Persistent AF (Asia Pacific) Observational Study
Conditions: Persistent Atrial Fibrillation
Sponsor: Abbott Medical Devices

Clinical Investigation Plan Cover Page 
87173 CIP Posting Cover Page Ver C 
Template 
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NCT Number: NCT04244396 
PerAF APAC
Persistent Atrial Fibrillation (Asia Pacific) Observational Study 
Study Document No: ABT-CIP-10295 
Version B 
Date: 29-JUN-2020 
Sponsor 
Abbott 
5050 Nathan Lane North 
Plymouth, MN 55442 
USA 

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
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SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
 
I have read and agree to adhere to the clinical investigation plan and all regulatory requirements 
applicable in conducting this clinical investigation. 
 
 
Site Principal Investigator: 
 
Printed name: 
Signature: 
Date: 
 
 
 

 
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Clinical Investigation Plan 
 
 
 
 
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TABLE OF CONTENTS 
 
1.0 
INTRODUCTION ........................................................................................................................... 8 
1.1 
Background and Rationale ......................................................................................................... 8 
 
Background ........................................................................................................................ 8 
 
Rationale for Conducting this Clinical Investigation ............................................................. 9 
2.0 
CLINICAL INVESTIGATION OVERVIEW .................................................................................... 10 
2.1 
Clinical Investigation Objective ................................................................................................ 10 
2.2 
Devices to be Used in the Clinical Investigation ....................................................................... 10 
 
Name of the Device Under Investigation ........................................................................... 10 
 
Indication for Use .............................................................................................................. 11 
 
Description of the Device Under Investigation ................................................................... 11 
2.2.3.1 
TactiCath Sensor Enabled Ablation Catheter ............................................................. 11 
 
Summary of Preclinical Studies ........................................................................................ 12 
 
Device Handling................................................................................................................ 13 
3.0 
CLINICAL INVESTIGATION DESIGN ......................................................................................... 13 
3.1 
Clinical Investigation Procedures and Follow-up Schedule ...................................................... 13 
3.2 
Measures Taken to Avoid and Minimize Bias ........................................................................... 14 
3.3 
Suspension or Early Termination of the Clinical Investigation .................................................. 15 
4.0 
ENDPOINTS ............................................................................................................................... 15 
 
Primary Safety Endpoint and Rationale ............................................................................ 15 
4.2 
Additional Data ........................................................................................................................ 16 
5.0 
SUBJECT SELECTION AND WITHDRAWAL ............................................................................. 17 
5.1 
Subject Population ................................................................................................................... 17 
5.2 
Subject Screening and Informed Consent ................................................................................ 17 
 
Subject Screening ............................................................................................................. 17 
 
Informed Consent ............................................................................................................. 18 
5.2.2.1 
Special Circumstances for Informed Consent ............................................................ 18 
5.3 
Eligibility Criteria ...................................................................................................................... 18 
 
General Eligibility Criteria .................................................................................................. 18 
 
Inclusion Criteria ............................................................................................................... 19 
 
Exclusion Criteria .............................................................................................................. 19 
5.4 
Subject Enrollment ................................................................................................................... 20 
5.5 
Subject Withdrawal .................................................................................................................. 21 
5.6 
Number of Subjects ................................................................................................................. 22 
5.7 
Total Expected Duration of the Clinical Investigation ............................................................... 22 

 
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6.0 
TREATMENT AND EVALUATION OF ENDPOINTS ................................................................... 22 
6.1 
Baseline Clinical Assessments ................................................................................................ 22 
6.2 
Peri-Procedural Considerations ............................................................................................... 23 
 
Anticoagulation ................................................................................................................. 23 
 
Antiarrhythmic Drug Therapy ............................................................................................ 23 
 
Vascular Access ............................................................................................................... 24 
 
Esophageal Temperature Monitoring ................................................................................ 24 
 
Pregnancy Testing ............................................................................................................ 24 
 
Thrombus Assessment ..................................................................................................... 24 
6.3 
Initial Ablation Procedure ......................................................................................................... 25 
 
Ablation Procedure ........................................................................................................... 25 
6.4 
Repeat Ablation Procedures .................................................................................................... 27 
6.5 
Pre-Discharge Visit (In-hospital) .............................................................................................. 27 
6.6 
Blanking and Therapy Consolidation Periods ........................................................................... 27 
6.7 
Follow-up Assessments ........................................................................................................... 28 
 
Unscheduled Visits ........................................................................................................... 29 
 
Patient Reported Outcome Measures – EQ-5D-5L Questionnaires................................... 30 
 
Schedule of Events ........................................................................................................... 30 
6.8 
Core Laboratory ....................................................................................................................... 31 
7.0 
Adverse Events ........................................................................................................................... 31 
7.1 
Adverse Event Definitions and Reporting ................................................................................. 32 
 
Adverse Event .................................................................................................................. 32 
7.1.1.1 
Adverse Event Reporting ........................................................................................... 32 
 
Serious Adverse Event (SAE) Reporting to Sponsor and IRB/EC ..................................... 32 
7.1.2.1 
SAE Reporting ........................................................................................................... 33 
 
Adverse Event Reporting to Country Regulatory Authorities by the Sponsor .................... 33 
 
Independent Adjudication of Adverse Events .................................................................... 33 
8.0 
STATISTICAL CONSIDERATIONS ............................................................................................. 33 
8.1 
Analysis Populations ................................................................................................................ 33 
8.2 
Statistical Analyses .................................................................................................................. 34 
 
Primary Safety Endpoint Analysis ..................................................................................... 34 
 
Additional Data Analyses .................................................................................................. 34 
8.3 
Sample Size Calculation and Assumptions .............................................................................. 35 
8.4 
Timing of Analysis .................................................................................................................... 35 
8.5 
Subgroup Analysis ................................................................................................................... 35 
8.6 
Multiplicity ................................................................................................................................ 35 

 
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8.7 
Procedures for Accounting for Missing Data ............................................................................ 35 
8.8 
Planned Interim Analysis ......................................................................................................... 35 
8.9 
Statistical Criteria for Termination ............................................................................................ 35 
8.10 
Success Criteria ....................................................................................................................... 35 
8.11 
Deviations from Statistical Plan ................................................................................................ 35 
9.0 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ............................................................... 35 
10.0 
QUALITY CONTROL AND QUALITY ASSURANCE ................................................................... 36 
10.1 
Selection of Clinical Sites and Investigators ............................................................................. 36 
10.2 
CIP Amendments ..................................................................................................................... 36 
10.3 
Training.................................................................................................................................... 36 
 
Site Training ..................................................................................................................... 36 
 
Training Required for the Use of the Device ..................................................................... 36 
10.4 
Monitoring ................................................................................................................................ 37 
10.5 
Deviations from CIP ................................................................................................................. 37 
10.6 
Quality Assurance Audit ........................................................................................................... 38 
10.7 
Committees ............................................................................................................................. 38 
 
Steering Committee .......................................................................................................... 38 
11.0 
DATA HANDLING AND RECORD KEEPING .............................................................................. 38 
11.1 
Protection of Personally Identifiable Information ...................................................................... 39 
11.2 
Data Management Plan ........................................................................................................... 39 
11.3 
Source Documentation ............................................................................................................ 39 
11.4 
Case Report Form Completion ................................................................................................ 40 
11.5 
Record Retention ..................................................................................................................... 40 
12.0 
ETHICAL CONSIDERATION....................................................................................................... 40 
12.1 
Institutional Review Board/Medical Ethics Committee Review and Approval ........................... 40 
13.0 
CLINICAL INVESTIGATION CONCLUSION ............................................................................... 41 
14.0 
PUBLICATION POLICY .............................................................................................................. 41 
15.0 
RISK ANALYSIS ......................................................................................................................... 41 
15.1 
Anticipated Clinical Benefits ..................................................................................................... 42 
15.2 
Foreseeable Adverse Events and Anticipated Adverse Device Effects .................................... 42 
15.3 
Residual Risks Associated with the Device Under Investigation, as Identified in the Risk 
Analysis Report .................................................................................................................................. 43 
15.4 
Risks Associated with Participation in this Clinical Investigation .............................................. 43 
15.5 
Possible Interactions with Protocol-Required Concomitant Medications................................... 44 
15.6 
Steps Taken to Control or Mitigate Risks ................................................................................. 44 
15.7 
Risk to Benefit Rationale .......................................................................................................... 44 

 
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16.0 
References .................................................................................................................................. 44 
 
 

 
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COMPLIANCE STATEMENT:  
 
This clinical investigation will be conducted in accordance with this Clinical Investigation Plan, the 
Declaration of Helsinki, applicable Good Clinical Practices and regulations (e.g., US 21 CFR Part 50, 21 
CFR Part 56, 21 CFR Part 812 and OUS ISO14155:2011) and the appropriate local legislation(s). The 
most stringent requirements, guidelines or regulations must always be followed. The conduct of the 
clinical investigation will be approved by the appropriate Institutional Review Board (IRB)/Ethics 
Committee (EC) of the respective investigational site and by the applicable regulatory authorities (e.g., 
FDA, PMDA, MHRA, etc.). 
 
 

 
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1.0 
INTRODUCTION 
This clinical investigation is intended to collect safety and effectiveness information for the TactiCath™ 
Contact Force Ablation Catheter, Sensor Enabled™ (TactiCath SE) for use in cardiac 
electrophysiological mapping and for the treatment of drug-refractory, recurrent symptomatic persistent 
atrial fibrillation (AF) when used in conjunction with a compatible radiofrequency (RF) generator and 
three-dimensional mapping system.  This clinical investigation will be a post-market observational study 
and is intended to generate additional clinical evidence for the TactiCath SE ablation catheter for the 
treatment of drug refractory, symptomatic persistent atrial fibrillation in the Asia Pacific (APAC) region. 
Approximately one hundred (100) subjects will be enrolled at up to 15 sites in South Korea, Singapore, 
Hong Kong, Taiwan, India, and other Asia Pacific countries as deemed necessary. This clinical 
investigation is sponsored by Abbott and will be conducted in accordance with this clinical investigation 
plan (CIP). All investigators involved in the conduct of the clinical investigation will be qualified by 
education, training, or experience to perform their tasks and this training will be documented 
appropriately. 
1.1 
Background and Rationale 
 Background 
Based on epidemiological studies of mainly North American and European populations, an estimated 
20.9 million men and 12.6 million women suffer from AF.1 The prevalence of AF is lower in Asians than in 
Westerners and is estimated to be approximately 0.7-1.1% in Asians older than 40. Despite this apparent 
difference in prevalence, the burden of AF in the Asia Pacific region is expected to become far greater 
than that in Western regions based on the increasing age and size of populations within the Asia Pacific 
regions.2,3 
AF is a result of multiple diseases and mechanisms that are not completely understood and will often 
exacerbate an underlying heart condition.  AF occurs when structural and/or electrophysiological 
abnormalities alter atrial tissue to promote abnormal impulse formation and/or propagation.4  Symptoms 
associated with AF include fatigue, palpitations, dyspnea, hypotension, syncope, and heart failure.  AF 
often progresses from paroxysmal to persistent over a variable period of time.  Patients with persistent 
AF have worse outcomes than for patients with paroxysmal AF and are more likely to develop potentially 
life-threatening problems, such as stroke, tachycardia-induced cardiomyopathy and congestive heart 
failure, all of which may increase mortality.5,6  Maintenance of sinus rhythm may confer a mortality benefit 
and is associated with improvements in symptoms and quality of life.   
 
Management of patients with AF has traditionally consisted of three main components: (1) 
anticoagulation for stroke prevention; (2) rate control; and (3) rhythm control.7 Persistent symptoms 
associated with AF remain the most compelling indication for a rhythm-control strategy.  The efficacy of 
radiofrequency catheter ablation for maintaining sinus rhythm is superior to current antiarrhythmic drug 
therapy in select patient populations.4  The decision whether to pursue catheter ablation depends on a 
large number of variables, including the type of AF, degree of symptoms, presence of structural heart 
disease, candidacy for alternative options such as rate control or antiarrhythmic drug therapy, likelihood 
of complications, and patient preference.4  Catheter ablation is considered a reasonable indication for 
patients with symptomatic persistent AF refractory or intolerant to at least one Class I or III antiarrhythmic 
medication.4,7  Catheter ablation may also be considered as first-line therapy in select patients before a 
trial of antiarrhythmic drug therapy when a rhythm-control strategy is desired.4,7 
 

 
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The method of catheter ablation for persistent AF remains controversial.5,7  The strategy for ablation is 
often individualized based on patient characteristics, atrial fibrillation history and coexisting structural 
heart disease. Electrical isolation of the pulmonary veins by catheter ablation is the cornerstone for most 
AF ablation procedures as most triggers for AF originate from the pulmonary veins.6  Pulmonary vein 
(PV) isolation involves creating circumferential lesions around the veins to electrically isolate them from 
the rest of the left atrium.  Additional non-PV ablation strategies are also often employed in patients with 
persistent AF to improve outcome and may consist of the following: ablation of the posterior wall of the 
left atrium; creating linear ablation lesions in the right or left atrium; mapping and ablation of areas of 
abnormal myocardial tissue; ablation of complex fractionated atrial electrograms or rotational activity; 
and/or ablation of autonomic ganglia.7  These additional non-pulmonary vein ablation strategies all have 
a Class IIb recommendation (benefit of AF ablation is greater or equal to the risks and AF ablation may 
be considered) based on a moderate quality of evidence for these approaches. 
 
Contact force sensing ablation catheter systems are a technology that is growing in adoption for AF 
ablation.  Contact force sensing catheter systems provide feedback to operators regarding the force 
applied by the catheter tip on the cardiac wall.  Recommendations for contact force catheters for atrial 
fibrillation ablation procedures are also defined in the 2017 HRS/EHRA/ECAS/APHRS/SOLAECE Expert 
Consensus on AF Ablation (Class IIa recommendation, Level of evidence C).7  
 
The TactiCath family of contact force sensing catheters have been studied extensively.  The earlier 
generation TactiCath catheters were investigated in the TOCCATA8, EFFICAS I9 and II10, and 
TOCCASTAR11 clinical trials.  The next generation, TactiCath Quartz, implemented an updated contact 
force sensing mechanism, which was studied in the TOCCASTAR Supplemental Clinical Study.  Long-
term follow up data are currently being collected in the TactiCath Quartz Post Approval Study.  These 
clinical trials have investigated the safety and effectiveness of the previous generations of the TactiCath 
ablation catheters for the treatment of drug refractory, symptomatic AF.8-11   
 
The TactiCath SE ablation catheter is the latest TactiCath contact force sensing catheter from Abbott, 
which incorporates a magnetic sensor for tracking with the EnSite Precision Mapping System and utilizes 
a new handle and shaft to improve catheter handling.  Preclinical testing has demonstrated that the 
TactiCath SE ablation catheter has an acceptable safety profile. Additionally, the ongoing TactiSense 
IDE trial evaluating the paroxysmal AF population currently being conducted in the United States, 
Europe, and Australia, as well as the Persist-End IDE trial evaluating the safety and effectiveness of this 
catheter in the persistent AF population that is being conducted in the United States and Australia, have 
demonstrated acceptable safety profiles as of the date of this document.   
 
The PerAF APAC trial is a prospective, single arm, non-randomized, observational, post-market clinical 
investigation to primarily evaluate the effectiveness of ablation with the TactiCath SE catheter for the 
treatment of drug refractory, symptomatic persistent AF in the Asia-Pacific population.  Additionally, the 
PerAF APAC study will be used as supplemental data to the Persist-End clinical trial being conducted in 
the United States and Australia. 
 Rationale for Conducting this Clinical Investigation 
The PERSIST-END investigational device exemption (IDE) clinical investigation currently being 
conducted by Abbott will be used to obtain regulatory approval from the Food and Drug Administration 
(FDA) for a persistent AF indication on the TactiCath™ catheter (TactiCath™ Contact Force Ablation 
Catheter, Sensor Enabled). Supplemental data obtained in the PerAF APAC trial will be used in 
conjunction with the Persist-End data to expand the paroxysmal AF indication to include a persistent AF 
indication in China and other Asia Pacific countries as needed.   

 
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Clinical Investigation Plan 
 
 
 
 
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 Indication for Use 
The indications for use for each country participating in this trial are listed below. 
Hong Kong, India, Singapore, and Thailand 
The TactiCath Contact Force Ablation Catheter, Sensor Enabled, is indicated for use in cardiac 
electrophysiological mapping (stimulation and recording), and, when used in conjunction with a 
radiofrequency generator, for cardiac ablation of supraventricular arrhythmias in the right and left atrium, 
including atrial fibrillation.  
 
Taiwan 
The TactiCath Contact Force Ablation Catheter, Sensor Enabled is indicated for use in cardiac 
electrophysiological mapping (including stimulation and recording) and for the treatment of left and right 
atrial, supraventricular arrhythmias, including atrial fibrillation during a cardiac ablation procedure when 
used in conjunction with a compatible radiofrequency generator. 
 
South Korea 
A device that is intended to measure the ECG, cardiac ejection, etc. and to transmit signals that are 
necessary for recording of these.  It is also used to deliver stimulation (pacing) and perform tissue 
ablation. 
 
Operating Principle: 
The TactiCath Contact Force Ablation Catheter, Sensor Enabled, is designed to facilitate 
electrophysiological mapping of the heart chambers and to transmit radiofrequency current to the 
catheter tip electrode for intracardiac purposes and when used in conjunction with a RF generator, for 
cardiac ablation of supraventricular arrhythmias in the right and left atrium, including atrial fibrillation.   
 Description of the Device Under Investigation 
2.2.3.1 TactiCath Sensor Enabled Ablation Catheter 
The TactiCath SE is designed to facilitate electrophysiological mapping of the heart chambers and to 
transmit RF current to the catheter tip electrode for intracardiac ablation purposes. The catheter is used 
in conjunction with a RF generator, an irrigation pump, and a dispersive pad (indifferent patch electrode) 
when ablating. TactiCath SE is compatible with introducers or sheaths with a minimum diameter of 8.5 F.  
TactiCath SE is a sterile, single use catheter with a 7.5 F shaft and an 8 F distal section. It is constructed 
of thermoplastic elastomer material and noble metal electrodes.  
 
TactiCath SE has novel contact force and magnetic sensors. It has a fluid lumen connected to open 
conduits within a 6-hole tip electrode for saline irrigation during the ablation procedure (Figure 1). For 
both uni-directional (Figure 2) and bi-directional catheters (Figure 3), the tip curvature is manipulated by 
the control mechanism located on the handle at the catheter's proximal end. To adjust the curve of the 
distal tip on the uni-directional catheter, the thumb control located on the handle may be pushed or 
pulled. To adjust the curve of the distal tip on the bi-directional catheter, the actuator may be used to 
deflect the catheter in either direction. The catheter interfaces with standard recording equipment and a 
compatible RF generator via the TactiSys Quartz Equipment using the optical connector and 19-pin 
electrical connector on the catheter. The catheters are available in eight distal curve shapes. 
 
Please refer to the IFU for additional information regarding the TactiCath SE device used in this clinical 
investigation. 
 

 
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Clinical Investigation Plan 
 
 
 
 
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Figure 1. Exposed View of the TactiCath SE Tip 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Figure 2. Uni-Directional TactiCath SE 
 
Figure 3. Bi-Directional TactiCath SE 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 Summary of Preclinical Studies 
Preclinical testing has demonstrated that the TactiCath SE ablation catheter has an acceptable safety 
profile. Abbott has performed several preclinical studies evaluating TactiCath SE. A perfused porcine thigh 
study demonstrated that the TactiCath SE catheter and the TactiCath Quartz catheter show no statistical 
difference in the lesions created or observed adverse event rates at IFU recommended ablation conditions. 
A subacute intracardiac study compliant with Good Laboratory Practice (GLP) and a chronic intracardiac 
 

 
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• 
PerAF APAC is a prospective clinical investigation in which the outcome is unknown at the time of 
enrollment 
• 
All subjects must meet the defined eligibility criteria to minimize selection bias  
• 
Guidance will be provided to sites regarding data collection for questionnaires   
• 
Case report forms for data collection will be provided to sites, which will minimize inter-observer 
variability.   
• 
Evaluation of the 6-month and 15-month Holter AF/AFL/AT recurrence data will be performed by 
an independent core laboratory.   
• 
Adverse events will be independently adjudicated by qualified physicians. 
3.3 
Suspension or Early Termination of the Clinical Investigation 
While no formal statistical rule for early termination of the clinical investigation for insufficient 
effectiveness of the device under investigation is defined, the Sponsor reserves the right to discontinue 
the clinical investigation at any stage or reduce the follow-up period with suitable written notice to the 
investigator. Possible reason(s) may include, but are not limited to: 
• 
A new unreasonable risk to the participating subjects has been identified such as an 
unanticipated increase in complaint rates related to the study.   
 
Should the clinical investigation be discontinued by the Sponsor, subjects will be followed per routine 
hospital practice with device-related AEs reported to the Sponsor as per vigilance/commercial reporting 
requirements. The investigator shall return all clinical investigation materials to the Sponsor and provide 
a written statement to the IRB/EC (if applicable). All applicable clinical investigation documents shall be 
subject to the same retention policy as detailed in Section 11.5.  
 
A Principal Investigator, IRB/EC or regulatory authority may suspend or prematurely terminate 
participation in the clinical investigation at the investigational site(s) for which they are responsible. The 
investigators will follow the requirements specified in the Clinical Trial Agreement.  
 
If the Sponsor suspends or prematurely terminates the clinical investigation at an individual site in the 
interest of safety, the Sponsor will inform all other Principal Investigators. 
 
If suspension or premature termination occurs, the Principal Investigator or authorized designee will 
promptly inform the enrolled subjects at his/her site, if appropriate, and return patients to their standard 
medical treatment. 
4.0 
ENDPOINTS 
Only non-powered endpoints will be assessed in this trial. 
 Primary Safety Endpoint and Rationale 
The rate of device and/or procedure-related serious adverse events with onset within 7-days of any 
ablation procedure that uses the TactiCath SE catheter (initial or repeat procedure performed ≤180 days 
of initial procedure) that are defined below: 
 
• 
Atrioesophageal fistula1 
• 
Cardiac tamponade/perforation1 

 
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 Informed Consent 
The Investigator or his/her authorized designee (if applicable) will conduct the Informed Consent 
process, as required by applicable regulations and the center’s IRB/EC. This process will include a 
verbal discussion with the subject on all aspects of the clinical investigation that are relevant to the 
subject’s decision to participate, such as details of clinical investigation procedures, anticipated benefits, 
and potential risks of clinical investigation participation. Subjects must be informed about their right to 
withdraw from the clinical investigation at any time and for any reason without sanction, penalty or loss of 
benefits to which the subject is otherwise entitled. Withdrawal from the clinical investigation will not 
jeopardize their future medical care or relationship with the investigator.  
 
During the discussion, the Principal Investigator or his/her authorized designee will avoid any improper 
influence on the subject and will respect subject’s legal rights. Financial incentives will not be given to the 
subject. Subjects may be compensated for time and travel directly related to the participation in the 
clinical investigation. The subject shall be provided with the Informed Consent form separately that is 
written in a language that is understandable to the subject and has been approved by the center’s 
IRB/EC. The subject shall have adequate time to review, ask questions, and consider participation. The 
Principal Investigator or his/her authorized designee will make efforts to ensure that the subject 
understands the information provided. If the subject agrees to participate, the Informed Consent form 
must be signed and dated by the subject and thereafter by the person obtaining the consent prior to any 
clinical investigation-specific procedures. The signed original will be filed in the subject’s hospital or 
research charts, and a copy will be provided to the subject. 
 
Failure to obtain informed consent from a subject prior to clinical investigation enrollment should be 
reported to Sponsor within 5 working days and to the reviewing center’s IRB/EC according to the IRB’s/ 
EC’s reporting requirements. 
 
If, during the clinical investigation, new information becomes available that can significantly affect a 
subject's future health and medical care, the Principal Investigator or his/her authorized designee (if 
applicable) will provide this information to the subject. If relevant, the subject will be asked to confirm 
their continuing informed consent in writing. 
5.2.2.1 Special Circumstances for Informed Consent  
The following individual populations will be excluded from participation in this clinical investigation: 
• 
Incapacitated individuals, defined as persons who are mentally ill, mentally handicapped, or 
individuals without legal authority, are excluded from the study population. 
• 
Individuals under the age of 18 or age of legal consent are excluded from the study population. 
• 
Individuals unable to read or write are excluded from the study population. 
• 
Pregnant or breastfeeding women are excluded from the study population. 
 
All other aspects of the Informed Consent process should be in compliance with Section 5.2.2. 
5.3 
Eligibility Criteria 
 General Eligibility Criteria 
Assessment of eligibility criteria is based on review of candidate medical records at the site, an interview 
with a candidate patient, and determination by the investigator. If the specific tests noted in Section 5.2.1 
(LVEF, LA diameter, and presence of thrombus) were not completed prior to obtaining consent, they 

 
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must be assessed before the subject has an ablation catheter inserted into their vasculature for an 
ablation procedure. 
Patients must meet ALL of the inclusion criteria to be considered for this clinical investigation. If ANY of 
the exclusion criteria are met, the patient is excluded from the clinical investigation.   
 Inclusion Criteria 
1) 
Patient must provide written informed consent prior to any clinical investigation related 
procedure. 
2) 
Documented symptomatic persistent AF, which is defined as continuous AF sustained 
beyond 7-days and less than 1-year that is documented by (1) a physician's note AND (2) a 
24-hour Holter within 90-days prior to the procedure, showing continuous AF, OR (3) two 
electrocardiograms (from any form of rhythm monitoring) showing continuous AF, with 
electrocardiograms taken at least 7 days apart 
3) 
Refractory or intolerant to at least one Class I or III antiarrhythmic drug (AAD) as evidenced 
by recurrent symptomatic AF 
Note:  Intolerance is defined as unable, unwilling, or refusal to take Class I or III AADs. 
4) 
Age 18 years or older 
5) 
Able and willing to comply with all pre-, post-, and follow-up testing and requirements 
 Exclusion Criteria 
1) 
Continuous AF > 12 months (longstanding persistent AF) 
2) 
Previous left atrial surgical or catheter ablation for atrial fibrillation or a previous procedure 
that required an incision in the left atrium with resulting scar 
3) 
Any cardiac procedure (surgical or percutaneous) within 90-days prior to the initial 
procedure  
NOTE: Diagnostic cardiac procedures in which no intervention, implant, or incision was 
made in the cardiac tissue are not considered a surgical or percutaneous cardiac 
procedure. 
4) 
CABG surgery within the 6-months (180-days) prior to the initial procedure 
5) 
Valvular cardiac surgical/percutaneous procedure (i.e. ventriculotomy, valve repair or 
replacement and/or presence of a prosthetic or mechanical valve) 
6) 
Any carotid stenting or endarterectomy 
7) 
Documented or known left atrial thrombus on imaging  
8) 
Left atrial (LA) diameter > 50 mm (parasternal long axis view or by CT) 
9) 
Left ventricular ejection fraction (LVEF) < 40% 
10) Unable to take anticoagulation medication due to contraindication or intolerance  
11) History of blood clotting or bleeding abnormalities 
12) Myocardial infarction (MI), acute coronary syndrome, percutaneous coronary intervention 
(PCI) within the 3-months (90-days) prior to the initial procedure 
13) Documented thromboembolic event (including TIA) within the 12-months (365 days) prior to 
the initial procedure 
14) Rheumatic heart disease 
15) Uncontrolled heart failure or NYHA functional class III or IV 

 
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16) Severe mitral regurgitation (regurgitant volume ≥ 60 mL/beat, regurgitant fraction ≥ 50%, 
and/or effective regurgitant orifice area ≥ 0.40cm2) 
17) Awaiting cardiac transplantation or other cardiac surgery within the 12-months (365 days) 
following the initial ablation procedure 
18) Unstable angina at the time of the initial procedure 
19) Acute illness or active systemic infection or sepsis 
20) AF secondary to electrolyte imbalance, thyroid disease, acute alcohol intoxication, major 
surgical procedure in the preceding 3-months, or other reversible or non-cardiac cause 
21) Diagnosed atrial myxoma 
22) Presence of implanted implantable cardioverter defibrillator (ICD) or cardiac 
resynchronization therapy-defibrillator (CRT-D) 
23) Significant pulmonary disease, (e.g., restrictive pulmonary disease, constrictive or chronic 
obstructive pulmonary disease) or any other disease or malfunction of the lungs or 
respiratory system that produces chronic symptoms 
24) Significant congenital anomaly or other anatomic or comorbid medical problem that in the 
opinion of the investigator would preclude enrollment in this study or compliance with the 
follow-up requirements or impact the scientific soundness of the clinical trial results  
25) Pregnant or nursing subjects and those who plan pregnancy during the clinical investigation 
follow-up period 
26) Enrollment in an investigational study evaluating another device, biologic, or drug that may 
interfere with this clinical investigation at the time of the initial procedure or within 30 days 
prior to the initial procedure 
27) Presence of any condition that precludes appropriate vascular access or manipulation of 
catheter 
28) Life expectancy less than 12-months 
29) Body mass index > 40 kg/m2 
30) Known sensitivity to contrast media (if needed during the procedure) that cannot be 
controlled with pre-medication 
31) Renal failure requiring dialysis 
32) Presence of other medical, social, or psychological conditions that, in the investigator’s 
opinion, could limit the subject’s ability to participate in the clinical investigation or to comply 
with follow-up requirements, or impact the scientific soundness of the clinical investigation 
results 
33) History of atriotomy or ventriotomy 
34) Implanted endocardial left atrial appendage occlusion device 
5.4 
Subject Enrollment 
A patient is considered enrolled in the clinical investigation from the moment the patient provides written 
informed consent and meets all eligibility criteria.  
 
If a TactiCath SE device is used for ablation on an enrolled subject who does not meet eligibility criteria 
for the trial, they will not be withdrawn from the trial, will be counted in the analysis population and will 
complete all follow-up requirements. 

 
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5.5 
Subject Withdrawal 
Each enrolled subject shall remain in the clinical investigation until completion of the required follow-up 
period.  However, a subject’s participation in any clinical investigation is voluntary and the subject has 
the right to withdraw at any time without penalty or loss of benefit. Conceivable reasons for 
discontinuation may include, but not be limited to, the following: 
• 
Death 
• 
Voluntary withdrawal 
• 
Lost to follow-up (described below) 
• 
Subject’s following is terminated according to Section 3.3 
The Sponsor must be notified of the reason(s) for subject discontinuation. The site will provide this 
information to the Sponsor as documented on the appropriate CRF. Investigators must also report this to 
their respective IRB/EC as defined by their institution’s procedure(s).  
 
No additional follow–up will be required or data recorded from subjects once they are withdrawn from the 
clinical investigation, except for the status (deceased/alive).  If a subject withdraws from the investigation 
due to problems related to the safety or performance of the device under investigation, they will be 
followed by their regular physician per their standard of care.  
 
If for any reason, the subject has the TactiCath SE inserted into their vasculature, but no ablation was 
performed, and the subject will not be rescheduled to receive another ablation procedure, the subject will 
be followed for 30-days to assess safety and then exited from the trial.  
 
In the event that a subject does elect to withdraw from the trial, the site should make attempts to 
schedule the subject for a final visit. At this final follow-up visit, the subject will undergo assessments as 
outlined for an unscheduled visit (Section 6.7.1) if the visit does not coincide with a scheduled follow-up 
visit. 
 
Withdrawn subjects count towards the total enrollment at the site and will not be replaced by enrolling 
additional subjects. 
 
Lost-to-Follow-up 
 
If the subject misses two consecutive scheduled follow-up time points and the attempts at contacting the 
subject detailed below are unsuccessful, then the subject is considered lost-to-follow-up. Site personnel 
shall make all reasonable efforts to locate and communicate with the subject (and document these efforts 
in the source documents), including the following, for each time an attempt was made to contact the 
subject: 
• 
A minimum of two telephone calls on different days over the specified follow-up windows to 
contact the subject should be recorded in the source documentation, including date, time and 
initials of site personnel trying to make contact. 
• 
If these attempts are unsuccessful, a letter should be sent via registered mail to the subject. 
• 
If a subject misses one or more non-consecutive follow-up contact time points, it will be 
considered a missed visit. The subject may then return for subsequent visits.  
• 
If the subject misses two consecutive time points and the above-mentioned attempts at 
communicating with the subject are unsuccessful, the subject will be considered lost-to-follow-up.  

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 23 of 53 
• 
Thrombus assessment must be performed as specified in Section 6.2.6. 
• 
Administration of the EuroQol Five Dimensions Questionnaire (EQ-5D-5L) quality of life 
questionnaire as defined in Section 6.7.1 
• 
Documentation of adverse events and protocol deviations that occur after consent and prior to the 
procedure 
6.2 
Peri-Procedural Considerations 
 Anticoagulation 
The anticoagulation strategies from the 2017 Expert Consensus Statement on Catheter and Surgical 
Ablation for AF7 for pre- and post-ablation are outlined below and are recommended to be followed for 
management of study subjects.  However, it is strongly recommended that a strategy of 
uninterrupted anti-coagulation be in place for peri-operative management.  All start and stop times 
of anticoagulants must be documented for the trial.  Subjects who are taking coumadin or warfarin will 
have international normalized ratio (INR) values documented on the day of the procedure and after the 
drug is restarted after the ablation procedure. 
Pre-ablation 
• 
Patients who are therapeutically anticoagulated with warfarin, dabigatran or rivaroxaban prior to 
the ablation are recommended to have the ablation procedure performed without interruption of 
the anticoagulant. 
 
• 
Patients anticoagulated with a novel oral anticoagulant (NOAC) prior to undergoing an AF 
ablation procedure may have one to two doses of the NOAC withheld prior to AF ablation with re-
initiation of the NOAC post-ablation. 
 
• 
Anticoagulation guidelines that pertain to cardioversion of AF should be adhered to in patients 
who present for an AF ablation procedure. 
 
Post-ablation 
• 
In patients who are not therapeutically anticoagulated prior to catheter ablation of AF and in 
whom warfarin will be used for anticoagulation post-ablation, low molecular weight heparin or 
intravenous heparin should be used as a bridge for initiation of systemic anticoagulation with 
warfarin following AF ablation. 
 
• 
Systemic anticoagulation with warfarin or NOAC is recommended for at least 2-months post-
ablation of AF.  Systemic anticoagulation beyond 2-months post-ablation should be based on the 
patient’s stroke risk profile (not on the perceived success or failure of the ablation procedure). 
 
• 
In patients who have not been anticoagulated prior to catheter ablation of AF or in whom 
anticoagulation with a NOAC or warfarin has been interrupted prior to ablation, administration of a 
NOAC 3 to 5 hours after achievement of hemostasis is reasonable post-ablation. 
 Antiarrhythmic Drug Therapy 
The 2017 Consensus Statement on Catheter and Surgical Ablation for Atrial Fibrillation7 states that 
AADs need to be discontinued for at least five half-lives and beta-blockers withheld for at least 24-hours 
prior to the ablation procedure if a strategy searching for non-pulmonary vein triggers is employed.  As 

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 24 of 53 
the ablation strategy is left to the discretion of the investigator, other than the requirement for PV 
isolation, this clinical investigation will not require that all subjects discontinue Class I and III AADs for at 
least five half-lives.  However, AAD usage (start and stop date, time, frequency and dose information) will 
be documented for the trial prior to and after the subject’s procedure(s). 
 
During the blanking period after the ablation procedure, it is recommended that any current AAD 
medication be continued following the ablation procedure to aid with healing. Current AADs should be 
withdrawn 4-6 weeks after ablation, unless clinically contraindicated, to assess for recurrence of 
symptoms and for determination of the need for a repeat ablation during the blanking or therapy 
consolidation periods.  It is recommended that sites phone subjects 4-6 weeks after ablation to remind 
them to discontinue their AAD medication. 
 
It is recommended that subjects be taken off all Class I and III AADs prescribed for AF/AFL/AT after the 
blanking and therapy consolidation periods.  If the investigator feels that the subject may benefit from a 
Class I or III AAD during the 9-month evaluation period (post-blanking and therapy consolidation 
periods), then the investigator should first prescribe a previously ineffective Class I or III AAD up to the 
historic maximum ineffective dose prior to the ablation procedure.  If the historic maximum ineffective 
dose remains ineffective then a new Class I or III AAD may be initiated.     
 Vascular Access 
It is strongly recommended that vascular access be obtained using ultrasound to minimize complications. 
 Esophageal Temperature Monitoring 
It is strongly recommended that esophageal temperature be monitored using an esophageal temperature 
probe at the anatomical location nearest the site of energy delivery.  Alternatively, esophageal deviation 
may be performed when ablating near the esophagus. 
Termination of energy is strongly recommended if a >1°C rise in esophageal temperature is observed.  
 Pregnancy Testing 
A urine pregnancy test must be performed for women of child-bearing potential, preferably on the day of 
the procedure. 
 Thrombus Assessment 
Left atrial thrombus assessment by transesophageal echocardiography (TEE) or phased-array 
intracardiac echocardiography (ICE) must be performed within one day of the ablation procedure or on 
the day of the procedure.   
 
If a thrombus is discovered within a day of the procedure, the procedure should be postponed, and the 
subject placed on anticoagulation until the thrombus is resolved and confirmed by imaging. Once 
confirmation is obtained demonstrating resolution of the thrombus, the inclusion/exclusion criteria should 
be re-reviewed for the subject to confirm continued eligibility for the trial.   
 
The subject will not need to be re-consented for the trial after the thrombus resolves, provided that the 
subject meets all eligibility criteria and will undergo an ablation procedure within 90-days of the original 
consent date unless otherwise indicated by the governing IRB/EC.  

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 25 of 53 
6.3 
Initial Ablation Procedure 
 Ablation Procedure 
For those subjects meeting eligibility criteria and who are enrolled in the trial, it is preferable that the 
ablation procedure be performed within 14-days of consent.  Any subject who does not meet eligibility 
requirements will be a screen failure and will be excluded from this trial. 
The subject’s rhythm when they enter the EP lab will be documented for the trial.  All cardioversions that 
occur from the time the subject enters the lab to the start of the procedure and during the procedure will 
be documented.  
It is recommended that heparin be administered prior to trans-septal puncture during the AF catheter 
ablation procedure and adjusted to achieve and maintain an ACT of at least 300 seconds.  Use of an ICE 
probe during the procedure to guide septal puncture and to monitor catheter position and manipulation is 
strongly recommended.  Administration of protamine to reverse heparin is acceptable. 
Following trans-septal access, a standard treatment scheme for mapping and ablation should be 
conducted.  Use of robotic systems or Stereotaxis to assist with the procedure is not allowed.  Physicians 
performing ablations must be qualified operators and trained on the study.  Each physician who ablates 
during a particular case needs to be documented on the Procedure CRF.   
The procedure should be performed according to the TactiCath SE Instructions for Use document using 
the recommended ablation parameters as noted in the document: 
• 
Power (10 - 30W) 
• 
Contact force (target 20 g, 10-30 g) 
• 
Temperature (37 – 50 °C) 
• 
Irrigation flow rate (17 - 30 ml/min) 
 
When ablating near the left atrial posterior wall, it is recommended that a minimum targeted contact force 
of 5-10 grams be used as specified in the 2017 HRS Consensus Statement.7  Recommended maximum 
parameters for ablating the left atrial posterior wall near the esophagus are: 
• 
Contact force: ≤15 g for ≤10 seconds 
• 
Power: up to 40W 
 
The ablation strategy outlined in Figure 5 is recommended for initial ablation of all subjects: 
1. Perform wide area circumferential ablation to electrically isolate the pulmonary veins. 
2. Administer isoproterenol following initial pulmonary vein isolation if the subject is in sinus rhythm to 
identify gaps in ablation and to identify and ablate any additional AF triggers. 
3. Cardiovert the subject before isoproterenol challenge if he/she is not in sinus rhythm after initial 
pulmonary vein isolation. 
4. Ablation of additional cardiac substrate (e.g. ablation of complex fractionated atrial electrograms 
(CFAE) or linear ablations) should only be considered if sinus rhythm is not restored after isolation 
of the pulmonary veins and ablation of non-PV triggers. 
 
 
 
 

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 26 of 53 
Figure 5. Persistent Atrial Fibrillation Ablation Strategy 
 
 
 
All subjects will receive ablations to achieve electrical isolation of the PVs. A minimum 20-minute wait 
period following electrical isolation of all PVs with assessment and documentation of entrance block is 
recommended per the 2017 Consensus Statement.7  It is also recommended in the 2017 Consensus 
Statement that exit block also be demonstrated.   
 
If PV reconnection occurs during or after the wait period following initial PV isolation of all veins, the 
vein(s) that reconnected and whether it was successfully isolated after administration of additional 
ablation lesions will be documented on the CRF.  Another wait period is not required after performing 
touch-up ablation lesions for reconnected PVs.   
 
Subjects with a history of AFL, AT or other SVT (spontaneous or induced) or if these arrhythmias are 
induced at the time of AF ablation, should undergo additional targeted ablation as clinically indicated.  All 
subjects with a history of typical atrial flutter or induced cavotricuspid isthmus (CTI)-dependent atrial 
flutter need to undergo concomitant AFL ablation and are recommended to have bi-directional block 
verified by mapping and pacing maneuvers after initial bi-directional block is achieved.   
 
Additional non-PV AF ablation targets (e.g. linear ablation, elimination of CFAEs, rotational activity, 
autonomic ganglia, isolation of the left atrial appendage, ablation of scar identified by voltage mapping or 
MRI, and non-PV triggers) are permitted per the investigator’s discretion and will be documented for the 
trial if sinus rhythm is not restored after isolation of the PVs and ablation of non-PV triggers.  If a linear 
ablation strategy is used, documentation of bidirectional block across the ablation line should be 
demonstrated and assessed in sinus rhythm and with differential pacing maneuvers.  High-dose 
isoproterenol may be administered to screen for and ablate non-PV triggers.  If CFAEs, rotational activity, 
or non-PV triggers are ablated, the acute goal is elimination of CFAEs, rotational activity, and non-PV 
triggers and AF termination.  
 

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 27 of 53 
The goal is that the subject is in sinus rhythm at the end of the procedure.  If AF cannot be terminated by 
ablation at the conclusion of the procedure, it is recommended that the patient be cardioverted and PV 
isolation rechecked.  
 
It is required to verify that the subject has not experienced pericardial effusion at the end of the procedure. 
 
If for any reason, the subject has the TactiCath SE inserted into their vasculature, but no ablation is 
performed and the subject will not be rescheduled to receive another ablation procedure, the subject will 
be followed for 30-days to assess safety and then exited from the trial.  Follow-up at 30-days will be 
conducted via a phone call to the subject (may also be an on-site visit).  Subjects who will have their 
ablation procedure re-scheduled will not need to be re-consented for the trial provided they are rescreened 
(all eligibility criteria met prior to the procedure) within 90-days of the initial consent date.   
6.4 
Repeat Ablation Procedures 
One ablation procedure for treatment of AF/AT/atypical AFL recurrence is allowed during the blanking 
and therapy consolidation periods (within 180 days post-initial procedure) using the recommended 
parameters listed in the TactiCath SE Instructions for Use document.  Note that recurrence and ablation 
of typical AFL alone does not count as a repeat procedure for AF recurrence. 
 
Certain assessments need to be performed if a repeat ablation is required. Thrombus assessment must 
be performed prior to ablating the subject.  Verification of the exclusion of pericardial effusion must also 
be performed prior to the conclusion of the procedure. 
 
A 7-day (± 2 days) follow-up phone call or in-person visit to the subject will be conducted after the repeat 
procedure.  All other follow-up visits will occur as previously scheduled from the initial ablation procedure.  
Note that the 90-day blanking period followed by a 90-day therapy consolidation period are still in place 
from the initial procedure.    
6.5 
Pre-Discharge Visit (In-hospital) 
Same day discharge after the ablation procedure is not recommended for the study, even if it is considered 
standard of care at some institutions.  Active surveillance of the subject’s postoperative care and condition 
is recommended for at least 72-hours or prior to discharge, whichever occurs first. 
The following are required testing for the Pre-Discharge Visit: 
• 
Complete physical exam and 12-lead ECG 
• 
Neurological assessment as recommended in the 2017 Consensus Statement7 
• 
Document AAD and anticoagulant drug usage 
• 
Document adverse events and protocol deviations 
If the subject requires an extended hospitalization due to a complication or other reason, all pre-discharge 
testing should be performed prior to discharge, but no later than 72 hours post-procedure.   
6.6 
Blanking and Therapy Consolidation Periods 
A blanking period of 90-days will be employed after the initial ablation procedure, followed by a 90-day 
therapy consolidation period and then a 9-month evaluation period for a total of 15-months of follow-up.  

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 28 of 53 
Early recurrence of AF, AFL, or AT within the blanking period or therapy consolidation period will not be 
considered treatment failures.  During the blanking and therapy consolidation periods, adjustment of 
antiarrhythmic medications, cardioversions, and one repeat ablation procedure may be performed. 
6.7 
Follow-up Assessments  
Subjects will undergo the following assessments described below at 7-14 days and at 3, 6, 12 and 15-
months post-ablation. 
 
7-14 Day Follow-up Visit  
This visit constitutes a phone call to the subject after each ablation procedure (initial and if applicable, a 
repeat procedure).  This visit may also be conducted in-person at the site.  Documentation for the trial 
consists of the following: 
• 
Document AAD and anticoagulant drug usage 
• 
Document adverse events and protocol deviations   
 
3-Month (91 + 21 days) Follow-Up Visit 
The 3-month follow-up visit is a scheduled in-person site visit.  When subjects are seen at the 3-month 
visit, it is recommended that they are weaned off AADs during the therapy consolidation period if they are 
doing well and have not discontinued these medications prior to this visit. 
• 
Perform 12-lead ECG 
• 
Document AAD and anticoagulant usage  
• 
Administer the EQ-5D-5L questionnaire as defined in Section 6.7.2 
• 
Document adverse events and protocol deviations 
• 
It is recommended to provide the subject with an event monitor for recording at regular intervals 
(e.g. monthly) and/or for symptomatic events through the 15-month visit. 
• 
It is recommended that a 24-hour Holter be performed 
• 
After the 3-month visit through the end of the study, any signs or symptoms of AF/AFL/AT 
recurrence should be recorded, and the subject should have either a 12-lead ECG or other form 
of ECG monitoring per the site’s standard practice to determine if recurrence has occurred. 
 
6-Month (181 + 30 days) Follow-Up Visit 
The 6-month follow-up visit is an in-person site visit. 
• 
Perform 12-lead ECG 
• 
Document AAD and anticoagulant usage  
• 
Administer the EQ-5D-5L questionnaire as defined in Section 6.7.2 
• 
Document adverse events and protocol deviations 
• 
If there are symptoms of AF/AFL/AT present, the subject should have either a 12-lead ECG or 
other form of ECG monitoring to document the  AF/AFL/AT recurrence  

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 29 of 53 
• 
 Administer a 24-hour Holter monitor provided by the core laboratory (required)Document any 
recurrences including details of any repeat electrophysiology studies 
 
12-Month (365 ± 30 days) Follow-Up Visit 
The 12-month follow-up visit is an in-person site visit. 
• 
Perform 12-lead ECG 
• 
Document AAD and anticoagulant usage  
• 
Administer the EQ-5D-5L questionnaire as defined in Section 6.7.2 
• 
Document adverse events and protocol deviations 
• 
If there are symptoms of AF/AFL/AT present, the subject should have either a 12-lead ECG or 
other form of ECG monitoring to document the AF/AFL/AT recurrence 
• 
It is recommended that a 24-hour Holter be performed 
• 
Document any recurrences including details of any repeat electrophysiology studies 
 
15-Month (450 ± 30 days) Follow-Up Visit 
The 15-month follow-up visit is a scheduled in-person site visit. 
• 
Perform 12-lead ECG 
• 
Document AAD and anticoagulant usage  
• 
Administer the EQ-5D-5L questionnaire as defined in Section 6.7.2 
• 
Document adverse events and protocol deviations 
• 
If there are symptoms of AF/AFL/AT present, the subject should have either a 12-lead ECG or 
other form of ECG monitoring to document the AF/AFL/AT recurrence  
• 
Document any recurrences including details of any repeat electrophysiology studies 
• 
Administer a 24-hour Holter monitor provided by the core laboratory (required) 
 Unscheduled Visits 
If a subject is seen by any physician for possible AF recurrence and/or arrhythmia associated symptoms 
outside of a regularly scheduled study visit and/or had an urgent care or emergency room visit regarding 
possible arrhythmia recurrence, these visits need to be documented as “Unscheduled Visits”, unless the 
visit is already documented on an Adverse Event CRF.  If there is an Adverse Event associated with this 
visit, then an Unscheduled Visit CRF does not need to be completed.   
 
Minimally, the following information should be documented for an unscheduled visit.   
• 
12-lead ECG, if performed during the visit 
• 
Document AAD and anticoagulant usage  
• 
Document adverse events and protocol deviations    

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 30 of 53 
 Patient Reported Outcome Measures – EQ-5D-5L Questionnaires 
The coordinator or designee will administer patient-reported outcome questionnaires. It is important the 
subject understands the meaning of all words and instructions in the questionnaires. The subject should 
be instructed to ask any questions about the questionnaires if further explanation is needed. Once the 
questionnaires are completed, the coordinator or designee will review for completeness to verify that all 
questions have been answered according to the directions provided. 
The EuroQol Five Dimensions Questionnaire (EQ-5D-5L) patient-reported outcome measure will be 
collected for this trial. The EQ-5D-5L questionnaire is a standardized measure of health status that is 
applicable to a wide range of health conditions and treatments.  It provides a simple descriptive profile 
and a single index value for health status that can be used in the clinical and economic evaluation of 
health as well as in population health surveys.  EQ-5D-5L is designed for self-completion and is ideally 
suited for use in postal surveys, in clinics, and in face-to-face interviews and takes only a few minutes to 
complete.   The questionnaire includes five dimensions assessing mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression.  Each dimension is measured based on responses to 5 levels: 
no problems, slight problems, moderate problems, severe problems, and extreme problems.  
Respondents evaluate their overall health status using a visual analogue scale, which can easily be 
converted to quality-adjusted life years for cost utility analysis.   
 
Note that it will not be a deviation for the EQ-5D-5L questionnaire be administered by phone.  Research 
personnel should use the EQ-5D-5L Script for Telephone Interview questionnaire for visits conducted 
over the phone.   
 Schedule of Events 
The schedule of activities specific to this clinical investigation are described in the preceding sections 
and are summarized in Table 2. 
Table 2. Schedule of PerAF APAC Clinical Investigation Activities 
Activity 
Enrollment
/ Baseline 
Procedure 
(~14-days 
of consent) 
Pre-
Discharge 
(<72 hrs 
post-proc.) 
7-14 Day  
Phone Call 
or In-Person 
(7-14 days) 
3-Month 
In-Person 
(91+21 days) 
6-Month 
In-Person  
(181+30 days) 
12-Month 
In-Person 
(365±30 days) 
15-Month 
In-Person 
(450±30 days) 
Informed Consent  
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Cardiovascular 
History 
X 
 
 
 
 
 
 
 
AAD & Anticoagulant 
Medications 
X 
 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
 
X 
 
 
 
 
 
Neurological Exam 
X1 
 
X1 
 
 
 
 
 
NYHA 
X 
 
 
 
 
 
 
 
CHA2DS2VASc score 
X 
 
 
 
 
 
 
 
12-Lead ECG 
X2 
 
X 
 
X 
X 
X 
X 
EQ-5D-5L 
Questionnaire 
X 
 
 
 
X 
X 
X 
X 
24-Hour Holter 
X2 
 
 
 
X5 
X5 
X5 
X5 
Urine Pregnancy Test 
 
(X) 
 
 
 
 
 
 
Confirm absence of 
thrombus 
 
X3 
 
 
 
 
 
 

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 31 of 53 
Activity 
Enrollment
/ Baseline 
Procedure 
(~14-days 
of consent) 
Pre-
Discharge 
(<72 hrs 
post-proc.) 
7-14 Day  
Phone Call 
or In-Person 
(7-14 days) 
3-Month 
In-Person 
(91+21 days) 
6-Month 
In-Person  
(181+30 days) 
12-Month 
In-Person 
(365±30 days) 
15-Month 
In-Person 
(450±30 days) 
Ablation procedure 
 
X 
 
 
 
 
 
 
Assess for Pericardial 
Effusion 
 
X4 
 
 
 
 
 
 
Monthly Event 
Recording 
 
 
 
 
X6 
X6 
X6 
X6 
Adverse Event 
Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
Document Deviations 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
Withdrawal 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) If applicable 
1.  A neurological assessment is recommended to be performed as outlined in the 2017 Consensus Statement. 
2.  Either a 24-hr Holter or 2 ECGs obtained ≥7 days apart may be used to demonstrate continuous AF at Baseline. 
3.  Thrombus assessment must be performed the day prior to or on the day of the procedure.  If a thrombus is discovered, the 
procedure should be postponed and the subject placed on anticoagulation until the thrombus is resolved as confirmed by 
imaging.  
4.  Imaging must be performed prior to the conclusion of the procedure to exclude pericardial effusion. 
5.  24-hour Holters must be obtained at the 6-month and 15-month follow-up visits.  It is recommended that a 24-hour Holter be 
obtained at the 3-month and 12-month follow-up visits. 
6.  It is recommended that event recordings are collected monthly after the initial ablation procedure and whenever the subject is 
experiencing a symptomatic episode starting at 3-months to 15-months post-procedure as noted in the 2017 Consensus 
Statement. 
6.8 
Core Laboratory 
A core lab will be used for the collection, interpretation, and collation of data obtained from the following 
sources: 
 
• 
24-hour Holter monitoring at the 6-month and 15-month follow-up visits 
 
The core lab will provide independent review of this data by appropriately trained personnel using 
standardized procedures to interpret Holter tracings for adjudication of atrial arrhythmias.  Findings will 
be communicated to the investigator and to the Sponsor.  The core lab’s adjudication findings will be 
used for analysis. 
7.0 
Adverse Events 
To comply with worldwide standards and guidelines on clinical investigation adverse event reporting, the 
Sponsor has adopted uniform and worldwide applicable standard definitions and reporting timelines to be 
used and adhered to by the investigators.  
 
Determination of whether there is a reasonable possibility that the device under investigation caused or 
contributed to an AE is to be determined by the Investigator and recorded on the appropriate CRF 
form. Determination should be based on assessment of temporal relationships, evidence of alternative 
etiology, medical/biologic plausibility, and patient condition (pre-existing condition). 

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 32 of 53 
7.1 
Adverse Event Definitions and Reporting 
 Adverse Event 
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other persons, whether or not 
related to the medical device under investigation.  This definition includes events related to the medical 
device under investigation and includes events related to the procedures involved. 
7.1.1.1 Adverse Event Reporting 
Safety surveillance and reporting starts as soon as the patient is enrolled in the clinical investigation 
(after consent is obtained and all eligibility criteria are met). Safety surveillance and reporting will 
continue until the last follow-up visit has been performed, the subject is deceased, the subject concludes 
participation in the clinical investigation or the subject withdraws from the clinical investigation. All 
adverse event data, including deaths, will be collected throughout the time period defined above and will 
be reported to the Sponsor on a CRF. Additional information with regard to an adverse event should be 
updated within the appropriate CRF.  
 
For the purposes of this study, the following adverse events will be reported: 
• 
Adverse events that are assessed by the investigator as being related to either the ablation 
catheter or the ablation procedure will be reported in the database, preferably within 7-days of the 
site learning of the event 
• 
Serious adverse events, regardless of relatedness to the procedure and/or the ablation catheter 
will be reported as described in Section 7.1.2.1. 
 
Recurrence of AF, AFL, or AT are not considered reportable adverse events unless they occur in 
severity, frequency, or other manner that is significantly worse than the subject’s baseline condition.  
Recurrence of AF, AFL, or AT will affect the primary effectiveness endpoint and should be reported on 
the Follow-Up Visit CRF.    
 
Additionally, urinary tract infections (UTIs) that occur after a procedure and do not require a Foley 
catheter will not be considered adverse events.  UTIs that require a Foley catheter will be reported as 
AEs if related to the procedure or meet serious criteria. 
 
Unchanged, chronic, non-worsening or pre-existing conditions are not AEs and should not be reported. 
 
All adverse events will be collected on each subject through the 15-month follow-up visit.  
 Serious Adverse Event (SAE) Reporting to Sponsor and IRB/EC 
If the AE meets any of the criteria below, it is regarded as a serious adverse event (SAE).  
a) Led to a death, 
b) Led to a serious deterioration in health of the subject, that either resulted in  
1. a life-threatening illness or injury, or 
2. a permanent impairment of a body structure or a body function, or 
3. in-patient hospitalization or prolongation of existing hospitalization, or 

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
Page 34 of 53 
8.2 
Statistical Analyses  
The primary endpoints and additional evaluation analyses will be summarized descriptively based on 
available data or measurements in the analysis population. No formal hypothesis testing will be 
performed. 
 Primary Safety Endpoint Analysis 
The primary safety endpoint will be summarized as the percentage of subjects who experienced one or 
more primary safety endpoints. The primary safety analysis population for the primary safety endpoint 
will be subjects in the primary analysis population who have completed their 7-day follow-up visit; or 
crossed the end of the 7-day visit window without the visit but with a primary safety endpoint event.  
Subjects without an event that are lost to follow up without a visit at or beyond their 7-day follow up visit 
window will be excluded from this analysis. 
 
The primary safety endpoint event rate will be calculated based on the number of subjects experiencing 
a primary safety endpoint event divided by the total number of subjects in the analysis population. 
Relatedness of the event to the catheter and to the procedure will be determined by the independent 
physician reviewer. 
 Additional Data Analyses 
Additional data to be collected in this clinical investigation are described and will be reported using 
summary statistics.  No hypothesis tests will be performed. 
 
In general, continuous (CONT) variables will be summarized with the numbers of observations, means 
with standard deviations, quartiles, minimums, maximums as per the table mockups.   
  
Categorical (CAT) variables will be summarized with subject counts and percentages/rates, and where 
specified in the table mockups. 
 
Survival (SURV) analysis will be conducted to analyze time-to-event variables.  Subjects without events 
will be censored at their last known event-free time point. Subjects withdrawn or otherwise lost to follow-
up during the follow-up period will be censored at their last known visit. Survival data will be presented 
using the Kaplan-Meier product limit method. 
 
The following list of analyses describes how the additional evaluations will be analyzed:  
 
• 
Acute procedural success, defined as confirmation of entrance block in all pulmonary veins (CAT) 
• 
Proportion of subjects off all Class I or III AADs taken to treat AF/AFL/AT at 15-months (SURV) 
• 
Proportion of subjects who achieve 15-month single procedure success, defined as freedom from 
documented AF/AFL/AT recurrence (episodes >30 seconds) during the 9-month period following 
the blanking and therapy consolidation periods after a single ablation procedure (SURV) 
• 
 
• 
Changes in EQ-5D-5L scores from baseline to follow-up at 3, 6, 12, and 15-months after the initial 
procedure (CONT) 

 
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Subjects providing informed consent are agreeing to allow clinical investigation monitors or regulatory 
authorities including foreign countries to review, in confidence, any records identifying the subjects in this 
clinical investigation. This information may be shared with regulatory agencies; however, Sponsor 
undertakes not to otherwise release the subject's personal and private information. 
10.0 QUALITY CONTROL AND QUALITY ASSURANCE 
10.1 Selection of Clinical Sites and Investigators 
The Sponsor will select investigators qualified by training and experience to participate in the clinical 
investigation. Sites will be selected based upon review of a recent site assessment, if applicable, and the 
qualifications of the investigators who will participate in the clinical investigation. 
10.2 CIP Amendments  
Approved CIP amendments will be provided to the Investigators by the Sponsor prior to implementing the 
amendment. The Principal Investigator is responsible for notifying the IRB/EC or equivalent committee of 
the CIP amendment (administrative changes) or obtaining IRB’s/EC’s approval of the CIP amendment 
(changes in subject care or safety), according to the instructions provided by the Sponsor with the CIP 
amendment.   
 
Acknowledgement/approval by the IRB/EC of the CIP amendment must be documented in writing prior to 
implementation of the CIP amendment. Copies of this documentation must also be provided to the 
Sponsor. 
10.3 Training 
 Site Training 
All Investigators and clinical investigation personnel are required to attend Sponsor training sessions, 
which may be conducted at an Investigator's meeting, a site initiation visit, or other appropriate training 
sessions. Over-the-phone or self-training may take place as required. Training of Investigators and 
clinical investigation personnel will include, but is not limited to, the CIP requirements, investigational 
device usage, electronic case report form completion and clinical investigation personnel responsibilities. 
All Investigators and clinical investigation personnel that are trained must sign a training log (or an 
equivalent) upon completion of the training. Prior to signing the training log, Investigators and clinical 
investigation personnel must not perform any CIP-related activities that are not considered standard of 
care at the site.  
 Training Required for the Use of the Device 
 
All investigators involved in the conduct of this clinical investigation will be qualified by education, 
training, or experience to perform their tasks and this training will be documented appropriately.  Each 
ablating physician must have contact force sensing experience and must have experience using EnSite 
Precision for AF treatment prior to site activation. 

 
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10.4 Monitoring  
Sponsor and/or designee will monitor the clinical investigation over its duration according to the CIP-
specific monitoring plan which will include the planned extent of source data verification.  
 
Prior to initiating any procedure, the Sponsor monitor (or delegate) will ensure that the following criteria 
are met:  
 
• 
The investigator understands and accepts the obligation to conduct the clinical investigation 
according to the CIP and applicable regulations and has signed the Clinical Trial Agreement.  
• 
The Investigator and his/her staff should have sufficient time and facilities to conduct the clinical 
investigation and should have access to an adequate number of appropriate subjects to conduct 
the clinical investigation.  
• 
Source documentation (including original medical records) must be available to substantiate 
proper informed consent procedures, adherence to CIP procedures, adequate reporting and 
follow-up of adverse events, accuracy of data collected on case report forms, and device 
information.  
• 
The Investigator/site will permit access to such records. A monitoring visit sign-in log will be 
maintained at the site. The Investigator will agree to dedicate an adequate amount of time to the 
monitoring process. The Investigator and/or research coordinator will be available for monitoring 
visits. It is expected that the Investigator will provide the monitor with a suitable working 
environment for review of clinical investigation-related documents. 
10.5 Deviations from CIP 
The Investigator should not deviate from the CIP for any reason except in cases of medical emergencies 
when the deviation is necessary to protect the rights, safety and well-being of the subject or eliminate an 
apparent immediate hazard to the subject. In that event, the Investigator will notify Sponsor immediately 
by phone or in writing.  
 
No waivers for CIP deviations will be granted by the Sponsor.  All deviations must be reported to the 
Sponsor using the Deviation CRF. The occurrence of CIP deviations will be monitored by the Sponsor for 
evaluation of investigator compliance to the CIP and regulatory requirements and dealt with according to 
written procedures. Investigators will inform their IRB/EC or equivalent committee of all CIP deviations in 
accordance with their specific IRB/EC or equivalent committee reporting policies and procedures.  
 
In the event of repeated non-compliance, as determined by the Sponsor, a Sponsor’s monitor or 
company representative will attempt to secure compliance by one or more of the following (and not 
limited to):  
• Visiting the investigator and/or delegate 
• Telephoning the investigator and/or delegate 
• Corresponding with the investigator and/or delegate 
 
Repeated non-compliance with the signed agreement, the CIP or any other conditions of the clinical 
investigation may result in further escalation in accordance with the Sponsor’s written procedures, 

 
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including securing compliance or, at its sole discretion, Sponsor may terminate the investigator's 
participation in the clinical investigation.  
10.6 Quality Assurance Audit 
A Sponsor representative or designee may request access to all clinical investigation records, including 
source documentation, for inspection during a Quality Assurance audit.  
 
In the event that an investigator is contacted by a Regulatory Agency in relation to this clinical 
investigation, the Investigator will notify Sponsor immediately. The Investigator and Research 
Coordinator must be available to respond to reasonable requests and audit queries made during the 
audit process. The Investigator must provide Sponsor with copies of all correspondence that may affect 
the review of the current clinical investigation (e.g., Form FDA 483, Inspectional Observations, Warning 
Letters, Inspection Reports, etc.). Sponsor may provide any needed assistance in responding to 
regulatory audits. 
10.7 Committees  
 Steering Committee  
The Steering Committee is responsible for overseeing the scientific and operational aspects of the 
clinical investigation. This committee will meet regularly to monitor subject enrollment, general data 
collection and non-compliance with the CIP at individual centers, to review operational issues that may 
arise and warrant a CIP amendment or other corrective action and to determine policy regarding any 
publications arising from data generated from the performance of the clinical investigation. 
11.0 DATA HANDLING AND RECORD KEEPING  
Sponsor and/or its affiliates will maintain documentation of the systems and procedures used in data 
collection for the duration of the clinical investigation.  
 
CRF data collection will be performed through a secure web portal and only authorized personnel will 
access the Electronic Data Capture (EDC) system using a unique username and password to enter, 
review or correct data. Passwords and electronic signatures will be strictly confidential.   
 
The data will be subjected to consistency and validation checks within the EDC system and 
supplemental review by the Sponsor.    
 
At the conclusion of the clinical investigation, completed CRF images with the date-and-time stamped 
electronic audit trail indicating the user, the data entered, and any reason for change (if applicable) will 
be provided to the investigational sites.  
 
For the duration of the clinical investigation, the Investigator will maintain complete and accurate 
documentation including, but not limited to, medical records, clinical investigation progress records, 
laboratory reports, CRFs, signed ICFs, device accountability records (if applicable), correspondence with 
the IRB/EC and clinical investigation monitor/Sponsor, adverse event reports, and information regarding 
subject discontinuation or completion of the clinical investigation. 

 
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11.1 Protection of Personally Identifiable Information 
The Sponsor respects and protects personally identifiable information collected or maintained for this 
clinical investigation.  
 
The Sponsor implements technical and physical access controls to ensure that Personal Information is 
accessible only to and processed only on a ‘need to know’ basis, including periodic review of access 
rights, and revocation of access when an individual’s employment is terminated or the individual 
transitions to a role that does not require access to Personal Information, and appropriate restrictions on 
physical access to premises, facilities, equipment, and records containing Personal Information. 
 
The Sponsor requires the investigational sites to transfer into Sponsor’s data management systems only 
pseudonymous Personal Information (key-coded) necessary to conduct the Clinical Investigation, such 
as the patient’s medical condition, treatment, dates of treatment, etc. The Sponsor discloses as part of 
the clinical investigation informed consent process that some Sponsor representatives still may see 
Personal Information at the participating sites for technical support of the participating physicians on the 
device implant or procedures, monitoring and quality control purposes. Confidentiality of Personal 
Information will be observed by all parties involved at all times throughout the clinical investigation. The 
privacy of each subject and confidentiality of his/her information will be preserved in reports and when 
publishing any data. 
 
The Sponsor data management systems and processes were designed, developed, and tested 
according to industry standards to appropriately safeguard Confidential Information (including any 
Personal Information) against unauthorized access and/or interference by third parties, intrusion, theft, 
destruction, loss or alteration. Clinical Investigation data are encrypted in transit and at rest.  
 
The Sponsor maintains a Privacy Incident procedure that complies in all respects with Applicable Law 
and industry best practices. 
11.2 Data Management Plan 
A Data Management Plan (DMP) will describe procedures used for data review, data cleaning, and 
issuing and resolving data discrepancies. If appropriate, the DMP may be updated throughout the 
duration of the clinical investigation. All revisions will be tracked and document controlled. 
11.3 Source Documentation  
Regulations and GCP require the Investigator to maintain information in the subject’s original medical 
records that corroborates data collected on the CRFs. In order to comply with these regulatory 
requirements/GCP, the following information should be included in the subject record at a minimum and 
if applicable to the clinical investigation: 
• 
Medical history/physical condition of the subject before involvement in the clinical investigation 
sufficient to verify CIP entry criteria 
• 
Dated and signed notes on the day of entry into the clinical investigation referencing the Sponsor, 
CIP number, subject ID number and a statement that informed consent was obtained 
• 
Dated and signed notes from each subject visit (for specific results of procedures and exams) 

 
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• 
Adverse events reported and their resolution, including supporting documents, such as discharge 
summaries, catheterization laboratory reports, ECGs, and lab results including documentation of 
site awareness of SAEs and of investigator assessment of device relationship for SAEs. 
• 
CIP-required laboratory reports and 12-lead ECGs, reviewed and annotated for clinical 
significance of out of range results. It is acceptable to have labs and/or ECGs reviewed and 
annotated in the electronic medical record system for site’s that have these capabilities.  For 
those sites that do not have such capability, the labs and ECGs should be printed and signed by 
the investigator.  
• 
Notes regarding CIP-required and prescription medications taken during the clinical investigation 
(including start and stop dates) 
• 
Subject’s condition upon completion of or withdrawal from the clinical investigation 
• 
Any other data required to substantiate data entered into the CRF 
• 
Patient reported outcome measures may be completed using CRF worksheets. These serve as 
the source documentation. 
11.4 Case Report Form Completion  
Worksheets will be provided to sites under separate cover for review of the required data collection for 
the trial.  Sites may also create their own worksheets for data collection. 
 
Primary data collection based on source-documented hospital and/or clinic chart reviews will be 
performed clearly and accurately by site personnel trained on the CIP and CRF completion. The 
investigator will ensure accuracy, completeness, legibility and timeliness of the data reported to the 
Sponsor on the CRFs and in all required reports.  Data will be collected on CRFs for all subjects that are 
enrolled in the clinical investigation.   
 
Only authorized site personnel will be permitted to enter the CRF data through the EDC system deployed 
by the Sponsor. An electronic audit trail will be used to track any subsequent changes of the entered 
data. 
11.5 Record Retention 
The Sponsor and Investigator/Site will archive and retain all documents pertaining to the clinical 
investigation as per the applicable regulatory record retention requirements. The Investigator must obtain 
permission from Sponsor in writing before destroying or transferring control of any clinical investigation 
records. 
12.0 ETHICAL CONSIDERATION 
 
12.1 Institutional Review Board/Medical Ethics Committee Review and Approval 
Institutional Review Board (IRB)/ Ethics Committee (EC) approval for the CIP and ICF/other written 
information provided to the patient will be obtained by the Principal Investigator at each investigational 
site prior to consenting and enrolling patients in this clinical investigation. The approval letter must be 
received prior to the start of this clinical investigation and a copy must be provided to the Sponsor.  
 

 
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Any amendments to the CIP as well as associated ICF changes will be submitted to the IRB/EC and 
written approval obtained prior to implementation, according to each institution’s IRB/EC requirements.  
 
No changes will be made to the CIP or ICF or other written information provided to the patient without 
appropriate approvals, including IRB/EC, the Sponsor, and the regulatory agencies (if applicable).  
 
Until the clinical investigation is completed, the Investigator will advise his/her IRB/EC of the progress of 
this clinical investigation, per IRB/EC requirements. Written approval must be obtained from the IRB/EC 
yearly to continue the clinical investigation, or according to each institution’s IRB/EC requirements.  
 
No investigative procedures other than those defined in this CIP will be undertaken on the enrolled 
subjects without the written agreement of the IRB/EC and the Sponsor. 
13.0 CLINICAL INVESTIGATION CONCLUSION 
The clinical investigation will be concluded when: 
• 
All sites are closed AND 
• 
The clinical investigation report will be provided to investigators within one year of the end of the 
investigation and the Sponsor has provided formal documentation of clinical investigation closure.  
14.0 PUBLICATION POLICY 
The data and results from the clinical investigation are the sole property of the Sponsor. The Sponsor 
shall have the right to access and use all data and results generated during the clinical investigation. The 
Investigators will not use this clinical investigation-related data without the written consent of the Sponsor 
for any purpose other than for clinical investigation completion or for generation of publication materials, 
as referenced in the Clinical Trial Agreement. Single-center results are not allowed to be published or 
presented before the multi-center results. Any proposals for publications or presentations by the 
investigators must be reviewed and approved by the Sponsor in a timely manner to enable Sponsor 
review in compliance with the Sponsor’s publication policy set forth in the Clinical Trial Agreement. 
 
The Sponsor will be responsible for determining whether to register the clinical investigation on 
www.clinicaltrials.gov or any other clinical trials, in accordance with the International Committee of 
Medical Journal Editors guidelines, or any other applicable guidelines. In the event Sponsor determines 
that the clinical investigation should be registered, Sponsor shall be responsible for any such registration 
and results posting as required by the ClinicalTrials.gov website. Institution and/or Principal 
Investigator(s) shall not take any action to register the clinical investigation. 
15.0 RISK ANALYSIS 
 
Risks associated with the device are managed in accordance with ISO 14971. The risk analysis included 
an objective review of published and available unpublished medical and scientific data. The sections 
below provide an overview of residual risks identified in the risk management report and anticipated 
benefits of the medical device. The additional tests and assessments required by the clinical 
investigation were analyzed for additional risks and are incorporated in the sections below. 

 
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15.1 Anticipated Clinical Benefits 
While there is no guaranteed clinical benefit associated with participation in this study, it is expected that 
TactiCath SE will have similar benefits as other commercially available ablation catheters in maintaining 
sinus rhythm. The clinical benefits of sinus rhythm are well established and include relief of symptoms 
and improvements in exercise tolerance, hemodynamics, LV function, and quality of life. Restoration of 
sinus rhythm may confer a mortality benefit. 
 
The information gathered from this study will also add to the understanding of the treatment options for 
subjects with persistent AF. This knowledge may advance medical science and have a benefit on other 
subjects with a similar arrhythmia. 
15.2 Foreseeable Adverse Events and Anticipated Adverse Device Effects 
Risks associated with the specified device and procedure are listed below.  There may be risks related to 
the device under investigation that are unknown at present.  Likewise, the exact frequency of the risk 
may be unknown. 
 
The following is a list of anticipated adverse device effects:   
 
• 
Air embolism 
• 
Anesthesia reaction 
• 
Aorto-right atrial fistula 
• 
Arrhythmias, bradycardia, and tachycardia 
• 
Arteriovenous fistula 
• 
Cardiac perforation/tamponade 
• 
Cardiac thromboembolism 
• 
Cerebrovascular incident or Attack / Stroke 
• 
Chest pain/discomfort 
• 
Coronary artery dissection 
• 
Coronary artery spasm 
• 
Coronary artery thrombosis / occlusion 
• 
Death 
• 
Diaphragmatic paralysis 
• 
Dislodgement of implantable cardioverter defibrillator or permanent pacing leads 
• 
Endocarditis 
• 
Gastroparesis 
• 
Heart failure / pump failure 
• 
Hemothorax 
• 
Hospitalization (initial and prolonged) 
• 
Increased creatinine phosphokinase (CPK) level 
• 
Infections 
• 
Laceration 
• 
Leakage of air or blood into the lungs or other organs due to perforation 
• 
Left atrial-esophageal fistula 
• 
Major bleeding, requiring surgery or transfusion 
• 
Myocardial infarction 
• 
Obstruction or perforation or damage to the vascular system 

 
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• 
Pericarditis 
• 
Pericardial effusion 
• 
Phrenic nerve damage including diaphragmatic paralysis 
• 
Pleural effusion 
• 
Pneumonia 
• 
Pneumothorax 
• 
Pseudoaneurysm 
• 
Pulmonary edema 
• 
Pulmonary embolism 
• 
Pulmonary vein dissection 
• 
Pulmonary vein thrombus 
• 
Pulmonary hypertension 
• 
Respiratory depression 
• 
Skin burns 
• 
Severe PV stenosis (>70%), or complete occlusion of a PV, even in the absence of symptoms 
• 
Tamponade, potentially requiring surgery 
• 
Temperature elevation or fever 
• 
Transient ischemic attack (TIA) 
• 
Thromboembolism 
• 
Thrombosis 
• 
Unintended complete or incomplete AV, sinus node, or other heart block or damage 
• 
Valvular damage 
• 
Vascular bleeding/local hematomas/ecchymosis 
• 
Vasovagal reactions 
• 
Ventricular tachyarrhythmia 
• 
Volume overload 
15.3 Residual Risks Associated with the Device Under Investigation, as Identified in the 
Risk Analysis Report 
The risk analysis for TactiCath SE was performed based on in-house tools to systematically identify 
potential hazards associated with the design and use of the device.   Based upon the preclinical, clinical 
(Earliest generation of catheter – TOCCATA trial (NCT01223469), EFFICAS I and II trials 
(NCT02131337), TOCCASTAR trial (NCT01278953), Next generation of catheter - TOCCASTAR 
Supplemental Clinical Study (NCT01278953), and TactiCath Quartz Post Approval Study 
(NCT02310100)) and bench-testing data, all risks have been identified and determined to be within 
acceptable levels.  
No additional residual risk has been identified with the use of the TactiCath SE catheter. 
15.4 Risks Associated with Participation in this Clinical Investigation 
Possible risks associated with participating in this clinical study are not anticipated to be any different 
from risks associated with undergoing procedures with commercially available TactiCath SE. Protocol 
required assessments are summarized in Section 6.7.3. These assessments are standard of care for 
TactiCath SE and as such do not pose any additional risks.  

 
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15.5 Possible Interactions with Protocol-Required Concomitant Medications  
There are no known interactions with protocol-required concomitant medications. 
15.6 Steps Taken to Control or Mitigate Risks 
In-depth recommendations, special precautions and instructions regarding patient selection, device 
handling, and device placement are included in the IFU.  It is also stated in the IFU that the devices can 
only be used by physicians who have received appropriate training on how to use the device. This 
statement is interpreted to mean that the physician users are expected to be aware of the known and 
foreseeable safety risks associated with the use of the device including the surgical and/or non-surgical 
treatment of these conditions. 
 
Risks associated with the use of the device under investigation are minimized through device design, 
investigator selection and training, pre-specified patient eligibility requirements, and study monitoring to 
ensure adherence to the protocol. All adverse events will be reported to the Sponsor as summarized in 
Sections 7.1.1.1 - 7.1.1.4 and will be monitored internally for safety surveillance purposes. 
 
Device Design: The catheter has a contact force magnetic sensor which plays an important factor in 
achieving transmural lesions that is critical in abolishing the substrate necessary for an arrhythmia and 
AF in particular. With increasing force, a greater proportion of the electrode surface area is in 
contact with the tissue, and there is more efficient energy coupling. Gaps in ablation lines are commonly 
seen when the amount of contact force over the RF delivery time is low and this is associated with higher 
recurrence rates after ablation for AF. Contact force-sensing ablation catheters such as TactiCath SE 
provide a valuable feedback mechanism to help ensure the efficacy of ablation. 
 
Investigator Selection and Training: Investigators will be selected as outlined in Section 10.1.  Sites will 
receive training as stated in Section 10.3.1. Additionally, ablating physicians will be qualified and have 
experience using a contact force sensor as stated in Section 10.3.2. 
 
Adherence to the Clinical Investigational Protocol:  The clinical study will be monitored by the 
Sponsor to ensure adherence to the CIP.  Subjects will be carefully selected through rigorous screening 
using pre-specified inclusion and exclusion criteria as stated in Section 5.3. Adverse events will be 
reported to the Sponsor and will be monitored internally for safety surveillance purposes and reported to 
regulatory authorities as applicable. Adverse events will be adjudicated by qualified physicians who are 
not participating in the study.   
15.7 Risk to Benefit Rationale 
An extensive risk analysis and risk mitigation plan (as summarized in Section 15.3) has been 
implemented to minimize any residual risk of the TactiCath SE to the subject. Treatment with TaciCath 
SE has all the benefits of a state-of-the-art cardiac ablation therapy with the added benefit being able to 
monitor contact force at the catheter tip. The residual risks are outweighed by the benefits, as described 
in the previous sections, and the overall risk has been determined to be acceptable.  
16.0 REFERENCES 
1. 
Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a Global 
Burden of Disease 2010 Study. Circulation 2014;129:837-47. 

 
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2. 
Murakoshi N, Aonuma K. Epidemiology of Arrhythmias and Sudden Cardiac Death in Asia. 
Circulation Journal 2013;77:2419-31. 
3. 
Wong CX, Brown A, Tse H-F, et al. Epidemiology of Atrial Fibrillation: The Australian and Asia-
Pacific Perspective. Heart Lung and Circulation 2017;26:870-9. 
4. 
January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of 
patients with atrial fibrillation: executive summary: a report of the American College of 
Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm 
Society. Circulation 2014;130:2071-104. 
5. 
Parkash R, Verma A, Tang AS. Persistent atrial fibrillation: current approach and controversies. 
Current opinion in cardiology 2010;25:1-7. 
6. 
Calkins H, Kuck KH, Cappato R, et al. 2012 HRS/EHRA/ECAS expert consensus statement on 
catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural 
techniques, patient management and follow-up, definitions, endpoints, and research trial design: a 
report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial 
Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a 
registered branch of the European Society of Cardiology (ESC) and the European Cardiac 
Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), 
American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the 
Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of 
Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, 
the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart 
Rhythm Society, and the Heart Rhythm Society. Heart rhythm 2012;9:632-96 e21. 
7. 
Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert 
consensus statement on catheter and surgical ablation of atrial fibrillation. Heart rhythm 
2017;14:e275-e444. 
8. 
Reddy VY, Shah D, Kautzner J, et al. The relationship between contact force and clinical outcome 
during radiofrequency catheter ablation of atrial fibrillation in the TOCCATA study. Heart rhythm 
2012;9:1789-95. 
9. 
Neuzil P, Reddy VY, Kautzner J, et al. Electrical reconnection after pulmonary vein isolation is 
contingent on contact force during initial treatment: results from the EFFICAS I study. Circulation 
Arrhythmia and electrophysiology 2013;6:327-33. 
10. Kautzner J, Neuzil P, Lambert H, et al. EFFICAS II: optimization of catheter contact force improves 
outcome of pulmonary vein isolation for paroxysmal atrial fibrillation. Europace : European pacing, 
arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, 
arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 
2015;17:1229-35. 
11. Reddy VY, Dukkipati SR, Neuzil P, et al. Randomized, Controlled Trial of the Safety and 
Effectiveness of a Contact Force-Sensing Irrigated Catheter for Ablation of Paroxysmal Atrial 
Fibrillation: Results of the TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation 
(TOCCASTAR) Study. Circulation 2015;132:907-15. 

 
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APPENDIX II. ABBREVIATIONS AND ACRONYMS 
All relevant abbreviations and acronyms specific to this clinical investigation are outlined in the table 
below. 
 
Acronym/Abbreviation 
Description 
AAD 
Antiarrhythmic drug 
AE 
Adverse event 
AF 
Atrial fibrillation 
AFL 
Atrial flutter 
APHRS 
Asia Pacific Heart Rhythm Society 
AT 
Atrial tachycardia 
CFAE 
Complex fractionated atrial electrograms 
CIP 
Clinical investigation plan 
CRF 
Case report form 
CRT-D 
Cardiac resynchronization therapy defibrillator 
CTI 
Cavotricuspid isthmus 
CVA 
Cerebrovascular accident 
DMP 
Data Management Plan 
EC 
Ethics Committee 
ECAS 
European Cardiac Arrhythmia Society 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
EHRA 
European Heart Rhythm Association 
EQ 
EuroQol Group 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HRS 
Heart Rhythm Society 
ICE 
Intracardiac echocardiography 
ICD 
Implantable cardioverter defibrillator  
ICF 
Informed Consent form 
IDE 
Investigational device exemption 
IFU 
Instructions for Use 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
LAD 
Left atrial diameter 
LCD 
Liquid crystal display 
LVEF 
Left ventricular ejection fraction 
MI 
Myocardial infarction 
NIHSS 
National Institutes of Health Stroke Scale 
NOAC 
Novel oral anticoagulant 
NYHA 
New York Heart Association 
OPC 
Objective performance criterion 
PCI 
Percutaneous coronary intervention 
PMA 
Pre-market approval 
PTE 
Per treatment evaluable 

 
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Acronym/Abbreviation 
Description 
PV 
Pulmonary vein 
RF 
Radiofrequency 
SAE 
Serious adverse event 
SE 
Sensor enabled 
SOLAECE 
Latin America Society of Electrophysiology and 
Cardiac Stimulation 
SVT 
Supraventricular tachycardia 
TEE 
Transesophageal echocardiogram 
TIA 
Transient ischemic attack 
TTE 
Transthoracic echocardiogram 
TTM 
Transtelephonic monitoring 
UADE 
Unanticipated adverse device effect 
UTI 
Urinary tract infection 
 
 
 

 
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APPENDIX III.  DEFINITIONS 
The following definitions will be used by the independent, qualified physicians that will determine whether 
the events listed below constitute a device or procedure related serious adverse event included in the 
primary endpoint.  Most of the definitions have been adapted from the 2017 
HRS/EHRA/ECAS/APHRS/SOLAECE Expert Consensus on AF Ablation.7 
 
Primary Safety Event 
Description 
Atrioesophageal fistula 
A connection between the atrium and the lumen of the esophagus.  Evidence supporting 
this diagnosis includes documentation of esophageal erosion combined with evidence of a 
fistulous connection to the atrium, such as air emboli, an embolic event, or direct 
observation at the time of surgical repair.  A CT scan or MRI scan is the most common 
method of documentation of an atrioesophageal fistula. 
Bleeding 
Bleeding is a major complication of AF ablation if it requires and/or is treated with 
transfusion or results in a 20% or greater fall in hematocrit.  
Cardiac tamponade/perforation 
The development of a significant pericardial effusion during or within 30 days of 
undergoing an AF ablation procedure.  A significant pericardial effusion is one that results 
in hemodynamic compromise, requires elective or urgent pericardiocentesis, or results in a 
1-cm or more pericardial effusion as documented by echocardiography.  Cardiac 
tamponade/perforation should also be classified as “early” or “late” depending on whether 
it is diagnosed during or following initial discharge from the hospital. 
Death 
Adverse event resulting in the patient’s death. 
Heart block (AV block) 
New, persistent 2nd or 3rd degree AV block not attributable to a vasovagal reaction or 
medication effect and requiring permanent pacing. 
Myocardial infarction  
Irreversible necrosis of heart muscle secondary to prolonged ischemia with at least one of 
the following three criteria: 
(2) Detection of ECG changes indicative of new ischemia (new ST-T wave changes or 
new LBBB) that persist for more than 1 hour; 
(3) Development of new pathological Q waves on an ECG; 
(4) Imaging evidence of new loss of viable myocardium or new regional wall motion 
abnormality. 
Pericarditis 
Pericarditis should be considered a major complication following ablation if it results in an 
effusion that leads to hemodynamic compromise or requires pericardiocentesis, prolongs 
hospitalization by more than 48 hours, requires hospitalization, or persists for more than 
30 days following the ablation procedure. 
Phrenic nerve injury resulting in 
diaphragmatic paralysis 
Phrenic nerve paralysis is defined as absent phrenic nerve function as assessed by a sniff 
test.  A phrenic nerve paralysis is considered to be permanent when it is documented to 
be present 12 months or longer following ablation. 
Pneumothorax 
Abnormal collection of air in the pleural space between the lung and the chest wall that 
prolongs the hospital stay (for observation) or requires surgical intervention or chest tube 
placement. 
Pulmonary edema 
Excess fluid in the lungs that includes all of the following: 
• 
Symptoms (e.g. dyspnea) 
• 
Physical findings (e.g. rales, hypoxemia) 
• 
Radiologic findings 
• 
Response to diuretic therapy  
• 
Requires hospitalization 
Pulmonary vein stenosis 
Reduction of the diameter of a pulmonary vein or a pulmonary vein branch of ≥70% 
confirmed via imaging (CT or MRI). 
Stroke / cerebrovascular accident 
Stroke diagnostic criteria: 

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
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Primary Safety Event 
Description 
• 
Rapid onset of a focal or global neurological deficit with at least one of the 
following: change in level of consciousness, hemiplegia, numbness or sensory 
loss affecting one side of the body, dysphasia or aphasia, hemianopia, 
amaurosis fugax, or other neurological signs or symptoms consistent with stroke 
• 
Duration of a focal or global neurological deficit ≥24 hours; OR <24 hours if 
therapeutic intervention(s) were performed (e.g. thrombolytic therapy or 
intracranial angioplasty); OR available neuroimaging documents a new 
hemorrhage or infarct; OR the neurological deficit results in death. 
• 
No other readily identifiable nonstroke cause for the clinical presentation (e.g. 
brain tumor, trauma, infection, hypoglycemia, peripheral lesion, pharmacological 
influences). 
• 
Confirmation of the diagnosis by at least one of the following:  neurology or 
neurosurgical specialist; neuroimaging procedure (MRI or CT scan or cerebral 
angiography); lumbar puncture (i.e. spinal fluid analysis diagnostic of intracranial 
hemorrhage) 
Thromboembolism 
An arterial or venous thrombus that results in deep vein thrombosis, pulmonary embolism, 
or peripheral arterial embolism. 
Transient ischemic attack 
New focal neurological deficit of vascular (occlusive) origin with rapid symptom resolution 
(usually 1 to 2 hours), always within 24 hours determined by the consulting neurologist; 
neuroimaging without tissue injury. 
Vascular access complication 
Vascular access complications include development of a hematoma, an AV fistula, or a 
pseudoaneurysm.  A major vascular complication is defined as one that requires 
intervention, such as surgical repair or transition, prolongs the hospital stay, or requires 
hospital admission. 
 
 

 
Study Name: PerAF APAC 
Clinical Investigation Plan 
 
 
 
 
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