collection. 
11.2
Benefits
There are no known direct benefits to the participants in this study.  There may be a benefit to warming the 
esophagus to reduce or prevent damage during the ablation procedure.  The knowledge gained by participation in 
this study may benefit society as a whole in the future and potentially lead to additional studies. 
11.3
Risk Benefit Assessment
The risks of participating in the study are outweighed by the potential benefits of participating in the study. 
11.4
Informed Consent Process / HIPAA Authorization 
Participants will be provided an IRB approved consent form describing this study and providing sufficient information 
for subjects to make an informed decision about their participation in this study. A verbal review of the consent form 
will take place with the participant and delegated personnel. This consent form will include HIPAA authorization 
language which will also be reviewed with the participant.  The formal consent of a subject, using the IRB-approved 
consent form, will be obtained before that subject undergoes any study procedure.  The consent form must be 
signed by the subject or legally acceptable surrogate, and the investigator-designated research professional 
obtaining the consent. The participant will be consented in a private clinical space and will be given ample time to 
ask questions and have questions answered.  As the majority of the procedures that will occur are standard of care, 
we will clearly discuss what the research part of the day and days after will include. The voluntary nature of the 
study will be reviewed and participants will be told that should they choose not to consent, their clinical care will not 
be affected.  
11.4.1
Electronic Consent 
The Northwestern University IRB approved consent will be developed on the RedCap platform for electronic 
consent. RedCap is a secure, HIPAA compliant, web-based application for building and managing online data 
capture for research studies. The consent form built is in RedCap as a survey and mirrors that of the Northwestern 
University IRB approved consent. 
An email containing a link to the e-Consent will be sent to the patient’s email address provided by the participant or 
documented in EPIC. The email will include the research team’s contact information (phone, NM email) in case the 
subject has questions. The participant can choose to review the consent form with the coordinator over the phone 
or review independently. If the patient decides to participate s/he will complete the consent process by typing their 
name, date and sign using a mouse or touch screen (depending on device). The research team will receive an 
email notification when participant completes the consent process in RedCap and sign/date and follow-up with the 
participant to ensure all questions are addressed. 
A copy of the signed consent form will be sent in PDF format automatically upon participant’s signature, along with 
site contact information in case of questions. Subjects will also be informed they can request a paper copy be mailed 
to them. 
Use of eConsent provides the following patient benefits: 

Convenience – Where unnecessary, participants do not have to commute to the research site 

Less pressure – Participants can review the consent form on their own and with family without feeling 
pressure to sign right away 

More Informed – Subjects can take their time reading through the form thereby making a more informed 
decision
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12 Study Finances
12.1
Funding Source
This study is financed through a contract with Attune Medical.  Attune Medical is considered the funding sponsor 
who will provide financial support to conduct the study and the EnsoETM device free of charge.  
12.2
Conflict of Interest
All Northwestern University Investigators will follow the Northwestern University Policy on Conflicts of Interest 
Related to Research. 
12.3
Participant Stipends or Payments
Participants will not receive payment for their participation in this study. 
13 Publication Plan
Investigators will follow all Northwestern University applicable policies and guidelines relating to publishing study 
results. The research team will share materials planned for publication to the Funding Sponsor according to the 
terms of the Clinical Trial Agreement. 
14 References
1.
Calkins, H. et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and 
surgical ablation of atrial fibrillation. Hear. Rhythm 14, e275–e444 (2017).
2.
Halbfass, P. et al. Progression From Esophageal Thermal Asymptomatic Lesion to Perforation Complicating 
Atrial Fibrillation Ablation: A Single-Center Registry. Circ. Arrhythm. Electrophysiol. 10, e005233 (2017).
3.
Tschabrunn, C. M. et al. Comparison between single- And multi-sensor oesophageal temperature probes 
during atrial fibrillation ablation: Thermodynamic characteristics. Europace 17, 891–897 (2015).
4.
Arruda, M. S., Armaganijan, L., Biase, L. Di, Rashidi, R. & Natale, A. Feasibility and safety of using an 
esophageal protective system to eliminate esophageal thermal injury: Implications on atrial-esophageal 
fistula following AF ablation. J. Cardiovasc. Electrophysiol. 20, 1272–1278 (2009).
5.
Ahmed, H., et al. The esophageal effects of cryoenergy during cryoablation for atrial fibrillation. Heart 
Rhythm. 6, 962-969 (2009).  
6.
Levy, I. & Gralnek, I. M. Complications of diagnostic colonoscopy, upper endoscopy, and enteroscopy. Best 
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IRB #: STU00209610-MOD0003 Approved by NU IRB for use on or after 7/6/2020 through 6/7/2021.

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Data Collection Variables
Specific data elements to be recorded include:

Rhythm status at 3,6 and 12 months

Ablation technique utilized:
o
cryoablation for PVI only
o
cryoablation for PVI plus additional posterior wall ablation/isolation (PWI)
o
cryoablation with RF ablation for additional targets

Temperature settings of Gentherm Medical/Cincinnati Subzero Blanketrol III Hyper-Hypothermia 
System (confirm 42°C during cryoablation, and 4°C during RF ablation)

Temperature recordings from temperature probe used in control arm:
o
starting temperatures at each pulmonary vein
o
ending temperatures at each pulmonary vein
o
nadir temperatures at each pulmonary vein
o
additional temperatures at other targeted ablation points

Temperature probe alarm/overshoot settings (i.e., where is setpoint placed, or if manual probe 
used, what threshold is utilized to stop ablation)

Temperature probe alarm/overshoot frequency (total number, at all sensor points if multi-sensor 
probe is utilized)

Duration of pauses for alarms/overshoots

Additional delays encountered related to temperature probe positioning

Total fluoroscopy time

Total procedure length

Time of patient arrival, anesthesia, groin puncture, transseptal puncture, pulmonary vein block (for 
each vein), ablation catheter removal, vascular site closure, case completion, patient extubation

Total number of freezes, quantity/presence of contrast around cryoballoon, duration of each freeze 
at each vein, and temperature nadir at each freeze
IRB #: STU00209610-MOD0003 Approved by NU IRB for use on or after 7/6/2020 through 6/7/2021.