An Initial Assessment of the Safety and Performance of the Sphere-9™ Catheter and System for Mapping and Ablation of Atrial Arrhythmias
Conditions: Atrial Fibrillation, Atrial Flutter
Sponsor: Medtronic Cardiac Ablation Solutions

 
 
Protocol CP00001A Revision 2  
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Affera 
Document number CP-00004-A 
 
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AN INITIAL ASSESSMENT OF SAFETY AND PERFORMANCE OF 
THE SPHERE-9™ ABLATION CATHETER AND SYSTEM FOR 
MAPPING AND ABLATION OF ATRIAL ARRHYTHMIAS  
 
 
Protocol CP-00001A 
Revision 2 
(Document number CP-00004-A) 
 
 
January 29, 2019 
 
 
 
 
SPONSOR 
Affera, Inc. 
44 Pleasant St, Ste 200 
Watertown, MA 02472 
USA 
 
 
 
 
 
DISCLOSURE STATEMENT 
This document contains information that is confidential and proprietary to Affera, Inc.  This 
information is being provided to you solely for the purpose of evaluating or conducting a clinical 
study for Affera.  You may disclose the contents of this document only to study personnel under 
your supervision who need to know the contents for this purpose and to your Ethics Committee 
(EC), otherwise the contents of this document may not be disclosed without the prior 
authorization from Affera.  The foregoing shall not apply to disclosure required by governmental 
regulations or laws.  Any supplemental information that may be added to this document also is 
confidential and proprietary to Affera and must be kept in confidence in the same manner as the 
contents of this document. 
 

 
 
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INVESTIGATOR’S AGREEMENT 
 
 
I have read this Investigational Plan and agree to adhere to the requirements.  I will provide 
copies of this Investigational Plan and all pertinent information to all site personnel involved in 
this study.  I will discuss this material with them and ensure they are fully informed regarding the 
study products and the conduct of the study. 
 
I agree to conduct the study as outlined in the Investigational Plan, in accordance with the signed 
clinical study agreement and to the ethical principles stated in the latest version of the 
Declaration of Helsinki (2013), the applicable guidelines for good clinical practices, MEDDEV 
2.7/4 (Guidelines on Clinical investigations: a guide for manufacturers and notified bodies) and 
2.7/3 (Clinical investigations: serious adverse event reporting), ISO 14155:2011 (Clinical 
Investigation of Medical Devices for Human Subjects – Good Clinical Practice), or the 
applicable local and international regulations, whichever provide the greater protection of the 
individual.  In addition, I agree to provide all the information requested in the Case Report Forms 
presented to me by the Sponsor in a manner to assure completeness, legibility and accuracy.   
 
I also agree that all information provided to me by the Sponsor, including pre-clinical data, 
protocols, Case Report Forms, and any verbal and written information, will be kept strictly 
confidential and confined to the clinical personnel involved in conducting the study. It is 
recognized that this information may be relayed in confidence to the Ethics Committee.   
 
In addition, no reports or information about the study or its progress will be provided to anyone 
not involved in the study other than the Sponsor, the Ethics Committee, and competent 
authorities (if applicable).  Any such submission will indicate that the material is confidential. 
 
 
 
Principal Investigator’s Name (print) 
 
 
 
Title 
 
 
 
Address 
 
 
 
Signature / Date 
 
 
 
 

 
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STUDY SYNOPSIS 
 
PROTOCOL TITLE 
An Initial Assessment of Safety and Performance of the Sphere-
9™ Ablation Catheter and System for Mapping and Ablation of 
Atrial Arrhythmias 
  
INVESTIGATIONAL 
DEVICE 
 
Affera Sphere-9 Ablation Catheter with Affera Mapping and 
Ablation System 
 
POPULATION 
Subjects aged ≥ 18 and < 75 years presenting with atrial flutter 
(AFL), paroxysmal atrial fibrillation (AF) or persistent AF. 
 
STUDY DESIGN 
A prospective, single-arm, single center study in up to 30 patients. 
 
STUDY OBJECTIVES 
To evaluate the safety and performance of the Affera Sphere-9 
Ablation Catheter and the Affera Mapping and Ablation System. 
  
INCLUSION 
CRITERIA 
1. 
Age ≥ 18 and < 75 years. 
2. 
Suitable candidate for catheter non-emergent mapping and 
ablation of atrial flutter or atrial fibrillation as follows: 
 
x Atrial Flutter defined as 
o At least one episode of typical (clockwise or 
counterclockwise) atrial flutter documented by EKG, 
12 lead EKG, Holter or transtelephonic monitor, 
telemetry strip, or implanted device within 6 months 
prior to enrollment. 
 
OR  
 
x Atrial Fibrillation defined as 
o History of symptomatic paroxysmal and/or persistent 
atrial fibrillation within the past year documented by 
EKG  
AND  
o Failure of at least one class I-IV drug as evidenced by 
recurrent symptomatic AF, or intolerable to AAD. 
 
3. 
Subject is able and willing to give informed consent. 
4. 
Subject is able and willing, and has ample means to comply 
with all pre-, post- and follow-up testing requirements. 
EXCLUSION 
CRITERIA 
1. 
Documented left atrial thrombus or another abnormality 
which precludes catheter introduction. 
2. 
Documented ejection fraction (EF) < 40%. 

 
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3. 
Contraindication to anticoagulation therapy (heparin, 
warfarin, or novel oral anticoagulant [NOAC]). 
4. 
Unstable angina or ongoing myocardial ischemia. 
5. 
Myocardial infarction, unstable angina, cardiac surgery or 
coronary intervention within 3 months of enrollment. 
6. 
Congenital heart disease where the underlying abnormality 
increases the risk of the ablation. 
7. 
Pulmonary hypertension (mean pulmonary artery pressure 
[mPAP] > 50 mmHg) 
8. 
Enrollment in any other ongoing study protocol that would 
interfere with this study. 
9. 
Documented severely impaired kidney function defined as 
Cockcroft-Gault Glomerular Filtration Rate (GFR) < 
29ml/min. 
10. Active gastrointestinal (GI) bleeding. 
11. Active infection or sepsis. 
12. Short life expectancy (< 1 year) due to illness such as cancer, 
pulmonary, hepatic or renal disease. 
13. Significant anemia (defined as hemoglobin < 8.0 gr/dL). 
14. Severe uncontrolled systemic hypertension with systolic 
blood pressure (SBP) > 200 mm Hg within last 30 days. 
15. Severe bleeding, clotting or thrombotic disorder. 
16. Uncontrolled diabetes. 
17. Women who are pregnant or are not willing to use 
contraception for the duration of the study. 
18. Severe chronic obstructive pulmonary disease (COPD; 
identified by a forced expiratory volume [FEV1] <1) 
19. Prior stroke or TIA within the last 6 months. 
20. Any other condition that, in the opinion of the investigator, 
poses a significant hazard to the subject if an ablation 
procedure was performed. 
 
Additional exclusion criteria for AF patients only 
21. Left atrial diameter of > 55 mm (parasternal view).  
22. Prior atrial septal defect (ASD) or patent foramen ovale 
(PFO) closure with a device using a transcatheter 
percutaneous approach.  
23. Hypertrophic cardiomyopathy defined as left ventricular (LV) 
septal wall thickness >1.5cm.  
24. Prior ablation or surgery for atrial fibrillation.  
25. NYHA Class III or IV 
 
STUDY PROCEDURES 
Screening should be completed within 30 days of index ablation 
procedure.  Prior to screening, subjects will give informed consent.  
Initial screening will consist of review of relevant history including 
duration and frequency of arrhythmia(s), their subsequent 

 
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treatments (e.g., medications, previous ablation) and associated 
symptoms.  If the subject passes the initial screening, remaining 
screening tests will be performed which include assessment of 
study eligibility, concomitant medications, physical exam, 12 lead 
EKG, transthoracic echocardiography (TTE), urine pregnancy test 
(women of childbearing potential only), and optional CT and/or 
MR imaging. 
 
After confirmation of the absence of left atrial thrombus precluding 
catheter introduction, eligible subjects will undergo mapping and 
ablation. Esophageal evaluation, and CT and/or MR imaging may 
optionally be performed after treatment or during follow-up. 
 
Subjects will be followed for 365 days after the ablation procedure 
to characterize safety and product performance.  Note, the Day 10 
visit can be conducted by telephone. Ambulatory monitoring will 
be conducted within the follow-up windows at Day 90, Day 180 
and Day 365. Use of antiarrhythmic drugs (AADs) and other 
important cardiovascular drugs will be collected at every visit.  
Serious adverse events (AEs) will be collected starting on Day 0 
through study exit.  
  
SCHEDULE OF 
EXAMINATIONS 
Visit 1 - Screening (within 30 days) 
Visit 2 - Ablation (Day 0) 
Visit 3 - Day 10 ± 3 days (telephone call) 
Visit 4 - Day 90 ± 14 days  
Visit 5 - Day 180 ± 30 days  
Visit 6 - Day 365 ± 30 days  
 
STUDY OUTCOMES 
Safety: The primary safety outcome is the rate of the following 
serious adverse events (SAEs) occurring starting Day 0 and 
extending through the Day 10 assessment: transient ischemic 
attack; cerebrovascular accident; major bleeding; cardiac 
tamponade; pulmonary vein stenosis; severe pericarditis requiring 
extended hospitalization; myocardial infarction; diaphragmatic 
paralysis; atrio-esophageal fistula (through the Day 90 assessment); 
valvular damage; phrenic nerve palsy; intra-procedural device 
complications requiring open chest or heart surgery; vascular 
complications requiring surgical intervention; and death.    
 
Device performance: The primary product performance outcome is 
determined during the procedure and is defined as the following: 
x Catheter handling sufficient to reach reasonable intended 
targets, as determined by the physician: 
o 
catheter delivery to the desired cardiac chambers  
o 
manipulation of catheter  

 
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o 
completion of mapping procedure 
o 
safe removal of catheter from the subject 
x 3D electro-anatomical map creation and utility sufficient to aid 
diagnosis 
x Generation of acceptable acute therapeutic RF lesions 
 
The secondary product performance outcome is freedom from 
documented recurrence of the treated arrhythmia through the Day 
365 post-treatment follow-up visit.  In AF subjects, this includes 
freedom from documented AF, atrial tachycardia (AT), or AFL. 
 
ANALYSIS 
Descriptive statistics (N, mean, median, SD, minimum and 
maximum values for continuous variables, and the number and 
percentage of subjects in each category for categorical variables, 
where applicable) will be used to characterize study outcomes and 
safety parameters. 
 
 
The Schedules of Evaluations and Visits are located in Appendix 1. 

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TABLE OF CONTENTS
INVESTIGATOR’S AGREEMENT......................................................................................................... 2
STUDY SYNOPSIS ............................................................................................................................. 3
TABLE OF CONTENTS ....................................................................................................................... 7
ABBREVIATIONS ............................................................................................................................ 10
1.
INTRODUCTION ......................................................................................................................11
1.1.
Study Rationale......................................................................................................11
2.
DEVICE DESCRIPTION ............................................................................................................12
2.1.
Affera Sphere-9 Ablation Catheter ........................................................................12
2.2.
Affera Mapping System.........................................................................................13
2.3.
Affera RF Generator ..............................................................................................14
2.4.
Affera Irrigation Pump and Tubing Set .................................................................14
2.5.
Indications for Use.................................................................................................14
3.
GOOD CLINICAL PRACTICES (GCP) STATEMENT...................................................................14
4.
RISK-BENEFIT ANALYSIS.......................................................................................................15
5.
INVESTIGATIONAL PLAN........................................................................................................15
5.1.
Study Objectives ....................................................................................................15
5.2.
Study Design..........................................................................................................15
5.3.
Subject Population .................................................................................................17
5.3.1.
Inclusion Criteria......................................................................................17
5.3.2.
Exclusion Criteria.....................................................................................17
5.4.
Study Procedures ...................................................................................................18
5.4.1.
Informed Consent.....................................................................................18
5.4.2.
Subject Identification ...............................................................................19
5.4.3.
Visit 1: Screening (Day -30 to Day 0)......................................................19
Screen Failures.........................................................................19
5.4.4.
Visit 2: Day 0 – Index Ablation Procedure ..............................................20
5.4.5.
Visit 3: Day 10 ± 3 Days (Telephone call)...............................................20
5.4.6.
Visit 4: Day 90 ± 14 Days........................................................................20
5.4.7.
Visit 5: Day 180 ± 30 Days ......................................................................21
5.4.8.
Visit 6: Day 365 ± 30 Days ......................................................................21
5.5.
Study Completion ..................................................................................................21
5.5.1.
Completed Subjects..................................................................................21
5.5.2.
Discontinued Subjects ..............................................................................21
5.5.3.
Premature Study Termination ..................................................................22
5.6.
Investigational Device Accountability...................................................................22
5.7.
Prior and Concomitant Medication........................................................................22
6.
EXAMINATIONS AND EVALUATIONS ......................................................................................23
6.1.
Evaluations Conducted at Screening Only ............................................................23
6.1.1.
Demographics...........................................................................................23
6.1.2.
Medical History........................................................................................23

 
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6.1.3. 
Physical Exam ..........................................................................................23 
6.1.4. 
Hematology ..............................................................................................23 
6.1.5. 
Pregnancy Test (women of childbearing potential only) .........................23 
6.1.6. 
Optional CT or MR Imaging ....................................................................23 
6.2. 
Evaluations Conducted During the Study ..............................................................24 
6.2.1. 
12 Lead EKG ............................................................................................24 
6.2.2. 
Transthoracic Echocardiography (TTE) ...................................................24 
6.2.3. 
Concomitant Medications .........................................................................24 
6.2.4. 
Vital Signs ................................................................................................24 
6.2.5. 
Atrial Thrombus Screening ......................................................................24 
6.2.6. 
Optional Endoscopic Evaluation of the Esophagus .................................24 
6.2.7. 
Ambulatory Cardiac Monitoring ..............................................................24 
7. 
EVALUATION OF ADVERSE EVENTS AND DEVICE DEFICIENCIES ............................................25 
7.1. 
Adverse Events Definitions ...................................................................................25 
7.2. 
Assessment of Adverse Events ..............................................................................26 
7.3. 
Reporting/Recording of AEs..................................................................................27 
7.4. 
Adverse Events Requiring Expedited Reporting ...................................................27 
7.5. 
Anticipated Adverse Events ...................................................................................28 
7.6. 
Device Deficiencies ...............................................................................................30 
8. 
STATISTICAL METHODS .........................................................................................................31 
8.1. 
Sample Size Calculation ........................................................................................31 
8.2. 
Study Outcomes .....................................................................................................31 
8.2.1. 
Safety ........................................................................................................31 
8.2.2. 
Device Performance .................................................................................31 
8.3. 
Descriptive Analyses .............................................................................................32 
9. 
STUDY CONDUCT ...................................................................................................................32 
9.1. 
Ethics Committee (EC) ..........................................................................................32 
9.2. 
Competent Authority .............................................................................................32 
9.3. 
Informed Consent Process .....................................................................................33 
9.4. 
Confidentiality .......................................................................................................33 
9.5. 
Insurance ................................................................................................................33 
9.6. 
Protocol Deviations ................................................................................................34 
9.7. 
Study Monitoring and Source Documentation ......................................................34 
9.8. 
Protocol Amendments ............................................................................................35 
9.9. 
Record Keeping and Retention ..............................................................................35 
9.10. 
Investigator Final Report .......................................................................................35 
9.11. 
Study Report and Publication ................................................................................35 
10. 
REFERENCES ..........................................................................................................................37 
 
 
 
 
 

 
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FIGURES  
 
Figure 1 
Affera Sphere-9 Ablation Catheter ................................................................. 13 
 
 
 
TABLE OF APPENDICES 
 
Appendix 1. 
Schedule of Evaluations and Visits................................................................. 40 
Appendix 2. 
Investigator’s Responsibilities ........................................................................ 42 
Appendix 3. 
Sponsor’s Commitments ................................................................................. 45 
 
 

 
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ABBREVIATIONS 
 
AAD 
Antiarrhythmic Drug 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AF 
Atrial Fibrillation 
AFL 
Atrial Flutter 
ASD 
Atrial Septal Defect 
β-HCG 
Beta Human Chorionic Gonadotropin 
CBC 
Complete Blood Count 
COPD 
Chronic Obstructive Pulmonary Disease 
CPK 
Creatinine Phosphokinase 
CRF 
Case Report Form 
CRO 
Clinical Research Organization 
CS 
Clinically Significant 
CT 
Computed Tomography 
CVA 
Cerebrovascular Accident 
EC 
Ethics Committee 
EF 
Ejection Fraction 
EKG 
Electrocardiogram 
EGM 
Electrogram 
FDA 
Food and Drug Administration 
FEV 
Forced Expiratory Volume 
GCP 
Good Clinical Practices 
GFR 
Glomerular Filtration Rate 
GI 
Gastro-Intestinal 
Hgb 
Hemoglobin 
HCT 
Hematocrit 
HEENT 
Head, Eyes, Ear, Nose and Throat 
LV 
Left Ventricular  
mPAP 
mean Pulmonary Artery Pressure 
MR 
Magnetic Resonance 
NCS 
Not Clinically Significant 
NOAC 
Novel Oral Anticoagulant 
PFO 
Patent Foramen Ovale 
PI 
Principal Investigator 
QOL 
Quality of Life 
RBC 
Red Blood Cells 
RF 
Radiofrequency 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SBP 
Systolic Blood Pressure 
TIA 
Transient Ischemic Attack 
TTE 
Transthoracic Echocardiogram 
UADE 
Unanticipated Adverse Device Effect 
WBC 
White Blood Cells 
 
 

 
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1. 
INTRODUCTION 
Atrial fibrillation (AF) and flutter (AFL) affect tens of millions of people worldwide.  
These conditions are associated with increased risk of stroke and, in the case of atrial 
fibrillation, mortality. Catheter ablation using radiofrequency (RF) energy has become a 
widely accepted treatment for these tachyarrhythmias and is considered first-line therapy in 
some cases [1] [2].  
 
AF is a supraventricular tachycardia that manifests as a rapid, irregular atrial rhythm with 
no clearly-defined P-wave on the electrocardiogram. It affects an estimated 33 million 
people worldwide, and it carries significant risks. AF leads to dramatically increased risk of 
stroke, increased risk of heart failure, and increased mortality. Furthermore, AF is often 
symptomatic, leading to fatigue and reduced quality of life (QOL); however, it carries 
similar risks with or without symptoms [2].   
 
The success rate of catheter ablation for atrial fibrillation is superior to the efficacy of 
antiarrhythmic drugs. For example, the RAAFT-2 trial found that catheter ablation led to a 
55% recurrence rate for atrial fibrillation or atrial tachycardia at 2 years follow-up 
compared to 72% recurrence using antiarrhythmic drugs [2]. Ablation is also associated 
with a complication rate of 2-3% [4].   
 
Catheter ablation is a class I recommendation for the treatment of symptomatic drug-
refractory paroxysmal atrial fibrillation. Catheter ablation is considered a reasonable 
treatment for persistent atrial fibrillation as well as for paroxysmal atrial fibrillation prior to 
starting anti-arrhythmic drugs [2]. However, pulmonary vein reconnection is common, and 
repeat ablation is often necessary [2] [5]. 
 
Atrial flutter is a supraventricular tachycardia characterized by a rapid, organized atrial 
rhythm with clear P-waves on the electrocardiogram. Atrial flutter is less common than – 
and is usually accompanied by – atrial fibrillation [6] [2]. The incidence of atrial flutter 
increases rapidly with age over 50, affecting more than 5% of the population over 80 years 
of age, and it is significantly more common among men than women [6].  
 
Catheter ablation of atrial flutter is usually effective, with is a small risk of recurrent atrial 
flutter and also a risk of atrial fibrillation during follow-up [7]. RF catheter ablation is 
considered a relatively safe and effective procedure for the therapeutic treatment of typical 
atrial flutter [8]. Catheter ablation is a class I recommendation for many symptomatic atrial 
flutters, particularly when pharmacological treatment has failed [1]. However, repeat 
procedures are sometimes required to achieve long-term success [9].   
 
1.1. 
STUDY RATIONALE 
The application of durable RF ablation lesions remains an unmet need in catheter 
ablation for atrial fibrillation and flutter [2] [5] [9]. Nondurable lesions lead to 
electrical reconnection in the heart and the recurrence of the arrhythmia, requiring 
repeated treatment, or may create new arrhythmia circuits that may be more serious 
[1]. The Affera Sphere-9 Ablation Catheter and Affera Mapping and Ablation 
System have been developed to create safe and effective lesions in the heart.  

 
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The Affera Sphere-9 ablation catheter is an irrigated 8F bidirectional cardiac ablation 
catheter. The catheter employs an expandable ablation electrode that is designed to 
safely create durable lesions. Mounted on the ablation electrode are 9 mini surface 
electrodes that are used for detecting localized electrograms to aid in mapping and 
monitoring lesion formation. The local impedance of these surface electrodes is 
measured to provide the user with information regarding the proximity of each 
electrode to the tissue. In addition, each surface electrode contains a temperature 
sensor for providing localized surface temperature feedback, which allows tailored 
power titration.  
 
The Affera Mapping and Ablation System are designed for use with the Sphere-9 
catheter.  The system utilizes the added feedback information from the catheter to 
maximize RF delivery, and is designed to streamline the workflow of the mapping 
and ablation procedure. The Affera Mapping and Ablation System includes an RF 
generator with a user interface for controlling and monitoring energy delivery. It also 
includes a visualization interface for localizing the catheter, displaying electrograms, 
and constructing electroanatomical maps.  
 
With the combination of catheter handling, controlled lesion formation, and 
proximity and temperature feedback, the Sphere-9 Ablation Catheter and Affera 
Mapping and Ablation System are anticipated to safely and effectively treat a variety 
of arrhythmias. 
 
 
2. 
DEVICE DESCRIPTION 
 
2.1. 
AFFERA SPHERE-9 ABLATION CATHETER 
The Sphere-9 Ablation Catheter is a sterile, single-use 8F deflectable cardiac 
ablation and mapping catheter.  The Sphere-9 Ablation Catheter employs similar 
technology as commercially available cardiac ablation catheters, including catheter 
shaft materials, steering mechanism, location sensor, electrogram electrodes and 
irrigation.  The catheter features a unique expandable ablation electrode that 
provides a larger effective surface area for delivery of RF energy and allows for the 
placement of multiple discrete mini surface electrodes for collection of more 
localized electrogram and local impedance information than conventional ablation 
catheters.  Each surface electrode also contains a discrete temperature sensor, 
providing more localized temperature feedback than conventional ablation catheters. 
 
The catheter consists of a handle to control bidirectional deflection of the 7.5Fr 
steerable shaft.  The ablation electrode on the tip of the catheter expands to 9mm in 
diameter when deployed and collapses for introduction through an 8Fr introducer 
sheath.  Nine mini surface electrodes are mounted on the expandable ablation 
electrode and are spaced 5mm apart for recording highly localized electrograms.  
Each surface electrode is driven with a sensing current by the Mapping System in 
order to determine its Local Electrode Impedance, which can provide information to 

 
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the user regarding the proximity and orientation of the tip to the cardiac tissue.  Each 
surface electrode also contains a temperature sensor that reports localized 
temperature to the RF Generator.   The catheter contains an irrigation lumen that 
connects via a standard luer connector to irrigation solution (heparinized saline) 
provided by an irrigation pump and tubing set.  Irrigation provided from within the 
expandable ablation electrode reduces the likelihood of thrombus and coagulation.  
The catheter also contains passive electromagnetic location sensors in the tip and 
shaft to allow localization by the Mapping System. 
 
 
Figure 1 Affera Sphere-9 Ablation Catheter 
 
 
 
2.2. 
AFFERA MAPPING SYSTEM 
The Affera Mapping System is a computerized storage and display system with 
embedded software which is designed to present the user with information regarding 
the state and location of a cardiac catheter within the body.  The system can 
determine and present the 3-dimensional location of the catheter within the heart 
using the catheter’s electromagnetic location sensor.  The location information can 
be used to create a geometric shell representing chamber anatomy in which a virtual 
representation of the catheter can be displayed in real time in order to aid navigation 
of the catheter.  The system can also tag location points of interest for reference.  
Additionally, the system employs an impedance measurement system to measure 
and display the local impedance of surface electrodes on the Sphere-9 catheter, 
which can be used as an aid to assess electrode proximity and contact with tissue.  
The state of impedance of individual electrodes may be presented on a graphical 
display. 
 

 
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The Mapping System collects and displays electrogram signals from intracardiac 
electrodes on the catheter and presents voltage data derived from these signals on the 
display, including overlaying the data on the geometric shell.  
 
2.3. 
AFFERA RF GENERATOR 
The Affera RF Generator is designed to supply RF energy to the Sphere-9 catheter to 
perform ablation of cardiac tissue.  The RF Generator monitors the RF energy 
delivery during therapy, including the catheter tip temperatures, circuit impedance, 
output voltage and current, and internal system performance.  The application of RF 
energy can be controlled to a target catheter tip temperature.  The RF Generator also 
monitors the contact quality of the disposable dispersive return electrodes to ensure 
sufficient electrode contact during therapy delivery.  Through a communication link 
with the Irrigation Pump, the RF Generator can monitor and control the irrigation 
flow rate prior to, during, and following ablation delivery. 
 
2.4. 
AFFERA IRRIGATION PUMP AND TUBING SET 
The Affera Irrigation Pump and a sterile single-use Tubing Set are used to deliver 
saline irrigation flow to the ablation catheter during RF energy delivery.  The Pump 
interfaces with the RF Generator via a communication link to enable automatic 
control of the irrigation flow rate prior to, during, and following ablation delivery.  
The communication link also allows for Pump status updates including notification 
of interruption of the irrigation flow due to air bubble detection or other fault 
conditions.  
 
Additional information involving the device and its components including pre-
clinical data can be found in the Investigator’s Brochure. 
 
2.5. 
INDICATIONS FOR USE 
The Affera Sphere-9 Ablation Catheter and the Affera Mapping and Ablation 
System are indicated for cardiac ablation and mapping (stimulation and electrogram 
recording) in patients with cardiac arrhythmia. 
 
 
 
 
3. 
GOOD CLINICAL PRACTICES (GCP) STATEMENT 
This trial will be conducted in compliance with the Investigational Plan, the signed clinical 
study agreement and with the ethical principles stated in the latest version of the 
Declaration of Helsinki (2013), the applicable guidelines for good clinical practices, 
MEDDEV 2.7/4 (Guidelines on Clinical investigations: a guide for manufacturers and 
notified bodies) and 2.7/3 (Clinical investigations: serious adverse event reporting), EN 
ISO 14155:2012 (Clinical Investigation of Medical Devices for Human Subjects – Good 
Clinical Practice), or the applicable local and international regulations, whichever provide 
the greater protection of the individual.  Any deviations from the Investigational Plan that 

 
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may affect the safety and welfare of study participants will be immediately reported to the 
Sponsor and to the Ethics Committee (EC) per each institution’s guidelines. 
 
 
 
4. 
RISK-BENEFIT ANALYSIS 
The anticipated adverse events associated with cardiac ablation procedures include events 
reported in the literature related to catheter procedures, events identified in the risk and 
hazard analyses, and events associated with percutaneous interventions, and therefore 
represent the risks associated with participation in the trial.  A list of anticipated adverse 
events is defined in the Anticipated Adverse Events Section 7.5 of this document. 
 
Potential device malfunctions and potential user errors have been identified in the Hazard 
Analysis and Failure Modes and Effects Analysis exercises conducted in accordance with 
ISO 14971.  These are technical complications that may occur with the devices.  Mitigating 
steps to address each of the potential device malfunctions and potential user errors have 
been implemented to reduce the risks as low as possible.  No residual risks remain that are 
higher than the risks associated with the use of currently available conventional cardiac 
mapping and ablation tools.   
 
Overall potential patient benefits include reduction in symptomatic episodes of arrhythmia, 
similar to currently available cardiac ablation systems.  Potential patient risks include 
adverse events and potential device malfunctions and potential user errors similar to those 
associated with commercially available cardiac ablation systems.   
 
It is believed that the potential risks to a patient participating in this study should be similar 
to other RF ablation systems for the treatment of AF. Eligibility criteria that exclude 
patients who are at higher risk for experiencing an anticipated adverse event have been 
selected to reduce the potential risks to patients participating in this study.    
 
 
 
5. 
INVESTIGATIONAL PLAN 
 
5.1. 
STUDY OBJECTIVES 
The objectives of this study are to evaluate the safety and performance of the 
Sphere-9 Ablation Catheter and the Affera Mapping and Ablation System. 
 
5.2. 
STUDY DESIGN 
This is a prospective, single-arm, single center study involving the Affera Sphere-9 
Ablation Catheter and the Affera Mapping and Ablation System in up to 30 patients.  
The arrhythmias treated in this study are common atrial arrhythmias: atrial flutter 
(AFL), paroxysmal atrial fibrillation (AF), and persistent atrial fibrillation.   
 
The primary safety outcome is the rate of the following serious adverse events 
(SAEs) occurring starting Day 0 and extending through the Day 10 assessment: 

 
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transient ischemic attack; cerebrovascular accident; major bleeding; cardiac 
tamponade; pulmonary vein stenosis; severe pericarditis requiring extended 
hospitalization; myocardial infarction; diaphragmatic paralysis; atrio-esophageal 
fistula (through the Day 90 assessment); valvular damage; phrenic nerve palsy; intra-
procedural device complications requiring open chest or heart surgery; vascular 
complications requiring surgical intervention; and death.   
 
The primary product performance outcome is determined during the procedure and 
includes catheter handling, 3D electro-anatomical map creation and utility sufficient 
to aid diagnosis, and generation of acceptable acute therapeutic RF lesions.   
 
The secondary product performance outcome is freedom from the treated arrhythmia 
detected by ambulatory monitoring or ICD interrogation at the Day 90, Day 180, and 
Day 365 Visits.  In AF subjects, this includes freedom from documented AF, AT, or 
AFL. 
 
Pre-screening, i.e., medical record review without obtaining informed consent, is 
allowed. 
 
Initial Screening Activities. After providing informed consent, initial screening 
consisting of review of relevant history including duration and frequency of 
arrhythmia(s), their subsequent treatments (e.g., medications, previous ablation) and 
associated symptoms will be performed. 
 
If the subject passes the initial screening, remaining screening tests will be 
performed which include assessment of study eligibility, demographics, concomitant 
use of antiarrhythmic drugs (AADs) and other important cardiovascular drugs, 
physical exam, vital signs, 12 lead EKG, hematology, transthoracic 
echocardiography (TTE), urine pregnancy test (women of childbearing potential 
only), and optional CT and/or MR imaging  
 
After confirmation of the absence of atrial thrombus precluding catheter 
introduction, eligible subjects will undergo mapping and ablation.  Subjects will be 
assessed for potential adverse events prior to discharge.  Esophageal evaluation, and 
CT and/or MR imaging may optionally be performed after treatment or during 
follow-up. 
 
Subjects will be followed for approximately 365 days after the ablation procedure to 
characterize safety and product performance.  Note, the Day 10 visit can be 
conducted by telephone.  Ambulatory monitoring for a minimum of 48 hours will be 
conducted within the follow-up windows at Day 90, Day 180, and Day 365.  Use of 
antiarrhythmic drugs and other important cardiovascular drugs will be collected at 
every visit.  Serious adverse events (AEs) will be collected starting on Day 0 through 
study exit.   
 
A summary of the schedules of evaluations and visits can be found in Appendix 1. 

 
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5.3. 
SUBJECT POPULATION 
Up to a total of 30 subjects meeting the following study entry criteria will be treated.    
 
5.3.1. 
INCLUSION CRITERIA 
Subjects must satisfy all inclusion criteria to be included in the study: 
 
1. Age ≥ 18 and < 75 years. 
2. Suitable candidate for catheter non-emergent mapping and ablation of atrial 
flutter or atrial fibrillation as follows: 
 
x Atrial Flutter defined as 
o At least one episode of typical (clockwise or counterclockwise) atrial 
flutter documented by EKG, 12 lead EKG, Holter or transtelephonic 
monitor, telemetry strip, or implanted device within 6 months prior to 
enrollment. 
OR 
x Atrial Fibrillation defined as 
o History of symptomatic paroxysmal and/or persistent atrial 
fibrillation within the past year documented by EKG 
AND 
o Failure of at least one class I-IV drug as evidenced by recurrent 
symptomatic AF, or intolerable to AAD. 
 
3. Subject is able and willing to give informed consent. 
4. Subject is able and willing, and has ample means to comply with all pre-, post- 
and follow-up testing requirements. 
 
5.3.2. 
EXCLUSION CRITERIA 
Subjects will not be eligible for the study if any of the following criteria are present: 
 
1. 
Documented left atrial thrombus or another abnormality which precludes 
catheter introduction. 
2. 
Documented ejection fraction (EF) < 40%. 
3. 
Contraindication to anticoagulation therapy (heparin, warfarin, or novel oral 
anticoagulant [NOAC]). 
4. 
Unstable angina or ongoing myocardial ischemia. 
5. 
Myocardial infarction, unstable angina, cardiac surgery or coronary 
intervention within 3 months of enrollment. 
6. 
Congenital heart disease where the underlying abnormality increases the risk of 
the ablation. 
7. 
Pulmonary hypertension (mean pulmonary artery pressure [mPAP] > 50 
mmHg) 
8. 
Enrollment in any other ongoing study protocol that would interfere with this 
study. 

 
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9. 
Documented severely impaired kidney function defined as Cockcroft-Gault 
Glomerular Filtration Rate (GFR) < 29ml/min. 
10. Active gastrointestinal (GI) bleeding 
11. Active infection or sepsis. 
12. Short life expectancy (< 1 year) due to illness such as cancer, pulmonary, 
hepatic or renal disease. 
13. Significant anemia (defined as hemoglobin < 8.0 gr/dL). 
14. Severe uncontrolled systemic hypertension with systolic blood pressure (SBP) 
> 200 mm Hg within last 30 days. 
15. Severe bleeding, clotting or thrombotic disorder. 
16. Uncontrolled diabetes. 
17. Women who are pregnant or are not willing to use contraception for the 
duration of the study. 
18. Severe chronic obstructive pulmonary disease (COPD; identified by a forced 
expiratory volume [FEV1] <1). 
19. Prior stroke or TIA within the last 6 months. 
20. Any other condition that, in the opinion of the investigator, poses a significant 
hazard to the subject if an ablation procedure was performed. 
 
Additional exclusion criteria for AF patients only: 
21. Left atrial diameter of > 55 mm (parasternal view). 
22. Prior atrial septal defect (ASD) or patent foramen ovale (PFO) closure with a 
device using a transcatheter percutaneous approach. 
23. Hypertrophic cardiomyopathy defined as left ventricular (LV) septal wall 
thickness >1.5cm. 
24. Prior ablation or surgery for atrial fibrillation. 
25. NYHA Class III or IV 
 
 
5.4. 
STUDY PROCEDURES 
Prior to recruitment of any subjects into the study, written approval of the protocol 
and informed consent must be obtained from the EC. 
 
5.4.1. 
INFORMED CONSENT 
The investigator will explain the study purpose, procedures, and subject’s 
responsibilities to the potential participant and/or legal representative.  Informed 
consent must be obtained from each subject prior to conducting any study related 
procedures including screening procedures that are not part of the standard of care at 
the institution.  The subject's willingness and ability to meet the follow-up 
requirements will be determined, and written informed consent will be obtained.  
The subject will sign and date the informed consent form.  The investigator will also 
sign and date the consent form.  The original informed consent form will be retained 
with the subject records; a copy will be provided to the subject or legal 
representative.   
 

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Following is a detailed list of study visits from screening to final follow-up and the 
required procedures/tests.  Methodologies for specific tests/procedures are described 
in Section 6.
5.4.2.
SUBJECT IDENTIFICATION
To maintain confidentiality, the subject’s name should not be recorded on any study 
document other than the informed consent form.  A subject is considered enrolled 
after informed consent has been obtained.  Each enrolled subject will be assigned a 
unique identifier in the following format: CP00001-XX-YYY.  CP00001 is the study 
number, XX is the 2-digit assigned site number, and YYY is the 3-digit sequential 
subject ID number starting with 001.  For example, the first subject at site 01 will be 
assigned CP00001-01-001.  Subject ID numbers will not be re-used (e.g., if the 
subject is determined to be a screen failure).   
5.4.3.
VISIT 1: SCREENING (DAY -30 TO DAY 0)
Screening should be completed within 30 days of the index ablation procedure.  Test 
results from routinely performed standard assessments may be used to determine 
eligibility.  Prior to screening, the subject will provide informed consent and then be 
initially screened by review of relevant medical history including duration and 
frequency of arrhythmia(s), their subsequent treatments (e.g., medications, previous 
ablation) and associated symptoms.
If initial screening criteria are met, screening will proceed.  Eligibility will be 
assessed sequentially, starting with the least invasive and least expensive tests as 
follows.  Results from each test / screening activity should be reviewed prior to 
proceeding to the next step.
x
Demographics
x
Concomitant use of AADs and other important cardiovascular drugs medications
x
Physical exam, including actual height
x
Vital signs
x
12 lead EKG
x
Labs:
o
Urine pregnancy test (for women of childbearing potential only)
o
Hematology
x
Transthoracic echocardiography (TTE)
x
Optional CT or MR imaging
SCREEN FAILURES
Subjects not meeting all study entry criteria will be designated as screen failures.  
End of study procedures will not be performed for these subjects, but their reason for 
ineligibility will be recorded on the Screening Log.  Screen failures are not counted 
towards to total study enrollment.

 
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5.4.4. 
VISIT 2: DAY 0 – INDEX ABLATION PROCEDURE 
After documenting concomitant use of AADs and other important cardiovascular 
medications and confirming the absence of atrial thrombus or another abnormality 
precluding catheter introduction, catheters are introduced percutaneously and 
advanced to the chamber of interest.  For left atrial procedures, if the esophagus is 
not mechanically deviated away from the left atrium, a temperature probe may be 
placed in the esophagus to monitor heating during the procedure.   
 
The heart chamber is mapped using the Affera Sphere-9 Ablation Catheter and the 
Affera Mapping System to generate a representation of the heart and to locate the 
areas of the heart that are creating or propagating problematic electrical signals that 
interfere with the proper rhythm.  In addition, pacing is used to identify the location 
of the phrenic nerve.   
 
Ablation using the Affera Sphere-9 Ablation Catheter and the Affera RF Generator 
is performed, and data regarding ablation delivery is recorded by the Affera 
Mapping System.  Procedural success is monitored by mapping and/or pacing to 
verify termination and non-inducibility of the arrhythmia (all subjects) and/or 
successful isolation of target pulmonary veins.  Any serious procedural adverse 
events (AEs) will be documented. 
 
Prior to discharge, the following will be documented: 
x Vital signs 
x 12-lead EKG 
x Serious adverse events (AEs) 
At the discretion of the investigator, the following assessments can be performed 
prior to discharge: 
x Transthoracic echocardiography (TTE) 
x Endoscopic evaluation of the esophagus 
x CT or MR imaging 
 
5.4.5. 
VISIT 3: DAY 10 ± 3 DAYS (TELEPHONE CALL) 
The following assessments will be performed, optionally via a telephone call: 
x Concomitant use of AADs and other important cardiovascular medications  
x Serious cardiovascular AEs 
 
5.4.6. 
VISIT 4: DAY 90 ± 14 DAYS  
The following assessments will be performed: 
x A minimum of 48 hours of ambulatory cardiac monitoring 
x Episodes of treated arrhythmia greater than 30 second in duration 
x Concomitant use of AADs and other important cardiovascular medications  
x 12 lead EKG 
x Serious cardiovascular AEs 
At the discretion of the investigator, CT or MR imaging can be performed at this 
visit. 

 
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5.4.7. 
VISIT 5: DAY 180 ± 30 DAYS  
The following assessments will be performed: 
x A minimum of 48 hours of ambulatory cardiac monitoring 
x Episodes of treated arrhythmia greater than 30 second in duration 
x Concomitant use of AADs and other important cardiovascular medications  
x 12 lead EKG 
x Serious cardiovascular AEs 
At the discretion of the investigator, CT or MR imaging can be performed at this 
visit. 
 
5.4.8. 
VISIT 6: DAY 365 ± 30 DAYS  
The following assessments will be performed: 
x A minimum of 48 hours of ambulatory cardiac monitoring 
x Episodes of treated arrhythmia greater than 30 second in duration 
x Concomitant use of AADs and other important cardiovascular medications  
x 12 lead EKG 
x Serious cardiovascular AEs 
At the discretion of the investigator, CT or MR imaging can be performed at this 
visit. 
 
All subjects will exit the study after the Day 365 visit. 
 
5.5. 
STUDY COMPLETION 
 
5.5.1. 
COMPLETED SUBJECTS 
Each subject in the study will be considered completed when all assessments through 
the Day 365 visit have been performed in accordance with the study protocol. 
 
5.5.2. 
DISCONTINUED SUBJECTS 
Any subject may voluntarily discontinue the study at any time without prejudice.  
The investigator may discontinue a subject from the study at any time if (s)he 
considers that remaining in the study compromises the subject’s health or the subject 
is not sufficiently cooperative.  In either event, reason(s) for discontinuation should 
be recorded. 
 
Possible reasons for study discontinuation include the following: 
x Adverse events (AEs) necessitating discontinuation from the study. 
x Repeat ablation with a non-study device. 
x Subject decision (specify). 
x Investigator decision (specify). 
x Other reason (specify). 
 

 
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The reasons for any subject discontinuation will be recorded on the study completion 
form of the study worksheets. If possible, subjects who withdraw prior to study 
completion will undergo the following: 
x 
12 lead EKG 
x 
AE assessment 
x 
Assessment of symptomatic episodes of the treated arrhythmia 
x 
Concomitant medications 
 
Lost to follow-up will only be considered at the Day 365 visit.  Other follow-up 
visits will be considered missed visits if the subject is unable to attend.  Every 
attempt must be made to have subjects complete the study.  The 
investigator/designee must do his/her best to contact the subject by phone at least 
twice.  If no response is obtained from the subject, the investigator/designee is 
encouraged to contact one of the subject’s relatives or his/her general practitioner.  
Documentation of these contacts must be recorded in the subject’s source.  
 
5.5.3. 
PREMATURE STUDY TERMINATION 
The Sponsor reserves the right to discontinue the study for any safety, ethical or 
administrative reason at any time. 
 
5.6. 
INVESTIGATIONAL DEVICE ACCOUNTABILITY 
Documentation of receipt, use and return of all Sphere-9 Ablation Catheters as well 
as the Affera Mapping and Ablation System must be maintained by the Principal 
Investigator (PI) or his/her designee.  Investigational devices are to be used only in 
accordance with this protocol and under supervision of the PI or a duly designated 
person.  It is the PI’s responsibility to ensure that all study devices are kept in a 
secure location, with access limited to individuals authorized by the investigator.  A 
record of all study devices received, used and returned must be maintained by the 
site until the conclusion of the study.  Following accountability of the study devices 
by the Sponsor or its designee, all unused study devices will be returned to the 
Sponsor/Designee as directed in writing by the Sponsor or designee for gross 
reconciliation. 
 
5.7. 
PRIOR AND CONCOMITANT MEDICATION 
All concomitant antiarrhythmic drugs (AAD) and other important cardiovascular 
medications (taken within 30 days of Day 0) will be recorded at each visit.  For each 
medication taken, the following information will be collected:  
 
x Medication trade or generic name; 
x Indication for which the medication was given; 
x Dose/strength, route, and frequency of administration; 
x Date started, and date stopped (or continuation at study exit). 
 
 
 
 

 
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6. 
EXAMINATIONS AND EVALUATIONS 
 
6.1. 
EVALUATIONS CONDUCTED AT SCREENING ONLY 
 
6.1.1. 
DEMOGRAPHICS 
Date of birth, gender, race and ethnicity will be recorded. 
 
6.1.2. 
MEDICAL HISTORY 
Relevant medical history including duration and frequency of arrhythmia(s), their 
subsequent treatments (e.g., medications, previous ablation) and associated 
symptoms will be obtained at Screening.  All positive and negative findings will be 
carefully documented.  Any new finding discovered during the Screening evaluation 
and prior to the index ablation procedure will be considered to be part of the medical 
history and will not be recorded as an AE. 
 
6.1.3. 
PHYSICAL EXAM 
A physical exam will be performed at Screening.  The exam will include the 
following: head, eyes, ears, nose, and throat (HEENT), heart, lungs, abdomen, 
extremities, lymph nodes, musculoskeletal, neurological, and gastrointestinal 
systems.  Any abnormalities should be categorized as clinically significant (CS) or 
not clinically significant (NCS), and the abnormalities should be recorded.  Actual 
height will be measured. 
 
6.1.4. 
HEMATOLOGY  
Laboratory testing will be conducted by a local laboratory at each site at Screening.  
Hematology evaluation will include: complete blood count (CBC): red blood cells 
(RBC); hemoglobin (Hgb), hematocrit (HCT), platelets and white blood cells 
(WBC).  Abnormal readings will be considered to be part of the medical history and 
will not be recorded as an AE. 
 
6.1.5. 
PREGNANCY TEST (WOMEN OF CHILDBEARING POTENTIAL ONLY) 
For women of childbearing potential, a urine beta human chorionic gonadotropin (β-
HCG) test will be performed at Screening.  Results of the test must be negative.  
Confirmed menopause is defined as postmenopausal for ≥ 1 year. 
 
6.1.6. 
OPTIONAL CT OR MR IMAGING 
At the discretion of the investigator or the principal investigator, computed 
tomography (CT) or magnetic resonance (MR) imaging may be conducted during 
screening. Imaging may also be conducted at any time during the follow-up period.  
Any clinically significant abnormalities will be recorded. 
 
 
 
 
 

 
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6.2. 
EVALUATIONS CONDUCTED DURING THE STUDY 
 
6.2.1. 
12 LEAD EKG 
A 12-lead electrocardiogram (EKG) will be conducted.  The EKG recording will be 
printed out, and a copy will be placed with subject records.  Any clinically 
significant abnormalities will be recorded. 
 
6.2.2. 
TRANSTHORACIC ECHOCARDIOGRAPHY (TTE) 
A TTE will be conducted at Screening, and may be conducted at the physician’s 
discretion prior to Discharge following the ablation procedure if indicated.  At 
screening, measurements will include EF, LV septal wall thickness (AF patients 
only), estimation of mPAP, and assessment of left atrial thrombus to the extent 
possible (AF patients only).  Prior to Discharge following the ablation procedure, 
TTE may be used to assess pericardial effusion.  Any (structural) abnormalities 
should be categorized as clinically significant (CS) or not clinically significant 
(NCS), and the abnormalities should be recorded. 
 
6.2.3. 
CONCOMITANT MEDICATIONS 
Concomitant AADs and other important cardiovascular medications will be recorded 
at each visit using the trade name or generic name as described in Section 5.7. 
 
6.2.4. 
VITAL SIGNS 
Vital signs consisting of blood pressure (while subject is sitting), temperature, 
weight, heart rate, and respiratory rate will be measured. 
 
6.2.5. 
ATRIAL THROMBUS SCREENING 
Prior to the ablation procedure, transesophageal echocardiography (TEE) will be the 
preferred method to assess left atrial thrombus (for left atrial procedures) and 
spontaneous echo contrast.  Alternatively, if the subject has been on continuous 
anticoagulation for at least 3 weeks prior to the procedure, intracardiac 
echocardiography (ICE) may be used to assess cardiac thrombus and spontaneous 
echo contrast.  Any abnormalities should be categorized as clinically significant (CS) 
or not clinically significant (NCS), and the abnormalities should be recorded. 
 
6.2.6. 
OPTIONAL ENDOSCOPIC EVALUATION OF THE ESOPHAGUS 
At the discretion of the investigator, endoscopic evaluation of the esophagus 
(gastroscopy) may be conducted to evaluate the extent of esophageal ulceration.  
Any abnormalities should be categorized as clinically significant (CS) or not 
clinically significant (NCS), and the abnormalities should be recorded. 
 
6.2.7. 
AMBULATORY CARDIAC MONITORING  
Within the Day 90, Day 180, and Day 365 follow-up windows, each subject will be 
monitored for a minimum of 48 hours with an ambulatory cardiac monitor.  
Episodes of atrial fibrillation, atrial flutter, or atrial tachycardia lasting longer than 
30 seconds will be noted.    
 

 
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7. 
EVALUATION OF ADVERSE EVENTS AND DEVICE DEFICIENCIES 
 
7.1. 
ADVERSE EVENTS DEFINITIONS 
An adverse event (AE) is the development of an untoward medical occurrence or 
the deterioration of a pre-existing medical condition following or during exposure to 
an investigational medical device, whether or not considered causally related to the 
investigational medical device.   
 
An untoward medical condition can be symptoms (e.g., nausea, chest pain), signs 
(e.g., tachycardia, enlarged liver) or clinically significant abnormal results of an 
investigation (e.g., laboratory findings, electrocardiogram). 
 
Conditions or diseases that are chronic but stable should not be recorded as an AE.  
Changes in a chronic condition or disease that are consistent with natural disease 
progression are NOT considered AEs and should not be recorded.  These medical 
conditions should be adequately documented in the subject’s medical history.  
However, medical conditions present at enrollment that worsen in intensity or 
frequency in a manner inconsistent with the natural course of the disease during the 
treatment or post-treatment periods should be reported and recorded as AEs. 
 
A recurrence of the treated arrhythmia requiring hospitalization in order to administer 
cardioversion prior to the Day 90 visit is within the scope of treatment for chronic but 
stable AF patients.  This will not be considered an adverse event. 
 
A serious adverse event (SAE) is any untoward medical occurrence which: 
x Results in death permanent impairment of a body function or permanent damage 
to a body structure; 
x Results in serious deterioration in the subject’s health that either: 
x 
Is life-threatening; 
x 
Requires inpatient hospitalization (admission to hospital with a stay > 24 
hours) or prolongation of hospitalization which is not specifically required 
by the protocol or is elective; 
x 
Results in permanent impairment of a body function or permanent damage 
to a body structure; or 
x 
Requires medical or surgical intervention to preclude permanent impairment 
of a body function or permanent damage to a body structure. 
 
Additionally, important medical events that may not result in death, be life-
threatening or require hospitalization may be considered SAEs when they jeopardize 
the subject or require medical or surgical intervention to prevent one of the serious 
outcomes listed above.  
 
Adverse device effect (ADE) is an AE related to the use of an investigational medical 
device.  Note, this definition includes AEs resulting from insufficient or inadequate 
instructions for use, operation, or any malfunction of the investigational medical device.  

 
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In addition, this definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
 
Serious adverse device effect (SADE) is an ADE that that has resulted in any of the 
consequences characteristic of a SAE. 
 
An unanticipated adverse device effect (UADE) is defined as 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 predicate devices, or any 
other unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects. 
 
7.2. 
ASSESSMENT OF ADVERSE EVENTS 
The need to capture AEs is not dependent upon whether or not the clinical event is 
associated with the use of the study device or procedure.  All AEs, regardless of 
severity, occurring at the index ablation through study exit visit must be recorded.  
Events occurring prior to the endovascular procedure must be listed in the medical 
history. 
 
The following information should be obtained for each AE: 
 
1. Event description.  Every effort must be made to report the underlying condition 
or unifying diagnosis for the event.  To avoid vague, ambiguous or colloquial 
expressions, the AE should be recorded in standard medical terminology rather than 
the subject’s own words when possible.  Signs and symptoms that are considered 
unrelated to an encountered syndrome or disease should be recorded as individual 
AEs on the CRF (e.g., if congestive heart failure and severe headache are observed at 
the same time, each event should be recorded as an individual AE).   
 
In addition, AEs occurring secondary to other events (e.g., sequelae) should be 
identified by the primary cause (i.e., a "primary" AE, if clearly identifiable, generally 
represents the most accurate clinical term to record on AE CRF; events occurring 
secondary to the primary event should be described in the narrative description of 
the case [e.g., example: orthostatic hypotension → fainting and fall to floor → head 
trauma →neck pain; the primary AE is orthostatic hypotension]). 
 
2. Duration: The date of onset and date of resolution should be reported.  Every 
effort should be made to capture the exact dates. 
 
3. Outcome: The final status of the event should be reported as resolved, ongoing, 
or if it resulted in death.  If the event is present at the final study visit, the ongoing 
box must be marked.  
 
4. Severity: The worst severity of the event must be reported as mild, moderate, or 
severe using the following definitions: 

 
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x Mild: Aware of sign or symptom, but easily tolerated 
x Moderate: Discomfort enough to cause interference with usual activity 
x Severe: Incapacitating with inability to work or do usual activity 
 
5. Action taken: Treatment of the event may be reported as none, medical and/or 
surgical.  
 
6. Seriousness: Determined by using the criteria in Section 7.1. 
 
7. Relationship to device (study device or ancillary device), and procedure.  The 
relationship to device and study procedure will be assessed using the following 
criteria. 
 
x Not related: no temporal association, or the cause of the event has been 
identified; or the device or procedure cannot be implicated 
x Unlikely: the relationship with the use of the device seems not relevant 
and/or the event can be reasonably explained by another cause, but additional 
information may be obtained 
x Possible: temporal association, but other etiologies are likely to be the cause; 
however, involvement of the device or procedure cannot be excluded 
x Probable: the relationship with the use of the investigational device seems 
relevant and/or the event cannot reasonably be explained by another cause, 
but additional information may be obtained 
x Causal: temporal association; other etiologies are possible, but unlikely 
 
If any AE is considered to be “possibly related” or “related” to the use of the study 
device, that event will classed as an ADE or a SADE. 
 
7.3. 
REPORTING/RECORDING OF AES 
Throughout the course of the study, all efforts will be made by the investigator to 
remain alert to possible AEs.  The first concern will be the safety of the subject, and 
for providing appropriate medical intervention.  The period of observation for 
collection of AEs starts at index ablation procedure until study exit.  Any AE should 
be recorded on the appropriate study worksheet. 
 
7.4. 
ADVERSE EVENTS REQUIRING EXPEDITED REPORTING 
The Investigator will report all SAEs and device deficiencies that could have led to a 
SADE; this information shall be promptly followed by detailed written reports [EN 
ISO 14155:2012 § 9.8 b].   
 
The Investigator will document all SAEs and SADEs, including device deficiencies 
in the study subject’s file and report it to the Sponsor and to the Clinical Research 
Organization (CRO) within 24 hours of knowledge of event.  When medical reports 
(lab results, examinations, etc.) associated with AEs are submitted to the Sponsor or 

 
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CRO, all personal subject information (name, address, etc.) must be removed or 
redacted.  The redacted materials must be identified only with the subject ID 
number. 
 
Upon notification of SAEs, the Sponsor will initiate and complete a review and 
evaluation of the event within time frames that will maintain reporting compliance 
with applicable regulatory agencies.  The Sponsor is responsible for classification 
and reporting of AEs and ongoing safety evaluation of the clinical investigation in 
line with EN ISO 14155:2012 and regulatory requirements.  If insufficient 
information is available to reach a definitive diagnosis, the Sponsor may instruct the 
monitor responsible for the site to contact the site to request additional confirmatory 
information, if any.   
 
In the event of a subject’s death, the Investigator will make reasonable effort to 
obtain a copy of the autopsy report and/or death summary.  The Investigator will 
determine the cause of death and its relationship to the investigational device; the 
Investigator will record results on the AE case report form (CRF).  The Investigator 
will include copies of an autopsy report, if available, and/or a death summary with 
this form.  
 
The Investigator is responsible for reporting all SAEs, SADEs, and device 
deficiencies that could have led to a SADE to the EC, according to national 
regulations and EC requirements.  The investigator will forward a copy of this report 
to the Sponsor and file it in the site regulatory binder.  
 
The Sponsor will ensure that its Authorized Representative will report all SAEs and 
device deficiencies that could have led to an SADE to the Competent Authorities in 
accordance with European Medical Devices directives and all applicable national 
regulations. 
 
7.5. 
ANTICIPATED ADVERSE EVENTS 
Anticipated complications/AEs are defined as complications/events that can be 
reasonably associated with catheter ablation procedures.   
 
Anticipated AEs include, but are not limited to: 
x 
Air embolism 
x 
Allergic reaction (including anaphylaxis) 
x 
Anesthesia reaction 
x 
Angina 
x 
Aorto-right atrial fistula 
x 
Arrhythmias, including exacerbation of pre-existing atrial fibrillation 
x 
Arterial-venous fistula 
x 
Cardiac perforation/ tamponade 
x 
Cardiac thromboembolism 
x 
Cardiac or respiratory arrest 
x 
Catheter entrapment 

 
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x 
Cerebrovascular incident / Stroke 
x 
Chest pain/discomfort 
x 
Congestive heart failure 
x 
Coronary artery dissection 
x 
Coronary artery spasm 
x 
Coronary artery thrombosis / occlusion 
x 
Death 
x 
Diaphragmatic paralysis 
x 
Dislodgement of ICD or permanent pacing leads  
x 
Endocarditis 
x 
Esophageal ulceration 
x 
Gastroparesis 
x 
Heart failure / pump failure 
x 
Hemoptysis 
x 
Hemoptysis 
x 
Hemothorax 
x 
Hypotension 
x 
Hospitalization (initial and prolonged) 
x 
Increased creatinine phosphokinase (CPK) level 
x 
Infections 
x 
Laceration 
x 
Leakage of air or blood into the lungs or other organs due to perforation 
x 
Left atrial esophageal fistula 
x 
Major bleeding, requiring surgery or transfusion 
x 
Myocardial infarction 
x 
Obstruction or perforation or damage to the vascular system 
x 
Pericarditis 
x 
Pericardial effusion 
x 
Phrenic nerve damage including Diaphragmatic paralysis 
x 
Pleural effusion  
x 
Pneumonia 
x 
Pneumothorax  
x 
Pulmonary edema 
x 
Pulmonary embolism 
x 
Pulmonary vein dissection 
x 
Pulmonary vein thrombus 
x 
Pulmonary hypertension 
x 
Respiratory depression 
x 
Skin burns 
x 
Severe PV stenosis or complete occlusion, even asymptomatic  
x 
Tamponade, potentially requiring surgery 
x 
Temperature elevation or fever 
x 
Transient Ischemic Attack (TIA) 
x 
Thromboembolism 

 
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x 
Thrombosis 
x 
Unintended complete or incomplete AV, Sinus node, or other heart block or 
damage 
x 
Valve damage 
x 
Vascular bleeding / local hematomas / ecchymosis 
x 
Vasovagal reactions 
x 
Ventricular tachyarrhythmia 
x 
Volume overload 
 
7.6. 
DEVICE DEFICIENCIES 
Device deficiency is defined as an inadequacy of a medical device with respect to its 
identity, quality, durability, reliability, safety or performance.   
 
Note, device deficiencies include malfunctions, use errors, and inadequate labelling.  
All device deficiencies or malfunctions that occur during the course of the trial and 
could have led to an SAE must be reported, whether or not they were associated with 
an AE. 
 
Device malfunction: failure of an investigational medical device to perform in 
accordance with its intended purpose when used in accordance with the instructions 
for use. 
 
User error: act or omission of an act that results in a different medical device 
response than intended by the manufacturer or expected by the user. 
 
The Device Deficiency CRF is specific for reporting all device deficiencies, or 
malfunctions that occur during the course of the trial, whether or not they were 
associated with an adverse event.  Device Deficiency CRFs should be submitted to 
the Sponsor and CRO within 24 hours of the occurrence defining the device 
deficiency.   
 
Anticipated device deficiencies and malfunctions include but are not limited to:  
x 
Catheter deflection deficiency or failure 
x 
Malfunction of a catheter electrode 
x 
Malfunction of a catheter temperature sensor 
x 
Unexpected termination of ablation due to internal system error 
x 
Failure to initiate ablation due to internal system error 
x 
Temporary or sustained loss of catheter navigation/visualization capability 
 
 
 
 
 
 
 

 
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8. 
STATISTICAL METHODS 
 
8.1. 
SAMPLE SIZE CALCULATION 
This trial is intended to demonstrate safety and performance of the device and 
system.  As a result, no formal statistical hypothesis was applied to derive to the 
sample size. 
 
8.2. 
STUDY OUTCOMES 
 
8.2.1. 
SAFETY 
The primary safety outcome is the rate of the following SAEs occurring starting Day 
0 and extending through the Day 10 follow-up visit:  
 
x 
TIA 
x 
CVA 
x 
Major bleeding 
x 
Cardiac tamponade 
x 
Pulmonary vein stenosis 
x 
Severe pericarditis requiring hospitalization 
x 
Myocardial infarction 
x 
Diaphragmatic paralysis 
x 
Atrio-esophageal fistula (through the Day 90 assessment) 
x 
Valvular damage 
x 
Phrenic nerve palsy 
x 
Intra-procedural device complications requiring open chest or heart surgery 
x 
Vascular complications requiring surgical intervention 
x 
Death 
 
8.2.2. 
DEVICE PERFORMANCE  
The primary product performance outcome is determined during the procedure, and 
is defined as the following: 
x 
Catheter handling sufficient to reach reasonable intended targets, as determined 
by the physician: 
o 
catheter delivery to the desired cardiac chambers  
o 
manipulation of catheter  
o 
completion of mapping procedure 
o 
safe removal of catheter from the subject 
x 
3D electro-anatomical map creation and utility sufficient to aid diagnosis 
x 
Generation of acceptable acute therapeutic RF lesions 
 
The secondary product performance outcome is freedom from documented 
recurrence of the treated arrhythmia detected by ambulatory monitoring at the Day 
90, Day 180, and Day 365 Visits.  In AF subjects, this includes freedom from 
documented recurrence of AF, AT, or AFL.  Recurrence is defined as any episode 
lasting longer than 30 seconds. 

 
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8.3. 
DESCRIPTIVE ANALYSES 
Continuous variables will be summarized using standard quantitative statistics: 
number of non-missing observations, mean, standard deviation, median, quartiles 
and range (minimum and maximum observed values).  The number of missing 
observations, if any, will also be summarized. 
 
Categorical variables will be summarized using classical frequency statistics: 
number of non-missing observations and percentages by categories.  Number and 
percent of missing data, if any, will also be summarized. 
 
 
 
 
 
9. 
STUDY CONDUCT 
 
9.1. 
ETHICS COMMITTEE (EC)  
Prior to the initiation of the study, the protocol, and the informed consent form will 
be submitted to the EC for approval.  By signing the clinical trial agreement, the 
investigator is assuring that an EC will be responsible for the initial and continuing 
review of the proposed clinical study.  A copy of the EC approval letter for the 
protocol, the informed consent, and the protocol signature page must be submitted to 
the Sponsor or its designee prior to release of investigational supplies to the study 
site.  The approval letter must refer to the specific protocol and the informed consent 
form.  Any Investigator who is also a member of the EC is not to participate in the 
protocol approval decision.  This non-participation must be noted in the approval 
letter.  The study site must maintain an accurate and complete record of all reports, 
documents and other submissions made to the EC concerning this protocol.   
 
Any report of withdrawal of EC approval will be submitted to the Sponsor or its 
designee within five (5) working days. 
 
9.2. 
COMPETENT AUTHORITY 
If needed, the study will be reviewed by the relevant Competent Authority as well.  
The Sponsor or its designee is responsible for obtaining regulatory approval for the 
study from the relevant Competent Authority.  No subjects may be enrolled in the 
study until written notification of such approval has been given by the Sponsor.  The 
Sponsor or its designee is responsible for reporting SAE and Device Deficiencies 
that might have led to a SADE as appropriate to the relevant Competent Authority.  
The Sponsor or its designee is responsible to provide the relevant Competent 
Authority with the study final report within 90 days of the study termination. 
 
The study will not start without the written approval of the EC and, where needed, 
the Competent Authority approval and after the completion of any other local 
regulation requirements.   
 

 
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9.3. 
INFORMED CONSENT PROCESS 
It is the responsibility of the Investigator to inform each subject or his/her legal 
representative, prior to the screening evaluation, of the purpose of this clinical trial, 
including possible risks and benefits and document the informed consent process in 
the subject’s chart.  Any changes made to the informed consent must be approved by 
the Sponsor or its designee, prior to submission to an EC.  After approval by the 
Sponsor or its designee, the informed consent must be submitted to and approved by 
an EC.  Prior to entry into the study or initiation of any study-related procedures, the 
subject or his/her legal representative must read, sign and date the informed consent 
form.  The person executing the consent must also sign and date the EC-approved 
consent form.  One original informed consent form is to be retained by the study site 
and a copy is to be given to the subject or his/her legal representative.  The informed 
consent process must be documented in the subject’s source/medical record. 
 
The informed consent must be written in a language in which the subject or his/her 
legal representative is fluent.  If a foreign language translation is required, a 
statement of certification of the translation must be issued.  Regulations require that 
foreign language informed consent forms be submitted to the EC for approval.  The 
investigator must forward a copy of the consent form, the certified foreign language 
translation and an EC approval letter to the Sponsor or its designee. 
 
9.4. 
CONFIDENTIALITY 
In accordance with GCP and with the national data protection laws, all information 
concerning the subjects in the study must be treated as strictly confidential by all 
persons involved in the study.   Health data will be recorded and forwarded to the 
Sponsor or its designee, participating EC and Competent Authorities, for evaluation 
as required.  Any information that is obtained in connection with this study that can 
be identified with the subjects will remain confidential.  Any data that may be 
published in scientific journals will not reveal the identity of the study participants 
 
The investigator acknowledges that any and all information acquired from the 
Sponsor or its designee or developed or acquired in connection with the study are 
strictly confidential.  The investigator will not disclose any confidential information 
to any third party nor use confidential information for any purpose without first 
obtaining the consent of Sponsor in writing.  Such consent shall be deemed to have 
been given for disclosure to any person for whom the investigator is responsible at 
his/her center, but only so far as required for the purposes of the study, and, in the 
case of disclosures to staff, only if such staff are bound by obligations of 
confidentiality no less strict than those set out herein. 
 
9.5. 
INSURANCE 
In order to cover possible damage to health, in relation to participation in this study, 
the Sponsor, has, as required by law, obtained appropriate insurance coverage. 
 
 
 
 

 
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9.6. 
PROTOCOL DEVIATIONS 
The Investigator is not allowed to deviate from the protocol without prior approval 
by the Sponsor and prior review and documented approval from the governing EC.   
 
Under emergency circumstances, deviations from the clinical investigation plan to 
protect the rights, safety and well-being of human subjects may proceed without 
prior approval of the Sponsor and the EC.  These deviations will be reported to the 
Sponsor and to the EC as soon as possible after detection, but no later than 24-hours 
from the time of the deviation. 
 
Deviations must be documented on the appropriate Protocol Deviation CRF.  If a 
Clinical Monitor becomes aware that an Investigator is not complying with the 
signed Investigator’s Agreement, the Investigational Plan, the requirements of ISO 
14155 or other applicable regulations, or any conditions of approval imposed by the 
reviewing EC, the Sponsor or designee will immediately either secure compliance or 
discontinue shipments of the investigational device to the Investigator and terminate 
the Investigator’s participation in the investigation.  The Investigator will be required 
to return all investigational components of the study device and system, unless this 
action would jeopardize the rights, safety or welfare of a patient. 
 
Protocol deviations will be analyzed by the Sponsor for the impact to the overall 
integrity of the study.  Disqualification is warranted when an Investigator has 
repeatedly or deliberately violated governing regulations or has repeatedly or 
deliberately submitted false information in any report.  Where protocol deviations 
occur, which do not warrant disqualification from a study, the Sponsor or designee 
will implement appropriate corrective and preventive actions, including repeat 
training as deemed necessary. 
 
9.7. 
STUDY MONITORING AND SOURCE DOCUMENTATION 
The Sponsor or its designee may meet with investigators prior to the initiation of the 
study in order to review the adequacy of the subject population, facilities, and 
equipment with respect to the needs of the study, and to familiarize the investigator 
with the study protocol.   
 
During the study, the clinical monitor will visit the study facilities regularly and 
utilize telephone and written communications on an ongoing basis to maintain 
current knowledge of the study.  During periodic visits to the study site, the monitor 
will review the source documents used for completion of the CRFs to verify the 
accuracy and completeness of the information contained in those reports in 
preparation for retrieval.  Source documents must contain all data entered in the 
CRFs.  Source documents may include a subject’s medical record, hospital charts, 
clinic charts, the Investigator’s study files, the results of diagnostic tests such as 
laboratory tests, EKGs, 24-hour Holter monitoring and the like.  All data generated 
during this study and the source documents from which they originated are subject to 
inspection by the Sponsor or its representatives and/or regulatory agencies. 
 

 
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Upon completion of the study, the clinical monitor will conduct a final visit (close-
out) to the site.  The objectives of this visit are to ascertain that all regulatory records 
and reports are complete, verify that investigational devices and other supplies have 
been accounted for and ensure that the investigator is aware of his/her 
responsibilities post-study. 
 
9.8. 
PROTOCOL AMENDMENTS 
The Sponsor will document modifications to the protocol in the form of a written 
amendment.  Protocol modifications that impact subject safety or the validity of the 
study must be approved by the EC before implementation.  In the case of a medical 
emergency, to remove immediate apparent hazard to subjects, a change may be made 
preferably after discussion with the Sponsor or its designee.  In these instances, the 
EC and, if applicable, Competent Authorities will be notified as soon as possible.  
 
9.9. 
RECORD KEEPING AND RETENTION 
Data generated for the study should be stored in a limited-access file area and be 
accessible only to representatives of the study site, the Sponsor and its 
representatives and relevant health authorities/regulatory agencies.  All reports and 
communications relating to study subjects will identify subjects only by initials and 
subject identification number.  Complete subject identification will be kept by the 
investigator.  This information will be treated with strict adherence to professional 
standards of confidentiality. 
 
All study-related records must be maintained for at least 5 years after study 
completion.   The Sponsor will notify the Investigator when records are no longer 
needed.  The Investigator will not discard any records without notifying the Sponsor.  
If the Investigator moves from the current investigational site, the Sponsor should be 
notified of the name of the person who will assume responsibility for maintenance of 
the records at the investigational site or the new address at which the records will be 
stored.  The Investigator will notify the Sponsor as soon as possible in the event of 
accidental loss or destruction of any study documentation. 
 
9.10. INVESTIGATOR FINAL REPORT 
The investigator shall provide the EC and the Sponsor with an accurate final report 
within 2 months after completion, termination or discontinuation of the study.  The 
final report may not precede final data submission which has not been monitored. 
 
9.11. STUDY REPORT AND PUBLICATION 
The results of the study may be submitted for publication.  Upon the prior written 
consent of Sponsor, Investigator shall have the rights to publish papers related to the 
Study. 
 
If written permission from the Sponsor is provided, the PI may publish and/or 
present the results of the Study conducted at their site, provided that, prior to any 
such publication or presentation, the site and/or the PI shall furnish the Sponsor with 
two (2) hard copies and one electronic copy of any materials intended for publication 

 
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or presentation at least sixty (60) days prior to the submission of manuscripts.  The 
Sponsor shall then have sixty (60) days from the receipt of such materials to review 
and provide the site and/or the PI with written comments. 
 
 
 
 

 
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10. REFERENCES 
 
[1] R. L. Page, J. A. Joglar, M. A. Caldwell, H. Calkins, J. B. Conti, B. J. Deal, N. M. Estes III, 
M. E. Field, Z. D. Goldberger, S. C. Hamill and J. H. Indik, "2015 ACC/AHA/HRS 
guideline for the management of adult patients with supraventricular tachycardia: a report of 
the American College of Cardiology/American Heart Association Task Force on Clinical 
Practice Guidelines and the Heart Rhythm Society," Heart Rhythm, vol. 13, no. 4, pp. e136-
e221, 2016.  
[2] H. Calkins, G. Hindricks, R. Cappato, Y. Kim, E. Saad, L. Aguinaga, J. Akar, V. Badhwar, 
J. Brugada, J. Camm and P. Chen, "2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert 
consensus statement on catheter and surgical ablation of atrial fibrillation," Heart Rhythm, 
vol. 14, no. 10, pp. e275-e444, 2017.  
[3] A. Verma, L. Macle, J. Cox and A. Skanes, "Canadian Cardiovascular Society atrial 
fibrillation guidelines 2010: catheter ablation for atrial fibrillation/atrial flutter," Canadian 
Journal of Cardiology, vol. 27, no. 1, pp. 60-66, 2011.  
[4] D. Callans, E. Gerstenfeld, S. Dixit, E. Zado, M. Vanderhoff, J. REN and F. Marchlinski, 
"Efficacy of repeat pulmonary vein isolation procedures in patients with recurrent atrial 
fibrillation," Journal of cardiovascular electrophysiology, vol. 15, no. 9, pp. 1050-1055, 
2004.  
[5] J. Granada, W. Uribe, P. Chyou, K. Maassen, R. Vierkant, P. Smith, J. Hayes, E. Eaker and 
H. Vidaillet, "Incidence and predictors of atrial flutter in the general population," Journal of 
the American College of Cardiology, vol. 36, no. 7, pp. 2242-2246, 2000.  
[6] H. Calkins, R. Canby, R. Weiss, G. Taylor, P. Wells, L. Chinitz, S. Milstein, S. Compton, K. 
Oleson, L. Sherfesee and J. Onufer, "Results of catheter ablation of typical atrial flutter," 
American Journal of Cardiology, vol. 94, no. 4, pp. 437-442, 2004.  
[7] M. Rodgers, C. McKenna, S. Palmer, D. Chambers, S. Van Hout, S. Golder, C. Pepper, D. 
Todd and N. Woolacott, "Curative catheter ablation in atrial fibrillation and typical atrial 
flutter: systematic review and economic evaluation," 2008. 
[8] M. Hsieh, C. Tai, C. Chiang, C. Tsai, W. Yu, Y. Chen, Y. Ding and S. Chen, "Recurrent 
atrial flutter and atrial fibrillation after catheter ablation of the cavotricuspid isthmus: a very 
long-term follow-up of 333 patients," Journal of Interventional Cardiac Electrophysiology, 
vol. 7, no. 3, pp. 225-231, 2002.  
 
 
 
 
 
 
 
 
 
 
 

 
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Rev CO 
Description of change 
 A 
CO-000964 
Release of Protocol CP-00001A revision 2: define as single 
center study; add ambulatory monitoring at 3,6 and 12 
months; add pacing to identify phrenic nerve; add 
gastroscopy; remove TTE from thrombus screening; update 
safety outcome to 10 days, exclude AF recurrence from 
AEs. 
 
 
 

 
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APPENDICES 
 
 
 
 

 
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Appendix 1. 
Schedule of Evaluations and Visits 
 
 

 
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SCHEDULE OF EVALUATIONS AND VISITS 
Visit 
Screening 
Day 0 
Ablation 
Procedure 
Day 0 
Discharge 
Day 10 ±  
3 days† 
Day 90 ± 
14 days 
Day 180 ± 
30 days 
Day 365 ± 
30 days 
Visit Number 
1 
2 
2 
3 
4 
5 
6 
Informed Consent 
9 
 
 
 
 
 
 
Demographics 
9 
 
 
 
 
 
 
Medical History 
9 
 
 
 
 
 
 
Concomitant Antiarrhythmic Drugs 
(AAD) and Other Important 
Cardiovascular Medications  
9 
9 
 
9 
9 
9 
9 
Inclusion/Exclusion 
9 
 
 
 
 
 
 
Physical Exam 
9 
 
 
 
 
 
 
Vital Signs 
9 
 
9 
 
 
 
 
12 lead EKG 
9 
 
9 
 
9 
9 
9 
Hematology 
9 
 
 
 
 
 
 
Urine Pregnancy Test* 
9 
 
 
 
 
 
 
Transthoracic Echocardiography 
Exam 
9 
 
9# 
 
 
 
 
Optional CT or MR imaging 
9# 
 
9# 
 
9# 
9# 
9# 
Atrial thrombus screening 
 
9 
 
 
 
 
 
Ablation  
 
9 
 
 
 
 
 
Endoscopic Evaluation of Esophagus 
 
 
9# 
 
 
 
 
Serious Adverse Events  
 
9 
9 
9 
9 
9 
9 
Ambulatory Monitoring  
(48 hours minimum) 
 
 
 
 
9 
9 
9 
*  Women of child-bearing potential only 
†  Telephone call optional 
#  Optional procedure  
 
 
 

 
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Appendix 2. 
Investigator’s Responsibilities 
 
 

 
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The investigators have the following responsibilities: 
 
1. 
Subject Selection 
The investigator is responsible for assuring that all subjects entering the study conform to the 
subject selection criteria. 
 
2. 
Informed Consent 
The investigator is responsible for fully reviewing the nature of the study, the possible risks, and 
alternative treatments with the prospective subject prior to their enrollment in the study.  The 
investigator is responsible for obtaining written Informed Consent for each subject or his/her 
legal representative, prior to enrollment in the trial.  A copy of the signed Informed Consent 
Form will be maintained in the subject's medical record. 
 
3. 
Ethics Committee (EC) Approval 
The investigator must obtain approval for his participation in this protocol from the EC for the 
institution at which the procedure will be performed, prior to entering any subjects in the study.  
The Informed Consent document to be used will also be submitted by the Investigator to the EC 
for approval prior to initiation of the study.  Assurance that the EC approval of the study protocol 
and Informed Consent has been obtained will be provided to the Sponsor/Designee prior to 
initiation of the study. 
 
4.  
Subject Evaluations and Data Reporting 
The investigator, or trained designee, is responsible for performing the subject assessments as 
described in the study protocol.  Information generated by these evaluations will be recorded on 
the CRFs provided by the Sponsor/Designee or entered into the electronic data capture system 
(EDC) with access provided by the Sponsor/Designee.   
 
Following each subject visit, the CRFs will be completed in a timely manner, e.g., within 48 
hours.  Original reports from the subject assessments (source documents) will be retained as part 
of the subject’s study file. 
 
Investigator(s) will not deviate from the study protocol without prior approval of the 
Sponsor/Designee unless protection of the health, safety or welfare of study subjects requires 
prompt action. 
 
5. 
Record Retention 
In accordance with Commission Directive 2005/28/EC, the investigator shall retain the essential 
documents relating to a clinical trial for at least five years after its completion.   
 
The investigator shall retain the documents for a longer period, where so required by other 
applicable requirements or by an agreement between the Sponsor and the investigator.  
 
Essential documents shall be archived in a way that ensures that they are readily available, upon 
request, to the competent authorities.   
 

 
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The medical files of trial subjects shall be retained in accordance with national legislation and in 
accordance with the maximum period of time permitted by the hospital, institution or private 
practice. 
 
6. 
Investigational Material Accountability 
The investigator must maintain accurate records of the receipt of investigational material shipped 
by the Sponsor/Designee, including the date and lot numbers received.  In addition, accurate 
records must be kept on the amount and date that investigational material, by lot number, was 
used or returned for each subject in the trial.  The investigator must assure that study supplies be 
used only in subjects enrolled in the study and under the direct supervision of the investigator or 
co-investigators. 
 
Records of all investigational supplies received, used and returned must be kept by the principal 
investigator or his/her designee.  All unused investigational supplies will be returned to the 
Sponsor/Designee as soon as practical upon completion of enrollment.  Investigational material 
accounting procedures must be completed before the study is considered terminated. 
 
 

 
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Appendix 3. 
Sponsor’s Commitments 
 
 
 
 
 

 
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Affera, Inc. is committed to: 
 
1. 
Complying with the Declaration of Helsinki, and all applicable health authority regulations 
governing the conduct of clinical research studies. 
 
2. 
Protecting the rights, health, safety, and welfare of study subjects. 
 
3. 
Informing the clinical investigators of any new information about the study, which may 
affect the health, safety or welfare of the subjects, or may influence their decision to 
continue participation in the study. 
 
4. 
Providing the clinical investigators with the study protocol, and a full set of / access to 
CRFs on which to document the study evaluation variables for each subject entered into the 
study. 
 
5. 
Providing the statistical analysis and study report writing resources necessary to complete 
reporting of the study results. 
 
6. 
Ensuring equity of consideration among all investigators in multicenter studies in all 
matters of publications, meeting presentations, etc. 
 
7. 
Certifying that EC approval of the protocol and completion of the Investigator’s Agreement 
will occur prior to treatment at any investigational site.