TactiCath® Contact Force Ablation Catheter Study for Atrial Fibrillation Post Approval Study
Phase: NA
Conditions: Paroxysmal Atrial Fibrillation
Sponsor: Abbott Medical Devices

 
Clinical Investigation Plan Cover Page 
 
 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott. 
87173 CIP Posting Cover Page Ver B 
Template 
Page 1 of 1 
 
NCT Number: 02310100 
TOCCASTAR CAP (Appendix K in Protocol) 
TactiCathTM 
Contact Force Ablation Catheter Study for Atrial Fibrillation 
Continued Access Study 
Study Document No: SJM-CIP-10031 
Version H 
Date: 21-JAN-2014 
 
 
Sponsor  
 
 
St. Jude Medical, Inc. 
        
 
 
 
One St. Jude Medical Drive 
      
  
 
 
St. Paul, MN 55117 
        
 
 
 
United States 
 
 
 

 
 
TactiCath® Contact Force Ablation 
Catheter Study for Atrial Fibrillation 
 
 
A prospective, randomized, multicenter, interventional study to evaluate the safety and 
effectiveness of the TactiCath® percutaneous ablation catheter for the treatment of symptomatic 
paroxysmal atrial fibrillation using contact force assisted irrigated radiofrequency ablation 
 
CLINICAL 
INVESTIGATIONAL 
PLAN: 
VP-002 527 
INVESTIGATIONAL 
DEVICE: 
TactiCath® Set and the TactiCath Quartz Set  - a 
percutaneous catheter and system components for irrigated 
radiofrequency ablation, incorporating contact force 
sensing  
CIP DATE: 
Version H 
 January 21, 2014 
SPONSORED BY: 
Endosense 
42 Chemin du Grand-Puits 
1217 Meyrin Geneva 
Switzerland 
41-22-306-1960 
MANUFACTURER: 
Endosense 
CONTRACT 
RESEARCH 
ORGANIZATION: 
Premier Research Group Limited 
1500 Market Street, Suite 3500W 
Philadelphia, PA 19102 
United States 
1-215-282-5500 
Information contained in this clinical investigational plan is confidential in nature, and may not be 
used, divulged, published or otherwise disclosed to others except to the extent necessary to obtain 
approval of the Institutional Review Board or Independent Ethics Committee, or as required by law. 
Persons to whom this information is disclosed should be informed that this information is confidential 
and may not be further disclosed without the express permission of Endosense. 

 
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SIGNATURES OF AGREEMENT 
 
 
Hendrik Lambert, PhD 
Vice President Clinical and Regulatory Affairs, 
Endosense 
 
 
Date 
 
David Harari 
Director, US Clinical Affairs, Endosense 
 
 
Date 
 
Valerie Dubois 
Quality Manager, Endosense 
 
 
Date 
 
Nabil Kanaan 
Director Clinical Affairs, St. Jude Medical 
 
 
 
Date 
 
Vini Doraiswamy 
Vice President Global Clinical Operations, St. Jude 
Medical 
 
 
 
Date 
 
Vivek Reddy, MD 
Principal Investigator; Professor of Medicine, Mount 
Sinai School of Medicine; Director, Cardiac Arrhythmia 
Service, Mount Sinai Hospital 
 
 
 
Date 

 
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Revision History 
VP-002 527 Clinical Investigational Plan 
 
Revision H – January 21, 2014 
Change 
Rationale 
Introduction  (Sect 3) 
Update description of Continued Access Study (Sect 3.9) 
Study Design (Sect 7) 
Amended description of study procedures related to the requirements 
for trans-esophageal echocardiography (TEE) and anticoagulation (Sect 
7.5)  
Study Procedures (Sect 10) 
Specified no requirement for CT/MR scans (Sect 10.2.1, 10.5.2) and no 
randomization (Sect 10.2.2) for Clinical Access Study subjects 
Continued Access Study 
(Appendix K) 
Amended description of study procedures related to the requirements 
for trans-esophageal echocardiography (TEE) and anticoagulation (K.7) 
 
Revision G – December 12, 2013 
Change 
Rationale 
Clinical Investigation Synopsis 
(Sect 2) 
Added reference to Continued Access Study 
Introduction (Sect 3) 
Added description of Continued Access Study (Sect 3.9) 
Study Design (Sect 7) 
Added description of Continued Access Study procedures (Sect 7.5)  
Schedule of Activities (Sect 9) 
Added reference to Continued Access Study procedures in Appendix K 
Study Procedures (Sect 10) 
Clarified allowable use of previously prescribed AADs in the Continued 
Access Study (Sect 10.9.2) 
References (Sect 20) 
Added reference for 2012 HRS/EHRA/ECAS Consensus Statement on 
AF (Ref. 30) 
Continued Access Study 
(Appendix K) 
Added complete description of Supplemental Clinical Study including 
Introduction (K.1), Device Description (K.2), Study Purpose and 
Objectives (K.3), Study Endpoints (K.4), Study Design (K.5), Criteria 
for Eligibility (K.6), Study Procedures (K.7), Patient Benefits and Risks 
(K.8), Adverse Events (K.9), Clinical Events Committee (K.10), 
Protocol Deviations (K.11), Ambulatory Monitoring (K.12), Oversight 
(K.13) and Omissions (K.14) 
 
Revision F – October 31, 2012 
Change 
Rationale 
Clinical Investigation Synopsis 
(Sect 2) 
Added reference to Supplemental Clinical Study 
Introduction (Sect 3) 
Added TOCCASTAR study update and description of Supplemental 
Clinical Study (Sect 3.8) 
Study Design (Sect 7) 
Added description of Supplemental Clinical Study procedures (Sect 7.4)  

 
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Schedule of Activities (Sect 9) 
Corrected mislabeled test for anti-coagulation, removed reference to 
hepatic function test, added reference to QoL at 12 months (Table 1) 
Study Procedures (Sect 10) 
Specified no requirement for CT/MR scans (Sect 10.2.1, 10.5.2) and no 
randomization (Sect 10.2.2) for Supplemental Clinical Study subjects 
Statistical Methodology 
(Appendix A) 
Clarified Interim Analysis plan for consistency with final analysis (Sect 
A.2) 
Supplemental Clinical Study 
(Appendix J) 
Added complete description of Supplemental Clinical Study including 
Introduction (J.1), Intended Use and Device Description (J.2), Study 
Purpose and Objectives (J.3), Study Endpoints (J.4), Study Design (J.5), 
Criteria for Eligibility (J.6), Study Procedures (J.7), Patient Benefits and 
Risks (J.8), Adverse Events (J.9) and Omissions (J.10) 
 
Revision E – April 18, 2011 
Change 
Rationale 
Study Endpoints (Sect 6) 
Included additional contact force parameters obtained from the TactiSys 
Procedure Summary Report in the analysis of descriptive endpoints 
(Sect 6.3.1) 
Study Design (Sect 7) 
Added extended follow-up every 6 months after effectiveness 
assessment period through device approval. Added reference to 
expected post-approval study requirement (Sect 7.4) 
Schedule of Activities (Sect 9) 
Added extended follow-up requirement, deleted NYHA assessment at 
pre-discharge and 7-day follow-ups (Table 1) 
Study Procedures (Sect 10) 
Specified window for baseline CT/MR scans as 60 days prior to 
procedure (Sect 10.2.1, #13) 
 
Clarified procedure for phrenic nerve integrity test (Sect 10.3, #13) 
 
Deleted NYHA assessment procedure at pre-discharge (Sect 10.4) 
 
Added reference to expected post-approval study requirement (Sect 
10.5) 
 
Deleted NYHA assessment procedure at 7-day follow-up (Sect 10.5.1) 
 
Added Extended Follow-up Procedure (Sect 10.5.5) 
 
Added Post-approval Study Procedure (Sect 10.5.6) 
Adverse Events (Sect 12) 
Amended SAE reporting requirement for investigators to 7 days (Sect 
12.4) 
 
Amended SAE reporting requirement to IRBs to 7 days (Sect 12.4.2) 
Ethics (Sect 15) 
Provided for access to ECRF by the independent clinical lab to enter 
TTM and Holter data (Sect 15.4) 
Statistical Methodology 
(Appendix A) 
Revised subgroup analysis description (Appendix A.6) 
Ambulatory Monitoring Services 
(Appendix F) 
Added description of ambulatory monitoring services vendor (Appendix 
F) 
 

 
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Revision D – December 21, 2010 
Change 
Rationale 
Study Endpoints (Sect 6) 
Rephrased primary safety endpoint definition to include all patients in 
whom a study device is introduced (Sect 6.1.2) 
Study Procedures (Sect 10) 
Deleted reference to endpoint exclusion if PVI not attempted (Sect 10.3, 
#8) 
 
Amended maximum power limit in TactiCath group to 40W and 
reiterated use of control device per labeling (Sect 10.3, #10) 
 
Amended recommendation for power settings using TactiCath (Sect 
10.3.1) 
Adverse Events (Sect 12) 
Deleted reference to endpoint exclusion if PVI not attempted (Sect 12.2) 
Statistical Methodology 
(Appendix A) 
Deleted reference to endpoint exclusion if PVI not attempted (Appendix 
A.5.1) 
 
Added additional sensitivity analyses for primary safety endpoint 
(Appendix A.5.3) 
 
Reworded subgroup analysis description (Appendix A.6) 
 
Added gender subgroup (Appendix A.6) 
 
Added sensitivity analyses (Appendix A.8) 
 
Revision C – November 5, 2010 
Change 
Rationale 
Study Endpoints (Sect 6) 
Amended primary effectiveness endpoint to include all 4 PVs. Clarified 
chronic success definition to include acute success (Sect 6.1.1) 
 
Clarified primary safety endpoint definition with respect to device 
relatedness (Sect 6.1.2) 
 
Amended secondary safety endpoint to include all SAEs (Sect 6.2.2) 
Study Design (Sect 7) 
Deleted reference to successor control device (Sect 7) 
 
Amended study population to include attrition in enrollment ceiling 
(Sect 7.2) 
 
Amended follow-up requirements for roll-in patients (Sect 7.3) 
 
Clarified the use of device for re-ablation during blanking (Sect 7.4) 
 
Specified documentation for patient withdrawal (Sect 7.5) 
Criteria for Eligibility (Sect 8) 
Added independent exclusion for prior cardioversions (Sect 8.2) 
Schedule of Activities (Sect 9) 
Amended expected start/completion dates (Sect 9) 
 
Added footnote regarding follow-up scans if evidence of stenosis at 3 
months (Table 1) 
Study Procedures (Sect 10) 
Deleted hepatic function test requirement (Sect 10.2.1) 
 
Amended requirement for TEE within 24 hours (Sect 10.2.1) 

 
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Clarified the use of device for LA ablations (Sect 10.3) 
 
Added intra-operative exclusion if AVRT/AVNRT and no PVI 
attempted (Sect 10.3) 
 
Added max power requirement (Sect 10.3) 
 
Added requirement to pace-test for phrenic nerve damage (Sect 10.3) 
 
Added requirement for minimum level of anticoagulation (Sect 10.3) 
 
Amended recommendation for power titration (Sect 10.3.1) 
 
Clarified the calculation of windows for follow-up procedures (Sect 
10.5) 
 
Added Re-ablation Procedure (Sect 10.6) 
 
Added Imaging for PV Stenosis (Sect 10.7) 
Patient Benefits and Risks (Sect 
11) 
Amended Clinical Risk Analysis (Sect 11.4) 
Adverse Events (Sect 12) 
Added definition for excluded AEs (Sect 12.1.1) 
 
Clarified primary SAE definition with respect to device relatedness 
(Sect 12.2) 
Statistical Methodology 
(Appendix A) 
Reorganized Section A.1, added Sample Size (Appendix A.1.3) 
 
Amended interim analyses rationale and sample size to include attrition 
(Appendix A.2) 
 
Deleted reference to successor control device (Appendix A.3) 
 
Amended primary effectiveness endpoint to include all 4 PVs. Clarified 
chronic success definition to include acute success (Appendix A.5.2.1) 
 
Clarified exploratory analyses for sub-optimal results (Appendix 
A.5.2.1) 
 
Clarified determination of confidence intervals and definition of 
primary analysis population for effectiveness (Appendix A.5.2.1) 
 
Clarified secondary endpoint analysis methodology and analysis 
population (Appendix A.5.2.2) 
 
Amended descriptive analysis population (Appendix A.5.2.3) 
 
Clarified primary safety endpoint analysis methodology (Appendix 
A.5.2.3) 
 
Clarified subgroup analysis methodology (Appendix A.6) 
 
Clarified justification for poolability of data (Appendix A.7) 
 
Clarified sensitivity analyses for missing data. Added characterization 
of TTM compliance (Appendix A.8) 
Clinical Events Committee 
(Appendix C) 
Amended CEC responsibility to review all SAEs (Appendix C) 
Data Safety Monitoring Board 
(Appendix D) 
Clarified composition of DSMB and FDA notification requirement 
(Appendix D) 

 
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Revision B – July 21, 2010 
Change 
Rationale 
Throughout document 
Relabeled TactiSys/TactiCath System to TactiCath Set 
Introduction (Sect 3) 
Augmented description of disease state (Sect 3.2) 
 
Augmented description of RF ablation (Sect 3.3) 
 
Updated description of TOCCATA data (Sect 3.7) 
Study endpoints (Sect 6) 
Added Subgroup Analyses (Sect 6.4) 
Study Design (Sect 7) 
Specified contingency analysis of sub-optimal performance 
Criteria for eligibility (Sect 8) 
Removed upper age limit (Sect 8.1) 
Study Procedures (Sect 10) 
Clarified procedures for patients with treatment failure (Sect 10.5) 
References (Sect 20) 
Added references 
Statistical Methodology 
(Appendix A) 
Added Subgroup Analyses (Appendix A.6) 
 
Added Poolability of Data (Appendix A.7) 
 
 
Revision A – May 21, 2010 
Change 
Rationale 
None 
Initial version 
 
 

 
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1. TABLE OF CONTENTS 
 
1. 
TABLE OF CONTENTS ............................................................................................. 8 
2. 
CLINICAL INVESTIGATION SYNOPSIS .............................................................. 13 
3. 
INTRODUCTION ...................................................................................................... 18 
3.1 
Device Name ..................................................................................................... 18 
3.2 
Disease State ..................................................................................................... 18 
3.3 
Radiofrequency Ablation .................................................................................. 18 
3.4 
Background ....................................................................................................... 19 
3.5 
Rationale for Development of the TactiCath Set .............................................. 19 
3.6 
Nonclinical Testing of the TactiCath Set .......................................................... 20 
3.6.1 Investigation of the TactiCath Set in an Animal Model ........................ 20 
3.7 
Prior Clinical Experience with the TactiCath Set ............................................. 20 
3.8 
Supplemental Clinical Study ............................................................................. 21 
3.9 
Continued Access Study ................................................................................... 22 
3.10 Summary ........................................................................................................... 22 
4. 
INTENDED USE AND DEVICE DESCRIPTION ................................................... 23 
4.1 
Intended Use ..................................................................................................... 23 
4.2 
Device Description ............................................................................................ 23 
4.2.1 Functionality of the TactiCath Set ........................................................ 24 
4.2.2 TactiCath Catheter ................................................................................. 24 
4.2.3 TactiSys Components ............................................................................ 24 
4.2.4 Related Components ............................................................................. 25 
5. 
STUDY PURPOSE AND OBJECTIVES .................................................................. 25 
5.1 
Study Purpose ................................................................................................... 25 
5.2 
Study Objectives ............................................................................................... 25 
5.2.1 Effectiveness ......................................................................................... 25 
5.2.2 Safety ..................................................................................................... 25 
6. 
STUDY ENDPOINTS ................................................................................................ 25 
6.1 
Primary Endpoints ............................................................................................ 25 
6.1.1 Effectiveness ......................................................................................... 25 
6.1.2 Safety ..................................................................................................... 26 
6.2 
Secondary Endpoints ........................................................................................ 26 
6.2.1 Effectiveness ......................................................................................... 26 
6.2.2 Safety ..................................................................................................... 26 

 
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6.3 
Descriptive Endpoints ....................................................................................... 26 
6.3.1 Effectiveness ......................................................................................... 26 
6.4 
Subgroup Analyses ........................................................................................... 27 
7. 
STUDY DESIGN ....................................................................................................... 27 
7.1 
Investigational Sites .......................................................................................... 28 
7.2 
Study Population ............................................................................................... 28 
7.3 
Roll-in Patient Procedures ................................................................................ 28 
7.4 
Supplemental Clinical Study Procedures .......................................................... 29 
7.5 
Continued Access Study Procedures................................................................. 29 
7.6 
Study Assessment Intervals .............................................................................. 29 
7.7 
Patient Withdrawal ............................................................................................ 30 
8. 
CRITERIA FOR ELIGIBILITY ................................................................................ 31 
8.1 
Inclusion Criteria .............................................................................................. 31 
8.2 
Exclusion Criteria ............................................................................................. 31 
9. 
SCHEDULE OF ACTIVITIES .................................................................................. 33 
10. STUDY PROCEDURES ............................................................................................ 35 
10.1 Screening and Informed Consent Procedures ................................................... 35 
10.2 Pre-treatment Procedures .................................................................................. 35 
10.2.1 Baseline Evaluations ............................................................................. 35 
10.2.2 Randomization ...................................................................................... 36 
10.2.3 Blinding to assigned treatment .............................................................. 36 
10.3 Ablation Procedure ........................................................................................... 36 
10.3.1 Peri-procedure Safety Recommendations ............................................. 38 
10.4 Pre-discharge Procedure ................................................................................... 38 
10.5 Follow-up Procedures ....................................................................................... 38 
10.5.1 7-Day Follow-up Procedure .................................................................. 39 
10.5.2 3-Month Follow-up Procedure .............................................................. 39 
10.5.3 6-Month Follow-up Procedure .............................................................. 40 
10.5.4 12-Month Follow-up Procedure ............................................................ 40 
10.5.5 Extended Follow-up Procedure ............................................................. 40 
10.5.6 Post-approval Study .............................................................................. 40 
10.6 Re-ablation Procedure ....................................................................................... 41 
10.6.1 Retreatment During the Blanking Period .............................................. 41 
10.6.2 Retreatment After the Blanking Period ................................................. 41 
10.7 Imaging for PV Stenosis ................................................................................... 41 
10.8 Ambulatory Monitoring .................................................................................... 41 

 
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10.8.1 Transtelephonic Monitoring .................................................................. 41 
10.8.2 Holter Monitoring ................................................................................. 41 
10.9 Antiarrhythmic Drug Management ................................................................... 42 
10.9.1 Blanking Period ..................................................................................... 42 
10.9.2 Effectiveness Assessment Period .......................................................... 42 
10.10 Anticoagulant Drug Management ..................................................................... 42 
10.11 Early Termination Evaluation ........................................................................... 42 
11. PATIENT BENEFITS AND RISKS .......................................................................... 43 
11.1 Potential Benefits to Study Subjects ................................................................. 43 
11.2 Potential Risks to Study Subjects ..................................................................... 43 
11.3 Clinical Events Committee ............................................................................... 43 
11.4 Clinical Risk Analysis ....................................................................................... 44 
11.4.1 Increased Risks to Subjects Posed by the Investigation ........................ 44 
11.4.2 Manner in Which Risks Will be Minimized ......................................... 44 
11.4.3 Justification for the Investigation .......................................................... 45 
11.4.4 Description of Patient Population ......................................................... 46 
11.4.5 Adverse Events ...................................................................................... 46 
11.5 Conclusion ........................................................................................................ 46 
12. ADVERSE EVENTS ................................................................................................. 46 
12.1 Definitions ......................................................................................................... 46 
12.1.1 Adverse Events ...................................................................................... 46 
12.1.2 Adverse Device Effects ......................................................................... 47 
12.1.3 Serious Adverse Events ......................................................................... 47 
12.1.4 Serious Adverse Device Effects ............................................................ 48 
12.1.5 Unanticipated Adverse Device Effects (United States sites only) ........ 48 
12.2 Primary Serious Adverse Events....................................................................... 48 
12.3 Procedure and Device Related Adverse Events ................................................ 50 
12.4 Handling and Reporting of Adverse Events ..................................................... 51 
12.4.1 European Reporting Obligations for European Investigators ............... 52 
12.4.2 United States Reporting Obligations for United States Investigators ... 52 
12.5 Early Termination or Suspension of the Clinical Investigation ........................ 52 
13. DATA QUALITY ASSURANCE.............................................................................. 52 
13.1 Case Report Forms ............................................................................................ 52 
13.2 Monitoring Procedures ...................................................................................... 53 
13.3 Data Management ............................................................................................. 53 
14. INVESTIGATIONAL PRODUCT TRACEABILITY AND RECORDING ............ 54 

 
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14.1 Device Complaints and Malfunctions ............................................................... 54 
14.2 Complaint Reporting ......................................................................................... 54 
15. ETHICS ...................................................................................................................... 54 
15.1 Declaration of Helsinki ..................................................................................... 54 
15.2 Institutional Review Board or Independent Ethics Committee Approval ........ 54 
15.3 Informed Consent .............................................................................................. 54 
15.4 Patient Identification and Confidentiality ......................................................... 55 
16. REGULATORY REQUIREMENTS ......................................................................... 55 
16.1 Compliance With Regulations Applicable to Clinical Trials............................ 55 
16.2 Competent Authority Notification .................................................................... 55 
17. CHANGES TO THE CIP OR RELATED PROCEDURES ...................................... 55 
18. DEVIATIONS FROM THE CIP ................................................................................ 56 
19. GENERAL CONSIDERATIONS .............................................................................. 56 
19.1 Discontinuation of the Study ............................................................................ 56 
19.2 Use of Information and Publication .................................................................. 56 
20. REFERENCES ........................................................................................................... 56 
21. APPENDICES ............................................................................................................ 61 
APPENDIX A Statistical Methods .......................................................................... 61 
APPENDIX B Principal Investigator....................................................................... 69 
APPENDIX C Clinical Events Committee .............................................................. 70 
APPENDIX D Data Safety Monitoring Board ........................................................ 71 
APPENDIX E Core Laboratory Services ................................................................ 72 
APPENDIX F Ambulatory Monitoring Services .................................................... 73 
APPENDIX G New York Heart Association Classes ............................................. 74 
APPENDIX H Quality of Life Survey ..................................................................... 75 
APPENDIX I List of Abbreviations ........................................................................ 76 
APPENDIX J Supplemental Clinical Study ............................................................ 78 
APPENDIX K Continued Access Study .................................................................. 85 
 
LIST OF TABLES 
Table 1 Schedule of Activities ........................................................................................... 34 
Table 2 Primary Serious Adverse Events .......................................................................... 48 
Table 3 Adverse Events Associated with Radiofrequency Ablation ................................. 50 
Table 4 Schedule of Activities for Continued Access Study ............................................. 90 
 
LIST OF FIGURES 
Figure 1 Interconnections between the TactiCath Set and related components ................ 23 

 
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Figure 2 TactiCath Quartz Set Overview .......................................................................... 80 
Figure 3 Procedure Screen Example TactiSoft v3.2 (right) and v4.3 (left) ....................... 81 
Figure 4 Procedure Screen Example TactiSoft v4.3.0.0 (left) and 4.3.1.0 (right) ............. 85 
Figure 5 “Please reset baseline” message .......................................................................... 86 
Figure 6 Settings Menu ...................................................................................................... 87 
 

 
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2. CLINICAL INVESTIGATION SYNOPSIS 
 
STUDY TITLE 
TOCCASTAR 
TactiCath® Contact Force Ablation Catheter Study for Atrial Fibrillation 
A prospective, randomized, multicenter, interventional study to evaluate the safety and 
effectiveness of the TactiCath Percutaneous Ablation Catheter for the treatment of 
symptomatic paroxysmal atrial fibrillation using contact force assisted irrigated 
radiofrequency ablation 
DEVICE 
DESCRIPTION 
The TactiCath Set includes the TactiCath Catheter and the TactiSys® Equipment. 
The TactiCath catheter is a steerable, irrigated percutaneous catheter for endocardial 
mapping and radiofrequency (RF) ablation, incorporating a tri-axial contact force 
sensor at the distal tip. The sensor allows precise measurement of the force applied by 
the catheter to the heart wall in real time. 
The TactiSys Equipment includes the Base Station and Splitter, which provide 
standard interconnection with commonly used laboratory equipment and is used for 
processing and display of data. The system displays detailed force information by 
determining the cross product of axial and lateral force components to obtain the 
resultant force vector, fully describing the contact force at the point of contact between 
the catheter and tissue surface. 
STUDY DESIGN 
TOCCASTAR is a prospective, randomized, multicenter, interventional study to 
evaluate the safety and effectiveness of the TactiCath Set for the treatment of 
symptomatic atrial fibrillation (PAF) using contact force assisted irrigated RF ablation. 
Patients undergoing elective catheter ablation for symptomatic PAF who are refractory 
or intolerant to at least one antiarrhythmic drug (Class I-IV) will be screened for 
enrollment. Patients who meet the study entry criteria and sign the patient informed 
consent form will be enrolled and treated following the 2007 Heart Rhythm Society 
(HRS)/European Heart Rhythm Association (EHRA)/European Cardiac Arrhythmia 
Society (ECAS) Expert Consensus Statement on Catheter and Surgical Ablation for 
Atrial Fibrillation. 
Eligible patients will be randomly assigned 1:1 to receive treatment with either the 
TactiCath Set or the control device (the NaviStar® ThermoCool® open irrigated RF 
ablation catheter manufactured by Biosense Webster, Inc.) Use of three-dimensional 
(3D) mapping equipment will be required in both treatment groups. Patients will be 
blinded to treatment assignment. This study aims to demonstrate non-inferiority of the 
study device to the control device for both safety and effectiveness. 
After the index procedure, patients will be followed for a total of 12 months for 
chronic effectiveness assessment, beginning with a 3-month blanking period and 
ending with a 9-month effectiveness assessment period. During the blanking period, 
patients may be prescribed a previously ineffective antiarrhythmic drug and undergo 
up to 2 repeat ablation procedures (up to 10 days prior to end of the blanking period) 
using the same device specified by the initial randomization. Patients will be evaluated 
at pre-discharge, at 7 days, at 3, 6 and 12 months post-index procedure and every 6 
months thereafter until PMA approval. 
Patients will be enrolled at up to 30 sites in the United States (US) and elsewhere. A 
maximum of 50% of patients may be enrolled outside the US.  

 
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SUPPLEMENTAL 
CLINCIAL 
STUDY 
To evaluate the comparative safety of a product evolution (TactiCath Quartz Set) 
relative to the original TactiCath Set, up to an additional 50 subjects will be enrolled in 
a supplemental phase to the Toccastar Study. These subjects will comply with the 
same protocol requirements for patient selection, treatment and follow-up as a roll-in 
subject; they will not be randomized. Data from the supplemental patients will be 
reported separately from the randomized population and will not contribute to the 
primary study endpoints. 
Please refer to Appendix J (Supplemental Clinical Study) for a description of the 
supplemental study and specific variance from the randomized protocol, where 
applicable. 
CONTINUED 
ACCESS STUDY 
Continued access to the TactiCath Quartz Set is provided during the regulatory review 
period for the Pre-Market Application. An additional 150 subjects at the original IDE 
sites may be enrolled as part of the Continued Access Study. These subjects will 
adhere to the same protocol requirements for patient selection and treatment with a 
simplified schedule of follow-up. Subjects enrolled in the Continued Access Study will 
not be randomized. Data from these subjects will be reported descriptively and 
separately from the randomized population as well as the Supplemental Clinical Study 
population. 
Please refer to Appendix K (Continued Access Study) for a description of the 
Continued Access Study and specific variance from the TOCCASTAR and 
Supplemental Clinical Study, where applicable. 
OBJECTIVES 
Effectiveness: To provide valid scientific evidence that use of the TactiCath Set is an 
effective treatment for symptomatic paroxysmal atrial fibrillation (PAF). 
Safety: To provide valid scientific evidence that use of the TactiCath Set is safe as 
measured by the incidence of early-onset serious adverse events (SAEs) when 
compared to the control device. 
PRIMARY 
ENDPOINTS 
Effectiveness 
The primary effectiveness endpoint of the study is a non-inferiority comparison of 
treatment success between the TactiCath Set and the control device as defined by both: 
 
Acute procedural success - electrical isolation of all 4 pulmonary veins (PVs), or 
in the event of a common PV, the clinical equivalent of all PVs by the end of 
index procedure 
 
Chronic success - acute procedural success and freedom from recurrence of 
symptomatic PAF, atrial flutter (AFL), and atrial tachycardia (AT) lasting longer 
than 30 seconds through 9 months of follow-up after a 3 month blanking period. 
Re-treatment for AF with ablation or the use of Class I or Class III antiarrhythmic 
drugs after the blanking period constitutes a treatment failure. 
Safety 
The primary safety endpoint is a non-inferiority comparison of device-related 
early-onset primary SAEs between the TactiCath Set and the control device occurring 
within 7 days of the index procedure or hospital discharge, whichever is later, and 
diagnosed at any time during the follow-up period. 

 
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SECONDARY 
ENDPOINTS 
Effectiveness 
The secondary effectiveness endpoints are related to the use of the contact force sensor 
and will assess procedural effectiveness superiority of the TactiCath Set over the 
control device. It is hypothesized that the use of the contact force sensor information 
will result in added procedural effectiveness through a reduction of: 
1. Number of electrically reconnected pulmonary veins following a 30-minute 
waiting period assessed by entrance block 
2. Time to achieve total PV isolation measured from initial application of RF energy 
to all target vessels isolated 
3. Total time of RF application required for full PV isolation  
Safety 
Incidence of all serious adverse events (SAEs) during the 12-month follow-up period 
DESCRIPTIVE 
ENDPOINTS 
Effectiveness 
 
Percentage of patients free of symptomatic AF episodes after treatment with 
combination therapy (previously failed AADs and/or ablation) after 12 months 
 
Percentage of patients free of symptomatic and/or asymptomatic episodes of AF 
after 12 months 
 
Freedom from AF/AFL/AT at 12 months by 24 hour Holter 
 
Total fluoroscopy time 
 
Number of RF applications 
 
Length of hospitalization 
 
Occurrence of repeat ablations (incidence and time from index procedure) 
 
Use of antiarrhythmic drugs 
 
Quality of life assessment 
 
TactiCath Set contact force data 
NUMBER OF 
PATIENTS 
A target of 300 patients (maximum 440) will be randomized. Interim analysis will be 
conducted when 50% of the patients have completed the 6-month follow-up 
procedures, and may result in a decision by the data safety monitoring board (DSMB) 
and Endosense to enroll additional patients. 
To allow for a period of familiarization with the unique features of the TactiCath Set, 
each site will be permitted to use the study device in up to 5 patients (roll-in 
population) who will not contribute data to the primary endpoint analyses. Data from 
the roll-in population will be reported separately.  
TREATMENT 
SCHEDULE 
Eligible patients will be randomly assigned 1:1 to receive treatment with one of the 
following: 
 
TactiCath Set, or 
 
Control device (the NaviStar® ThermoCool® open irrigated RF ablation catheter 
manufactured by Biosense Webster, Inc.) 
Enrolled patients will be evaluated at pre-discharge, at 7 days, at 3, 6, and 12 months 
post-index procedure and every 6 months thereafter until PMA approval. 

 
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INCLUSION 
CRITERIA 
A patient will be eligible for study participation if he/she meets the following criteria: 
1. Patient is planned to undergo a catheter ablation procedure due to symptomatic 
PAF that is refractory or intolerant to at least one Class I-IV antiarrhythmic drug 
2. Minimum of one episode of PAF greater than 30 seconds in duration within 
12 months prior to enrollment documented by 12-lead electrocardiogram (ECG), 
Holter monitor, transtelephonic event monitor, telemetry strip, or implanted 
device 
3. Minimum of 3 episodes of PAF within the preceding 12 months documented by 
patient history 
4. Patient is 18 years of age or older 
5. Patient is willing and capable of complying unassisted with the study protocol 
requirements including all specified follow-up visits 
6. Patient provides written informed consent prior to enrollment in the study 
EXCLUSION 
CRITERIA 
A patient will be excluded from the study if he/she meets any of the following criteria: 
1. Persistent or long-standing persistent atrial fibrillation (AF) 
2. Patient has had 4 or more cardioversions in the last 12 months 
3. Active systemic infection 
4. Presence of implantable cardiac defibrillator (ICD) 
5. Arrhythmia due to reversible causes including thyroid disorders, acute alcohol 
intoxication, and other major surgical procedures in the preceding 3 months 
6. Myocardial infarction (MI), acute coronary syndrome, percutaneous coronary 
intervention (PCI), or valve or coronary bypass grafting surgery within preceding 
3 months 
7. Left atrial diameter > 5.0 cm 
8. Left ventricular ejection fraction < 35% 
9. New York Heart Association (NYHA) class III or IV 
10. Previous left atrial ablation procedure, either surgical or catheter ablation 
11. Patient has had a left atrial surgical procedure or incision with resulting scar 
12. Previous tricuspid or mitral valve replacement or repair 
13. Heart disease in which corrective surgery is anticipated within 6 months 
14. Bleeding diathesis or suspected pro coagulant state 
15. Contraindication to long term antithromboembolic therapy 
16. Presence of condition that precludes appropriate vascular access 
17. Renal failure requiring dialysis 
18. Known sensitivity to contrast media (if needed during the procedure) that cannot 
be controlled with pre-medication 
19. Contraindication to computed tomography and magnetic resonance angiography 
20. Severe 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 severe chronic symptoms 
21. Positive pregnancy test results for female patient of childbearing potential 
22. Patient has other anatomic or co morbid conditions that, in the investigator’s 
opinion, could limit the patient’s ability to participate in the study or to comply 
with follow up requirements, or impact the scientific soundness of the study 
results 
23. Patient is currently participating in another clinical trial or has participated in a 
clinical trial within 30 days prior to screening that may interfere with this study 
24. Patient is unlikely to survive the protocol follow up period of 12 months 
 

 
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CRITERIA FOR 
WITHDRAWAL 
All patients are free to withdraw from participation in this study at any time, for any 
reason, and without prejudice. Patients may be withdrawn from the study when they 
request early discontinuation or are lost to follow-up. 
The clinical investigator may terminate a patient from the study at any time for lack of 
therapeutic effect that is intolerable to the patient, or otherwise considered 
unacceptable, for intolerable or unacceptable AEs, intercurrent illness, noncompliance 
with study procedures, administrative reasons, or in the clinical investigator’s opinion, 
to protect the patient’s best interest. 
ENROLLMENT 
PERIOD 
Enrollment began in the first quarter of 2011 (Q1 2011) and is expected to be complete 
by approximately Q1 2012. 
STUDY 
DURATION 
The total study duration is approximately 24 months: assuming 12 months for patient 
enrollment and followed by a 12-month follow-up period. 
INVESTIGATIVE 
SITES AND 
COUNTRIES 
Up to 30 sites in the US and elsewhere may participate in the study. 
 
 

 
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3. INTRODUCTION 
3.1 
Device Name 
The device under clinical investigation is the Endosense TactiCath Set (TactiCath Catheter 
and TactiSys Equipment). 
3.2 
Disease State 
With a high risk for stroke at 1.6% per year and a primary prevalence of 6 million people, 
atrial fibrillation (AF) is a one of the biggest treatment challenges for cardiologists today.2-4 
AF is one of a diverse group of arrhythmias collectively described as supra-ventricular 
tachyarrhythmia (SVT). In SVT, the trigger originates in the atrium or the atrium is part of 
the re-entry mechanism for triggering or maintaining the arrhythmia. SVTs vary considerably 
in their rate and regularity, their clinical manifestations, and the setting in which they occur. 
These arrhythmias are characteristically abrupt in onset and termination and are often seen in 
patients who do not have evidence of organic heart disease. Although these disturbances in 
rhythm are generally not malignant in the short-term, in patients with organic heart disease a 
rapid atrial rhythm may produce significant hemodynamic complications. In some patients 
with pre-excitation syndromes combined with an anterograde accessory pathway, there is 
also a risk of sudden death. 
SVTs are usually divided into the following 3 groups: 
 Supra-ventricular tachycardias (i.e., atrial tachycardia [AT], sino-atrial node re-entry, 
intra-atrial re-entry, atrioventricular reentrant tachycardias [Wolff-Parkinson-White 
syndrome], and atrioventricular nodal reentrant tachycardia) 
 Atrial flutter (AFL) 
 Atrial fibrillation (AF) 
 
Long-term outcomes for symptomatic AF patients treated exclusively with drugs remains 
poor.5,6 Treatment of AF using RF ablation or surgery has become increasingly important. 
Various techniques are being proposed that use ablation in the left atrium.4 
 
3.3 
Radiofrequency Ablation 
Radiofrequency (RF) catheter ablation is a minimally invasive procedure commonly used for 
more than 20 years to treat most of the recurrent supra-ventricular tachyarrhythmias.1-3 
Recent advances in the underlying science and technology of ablation for AF have identified 
the benefits of irrigation and temperature monitoring to control for char formation and reduce 
embolic risk. A steerable catheter tip provides additional flexibility for catheter placement. 
These features have been incorporated in the design of the TactiCath catheter. 

 
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With the exception of AF, supra-ventricular tachyarrhythmias can be treated by ablation in 
the right atrium only. For the treatment of AF, an intervention in the left atrium is required. 
3.4 
Background 
The 2006 American College of Cardiology (ACC)/American Heart Association 
(AHA)/European Society of Cardiology (ESC) guidelines for the treatment of AF 
recommend catheter ablation as a second-line therapy after a patient has been shown to be 
refractory or intolerant to at least one Class I or III antiarrhythmic medication.2 The 2007 
Heart Rhythm Society (HRS)/European Heart Rhythm Association (EHRA)/European 
Cardiac Arrhythmia Society (ECAS) Expert Consensus Statement on Catheter and Surgical 
Ablation of Atrial Fibrillation reiterates this recommendation.3 The 2009 Comparative 
Effectiveness Review of Radiofrequency Catheter Ablation published by the US Department 
of Health and Human Services further describes the risks and benefits associated with RF 
ablation for PAF.27 
Circumferential electrical isolation of the entire pulmonary vein (PV) musculature is now 
common practice for patients with paroxysmal atrial fibrillation (PAF) in whom one or more 
antiarrhythmic agents have failed. This procedure, also known as PV isolation, seeks to block 
the conduction of arrhythmia triggers originating in PV foci and has become the accepted 
approach for AF ablation worldwide. The risks for this procedure are known and include 
complications such as tamponade, stroke, severe PV stenosis, esophageal fistula, major 
bleeding requiring surgery or transfusion, and death. Based on voluntary international 
surveys (self-reported results), the currently reported complication rate is 5.9%, with a fatal 
outcome in 0.1% of patients.7, 8 
3.5 
Rationale for Development of the TactiCath Set 
Recent nonclinical research has shown that sufficient contact force between the ablation tip 
and target tissue is an important determinant of effective lesion creation, although higher 
contact force increases the risk for complications such as steam pop formation, thrombus 
formation, and perforations.9-20 Applying the correct contact force during catheter ablation is 
important. Insufficient contact force may result in an ineffective procedure as the lesion 
remains superficial and does not achieve the required lesion depth, thereby permitting 
electrical reconnection and a resumption of symptoms. Conversely, excessive contact force 
may result in complications such as perforation of the heart wall, steam pop formation, or 
esophageal injury. Currently, electrophysiologists generally rely on subjective interpretation 
of electrocardiograms (ECGs), fluoroscopic images and handling cues to determine how 
much force to apply at each lesion site. Establishing a stable contact force between the 
catheter and the endocardial surface remains one of the key challenges in the catheter 
ablation procedure. 
To address this need, Endosense has developed a novel contact force sensor that is embedded 
in the TactiCath catheter that allows measurement of the tip to tissue contact force during the 
RF ablation procedure. With the TactiCath Set, the physician is expected to be able to better 
position the ablation catheter by monitoring real-time contact force information during 

 
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mapping and ablation. It is hypothesized that lesions created with an optimal catheter contact 
force will improve long-term freedom from recurrence in patients. 
The topic of contact force sensing during ablation is gaining international attention at an 
increasing rate as evidenced by the recent 15th Annual Boston AF Symposium (14 –
16 Jan 2010) at which a symposium session dedicated to this topic was presented.21 The 
session made clear that in addition to Endosense, other device companies are developing 
contact force assisted RF ablation catheters to address this need.22 To date, Endosense is the 
only company that has conducted a multi-center clinical study of an ablation catheter with an 
integrated force sensor, the TOCCATA study23 (Section 3.7).  
3.6 
Nonclinical Testing of the TactiCath Set 
Comprehensive nonclinical testing of the TactiCath Set has been performed to validate and 
verify the device design in support of the clinical study. Nonclinical testing consisted of 
functional and procedural testing in both bench and animal laboratory settings. 
Additional animal studies unrelated to the Investigational Device Exemption (IDE) 
submission were previously conducted to characterize parameters for the safe use of the 
TactiCath Set including evaluations of perforation force, correlation of force with lesion size, 
and correlation of force with esophageal injury.9-14,16,17,20 
3.6.1 Investigation of the TactiCath Set in an Animal Model 
A study approved by the Institutional Animal Care and Use Committee (IACUC) was 
performed in GLP-like conditions to assess the safety and effectiveness of the TactiCath Set. 
Various parameters were assessed in a series of 8 animals including packaging and sterility, 
catheter deployment and steerability, intracardiac signal quality, compatibility with cath lab 
equipment, irrigated RF ablation success, force sensor functionality during mapping and 
ablation and visualization of contact force. The TactiCath system performed to specification 
while mapping all 4 chambers and delivering lesions to isolate 2 targeted pulmonary veins in 
each animal which remained isolated after a minimum of one hour. All animals survived the 
procedure with no significant adverse events such as PV stenosis, esophageal injury, cardiac 
tamponade, respiratory distress or uncontrollable bleeding. 
3.7 
Prior Clinical Experience with the TactiCath Set 
The TactiCath Set was extensively studied in Europe during the TOCCATA study, which 
began enrollments in late 2008 and concluded follow-up in early 2010.23 In this 
non-randomized, European, safety, performance and preliminary effectiveness study, 
21 operators used the TactiCath Set to treat a total of 76 patients (34 AF, 27 AFL, and 15 
other supra-ventricular tachycardias). Patients were followed for one year. 
The primary safety endpoints of the study were met. The study characterized, for the first 
time, the wide range of contact forces that are typical in the course of an atrial ablation 
procedure. Results from the TOCCATA study were successfully submitted in support of an 
application for CE mark of approval granted in May 2009. 

 
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Data from the long-term follow-up of patients enrolled in TOCCATA recently presented at 
the Cardiostim 2010 meeting29 describe a correlation between average contact force applied 
during ablation and freedom from arrhythmia recurrence at 6 months. AF Patients treated 
with RF ablation whose arrhythmias recurred experienced significantly lower average 
contact force during ablation than patients without recurrence (14.9g vs. 19.0g, p=0.039).  
Unpublished data presented at this meeting updated these results to demonstrate an even 
more significant difference at 12 months (14.5g vs. 19.5g, p=0.01). These results suggest that 
a subgroup analysis may be relevant in the TOCCASTAR study to separately report on 
outcomes for patients with higher average contact force during ablation. 
3.8 
Supplemental Clinical Study 
The initial randomized phase of the TOCCASTAR Study began enrollment in January of 
2011 and has completed enrollment as of June 2012. The study data is expected to be 
submitted in an original PMA in Q3 of 2013. 
In November of 2013, an IDE supplement will be submitted to request the further enrollment 
of up to 50 non-randomized patients using an evolutionary version of the study device known 
as the TactiCath Quartz Set. This device received CE mark in May of 2012 and has been 
used in a commercial setting outside the US since June of 2012. Prior to first clinical use in 
the US, a comprehensive verification and validation study will confirm the operation and 
robustness of the new device. 
The main objective of the Supplemental Clinical Study will be to provide confirmatory 
evidence regarding the acute safety and effectiveness of the TactiCath Quartz Set in patients 
with symptomatic PAF. In principle, the TactiCath Quartz Set will provide the same 
therapeutic and diagnostic functionality to the operator during use as the TactiCath Set. The 
risks and benefits will also be the same. The new device will be evaluated in an identical 
patient population (inclusion and exclusion criteria) using the same procedural methodology 
as the randomized study. 
Given the similarities in patient populations, device functionality, and procedural testing 
requirements, the acute procedural and 30 day safety data from the TactiCath Quartz Set may 
be compared with data from the TactiCath Set. Therefore, a minimum of 30 days of follow-
up data on 50 subjects will be submitted for FDA review, plus any additional follow- up data 
available at the time of submission. Subjects enrolled in the supplemental study will comply 
with the same extended follow-up requirements from the randomized study (every 6 months 
until PMA approval) that will provide additional safety and effectiveness data from the post-
assessment period through PMA approval.  
Sites that agree to participate in the Supplemental Clinical Study will be required to obtain 
IRB approval of the Clinical Investigation Plan, Version F and the corresponding Patient 
Informed Consent. Subjects previously enrolled in the TOCCASTAR Study will not be 
affected by the protocol revision, however re-consenting of these subjects is at the discretion 
of the participating site. 

 
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Conduct of the Supplemental Clinical Study will conform to the initial randomized 
TOCCASTAR Study except where indicated. Details regarding the Supplemental Clinical 
Study, especially with respect to differences from the randomized study, are provided in 
APPENDIX J. 
 
3.9 
Continued Access Study 
The last subject enrollment in the TOCCASTAR Study occurred in June 2013. This includes 
randomized, roll-in and Supplemental Clinical Study subjects. The TOCCASTAR Clinical 
Study Report was received by FDA on 29 November 2013 thus completing the PMA 
submission. The TOCCASTAR study submission presented preliminary evidence that the 
TactiCath Quartz Set is likely to be effective and that no significant safety concerns have 
been identified for the proposed indication of treatment of drug refractory symptomatic 
paroxysmal atrial fibrillation.  
In January 2014, an IDE supplement will be submitted for continued access to TactiCath 
Quartz Set for existing investigators during the period of regulatory review of the 
TOCCASTAR PMA submission. The request will be for enrollment of up to 150 non-
randomized patients that will be treated with the TactiCath Quartz Set under the same 
indication to provide confirmatory evidence of safety and effectiveness.  The previous 
TOCCASTAR clinical protocol (Version F) and Patient Informed Consent will be modified 
to reflect the addition of the Continued Access Study (Version H). The devices used in the 
Continued Access Study will be the same as were used during the Supplemental Clinical 
Study. 
Sites that agree to participate in the Continued Access Study will be required to obtain IRB 
approval of Version H of the Protocol and the corresponding Patient Informed Consent. 
Subjects already enrolled in the TOCCASTAR Study and the Supplemental Study will not be 
affected by the protocol revision, however re-consenting of existing subjects is at the 
discretion of the participating site. 
Conduct of the Continued Access Study will conform to the initial randomized 
TOCCASTAR Study except where indicated. Details regarding the Continued Access Study 
are provided in APPENDIX K. 
3.10 Summary 
Based on these considerations, the Endosense TactiCath Set (TactiCath Catheter and 
TactiSys Equipment) may be a valuable addition to existing technology available to treat 
PAF and should be further studied in an IDE clinical trial. 

 
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4. INTENDED USE AND DEVICE DESCRIPTION 
4.1 
Intended Use 
The TactiCath Set is intended to be used during ablation of PAF to perform PV isolation and 
to create other lesions as needed to safely and effectively eliminate undesirable arrhythmia 
triggers and prevent the recurrence of arrhythmia. The embedded contact force sensor 
provides additional diagnostic information during catheter manipulation to aid in the creation 
of optimal lesions. 
4.2 
Device Description 
The TactiCath Set24 includes the TactiCath Catheter and the TactiSys Equipment, which are 
described below and are illustrated in Figure 1. 
Figure 1 Interconnections between the TactiCath Set and related components 
 
 

 
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4.2.1 Functionality of the TactiCath Set 
The TactiCath Set has been designed to perform the following functions in the setting of a 
clinical electrophysiology laboratory: 
 Transmitting cardiac signals for monitoring 
 Transmitting pacing signals for electrophysiological study 
 Transmitting RF energy to the heart wall 
 Objective real time measurement and visualization of the contact force between the catheter 
tip and the endocardial surface 
 Storing and reporting of procedural data collected from the contact force sensor and 
adjunctive equipment 
4.2.2 TactiCath Catheter 
The Endosense TactiCath Contact Force Ablation Catheter (version number PN-003 165) is a 
multi-electrode irrigated catheter with a deflectable tip designed to allow 
electrophysiological mapping of the heart and, when connected to an RF generator, to 
transmit radiofrequency current to the catheter tip electrode for the purpose of ablation. 
RF generators to be used with TactiCath must be compatible with the functional requirements 
of TactiCath as specified in the TactiSys User Manual and part of a commercially approved 
system in the US for performing cardiac ablations. 
The catheter tip has an integrated force sensor that, when used with the TactiSys Equipment, 
allows real-time visualization of the catheter tip contact force. 
The TactiCath catheter has the same size as and is designed to be similar to other 
state-of-the-art open tip irrigated RF ablation catheters. The TactiCath catheter can be 
integrated into an existing electrophysiology lab and connected with an RF generator, 
cooling pump, and three-dimensional (3D) imaging systems. 
4.2.3 TactiSys Components 
The TactiSys Equipment includes the Base Station and Splitter, which provide standard 
interconnection with commonly used laboratory equipment for data processing and display. 
The system displays detailed force information by determining the cross product of axial and 
lateral force components to obtain the resultant force vector, fully describing the force at the 
point of contact between the catheter and tissue surface. 
 Base Station 
The Base Station is the principal signal processing unit of the TactiCath Set. It hosts the main 
piece of software, TactiSoft, which collects the force sensing signal from the catheter tip and 
computes the force values that are shown on the display. 

 
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 Splitter 
The Splitter is the interface between the catheter and the Base Station, and between the 
catheter and the RF generator. 
The Splitter is compatible with the Endosense TactiCath Catheter PN-003 165. 
4.2.4 Related Components 
The following related components are required to operate the TactiCath Set but are not part 
of the TactiCath Set: 
 RF generator 
 Volumetric infusion pump 
 Video display 
5. STUDY PURPOSE AND OBJECTIVES 
5.1 
Study Purpose 
The purpose of this study is to evaluate the safety and effectiveness of the TactiCath Set 
when used to treat PAF when compared to an approved control device. Prospective contact 
force data will be collected and analyzed to evaluate the importance of real-time contact 
force sensing during the RF ablation procedure. 
5.2 
Study Objectives 
5.2.1 Effectiveness 
To provide valid scientific evidence that use of the TactiCath Set is an effective treatment for 
symptomatic PAF. 
5.2.2 Safety 
To provide valid scientific evidence that use of the TactiCath Set is safe as measured by the 
incidence of early-onset serious adverse events (SAEs) when compared to the control device. 
6. STUDY ENDPOINTS 
The following study endpoints will be evaluated for all patients who satisfy entry criteria, are 
randomized, and are subsequently enrolled into the study.  
6.1 
Primary Endpoints 
6.1.1 Effectiveness 
The primary effectiveness endpoint of the study is a non-inferiority comparison of treatment 
success between the TactiCath Set and the control device as defined by both: 

 
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 Acute procedural success - electrical isolation of all 4 PVs, or in the event of a common PV, 
the clinical equivalent of all PVs, by the end of index procedure (with the device specified by 
the randomization arm). 
 Chronic success - acute procedural success and freedom from recurrence of symptomatic AF, 
AFL, and AT lasting longer than 30 seconds through 9 months of follow-up after a 3 month 
blanking period. Re-treatment for AF with ablation or the use of Class I or Class III 
antiarrhythmic drugs after the blanking period constitute a treatment failure. 
6.1.2 Safety 
The primary safety endpoint is a non-inferiority comparison of device-related early-onset 
primary SAEs between the TactiCath Set and the control device occurring within 7 days of 
the index procedure or hospital discharge, whichever is later, and diagnosed at any time 
during the follow-up period. PSAEs that meet the severity criteria described in Table 2 will 
contribute to the primary safety endpoint only in patients in whom a study device (TactiCath 
or control) has been introduced.  
Hospitalizations solely for arrhythmia recurrence (without coexisting conditions such as 
thromboembolism, worsening heart failure, etc.) will not be considered primary SAEs. 
6.2 
Secondary Endpoints 
6.2.1 Effectiveness 
The secondary effectiveness endpoints are related to the use of the contact force sensor and 
will assess procedural effectiveness superiority of the TactiCath Set over the control device 
using a hierarchical closed test procedure. It is hypothesized that the use of the contact force 
sensor information will result in added procedural effectiveness through a reduction of: 
1. Number of electrically reconnected pulmonary veins following a 30-minute waiting 
period assessed by entrance block 
2. Time to achieve total PV isolation measured from initial application of RF energy to all 
target vessels isolated 
3. Total time of RF application required for full PV isolation 
6.2.2 Safety 
The secondary safety endpoint will evaluate the incidence of all serious adverse events 
during the 12-month follow-up period. 
6.3 
Descriptive Endpoints 
6.3.1 Effectiveness 
The following parameters will be reported as observational endpoints: 
 Percentage of patients free of symptomatic AF episodes after treatment with combination 
therapy (previously failed AADs and/or ablation) after 12 months 

 
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 Percentage of patients free of symptomatic and/or asymptomatic episodes of AF after 12 
months 
 Freedom from AF/AFL/AT at 12 months by 24 hour Holter 
 Total fluoroscopy time 
 Number of RF applications 
 Length of hospitalization 
 Occurrence of repeat ablations (incidence and time from index procedure) 
 Use of antiarrhythmic drugs 
 Quality of life assessment 
 TactiCath Set contact force data  
o Force distribution – distribution of forces employed during ablation per patient procedure 
o Contact force (CF) parameters during ablation including: number of ablations, average 
CF, standard deviation CF, minimum average CF, maximum average CF, 5th percentile 
average CF, 95th percentile average CF – correlate CF parameters with recurrence, time 
to PV isolation, acute success, and other procedural efficiency parameters 
o Force Time Integral (FTI) – correlate FTI with recurrence, time to PV isolation, acute 
success, and other procedural efficiency parameters 
o Trends – comparison of force data from the first third treated patients with the last third 
treated patients across and within centers and per operator 
 
6.4 
Subgroup Analyses 
The primary and secondary safety and effectiveness endpoints will be compared (via 
superiority testing) between the control group and a subgroup of patients from the TactiCath 
arm whose average contact force during ablation was ≥ 20 g. 
 
7. STUDY DESIGN 
TOCCASTAR is a prospective, randomized, multicenter, interventional study to evaluate the 
safety and effectiveness of the TactiCath Set for the treatment of symptomatic PAF using 
contact force assisted irrigated RF ablation. 
Patients undergoing elective catheter ablation for symptomatic PAF who are refractory or 
intolerant to at least one antiarrhythmic drug (Class I-IV) will be enrolled. Patients who meet 
the study entry criteria and sign the patient informed consent form will be enrolled and 
treated following the HRS/EHRA/ECAS Expert Consensus Statement on Catheter and 
Surgical Ablation for Atrial Fibrillation.3 
Eligible patients will be randomly assigned 1:1 to receive treatment with either the TactiCath 
Set or the control device (the NaviStar® ThermoCool® open irrigated RF ablation catheter 
manufactured by Biosense Webster, Inc.) Use of 3D mapping equipment will be required in 
both treatment groups. Patients will be blinded to treatment assignment. This study aims to 

 
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demonstrate non-inferiority of the study device to the control device for both safety and 
effectiveness. 
 
If chronic success is determined to be less than 40% for either the treatment group or the 
control group, additional exploratory analyses focused on explaining the suboptimal results 
will be performed. 
7.1 
Investigational Sites 
Up to 30 sites in the United States and elsewhere will be invited to participate in the study. 
Investigators will be selected from the electrophysiology specialty and will agree to comply 
with all aspects of the investigational protocol. Use of adjunctive equipment will be limited 
to devices approved in the US unless approved for use as part of a sub-study. 
7.2 
Study Population 
The trial will be conducted in 300 randomized patients with symptomatic PAF (150 patients 
per treatment group) who are refractory or intolerant to at least one antiarrhythmic drug 
(Class I-IV). A maximum of 50% of patients may be enrolled outside the US. 
Eligible patients will be included in the study as they become available. Treatments will be 
randomly assigned (Section 10.2.2). Patients will remain blinded to their treatment 
assignment throughout the study (Section 10.2.3). 
Subjects who sign an informed consent and satisfy all pre-operative entry criteria will be 
considered for randomization and treatment. Consented subjects who do not satisfy entry 
criteria are screen failures and will not receive treatment under this protocol. Those screen 
failures will conclude their participation in the study without further follow-up or data 
collection activities. 
Subjects in whom PVI is contraindicated based on an intra-operative finding such as 
AVRT/AVNRT will be excluded from the primary endpoint analyses. These subjects will be 
followed for safety only. Data from these subjects will be reported separately. 
7.3 
Roll-in Patient Procedures 
To allow for a period of familiarization with the unique features of the TactiCath Set, each 
site will be permitted to use the study device in up to 5 patients that are not randomized in 
the study, up to 100 total roll-in patients. The roll-in patient population will be screened, 
consented, and treated with the TactiCath Set, and followed per protocol for 12 months.  
Data from patients who participate in roll-in procedures will be excluded from the primary 
endpoint analyses. Data from the roll-in population will be reported separately in the study 
report. 

 
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7.4 
Supplemental Clinical Study Procedures 
As a supplement to the original TOCCSTAR Study, up to 50 additional non-randomized 
patients will be enrolled in a Supplemental Clinical Study. For the purposes of screening, 
consent, treatment and follow-up, these subjects will be treated identically to the roll-in 
patient population (with the exception of CT/MR scans that are no longer required). Details 
regarding the Supplemental Clinical Study procedures are provided in APPENDIX J. 
7.5 
Continued Access Study Procedures 
During the Continued Access phase of the study, up to 150 additional non-randomized 
patients will be enrolled. These subjects must meet the same enrollment criteria, undergo the 
same consent process, same treatment and follow-up as the initial randomized TOCCASTAR 
Study with the following exceptions: 
 CT/MR scans are recommended but not required 
 Ambulatory monitoring with TTM is no longer required and is replaced with 
additional instances of Holter monitoring at 3, 6, and 12 months 
Details regarding study procedures during the Continued Access Study are provided in 
Appendix K. 
7.6 
Study Assessment Intervals 
For the purpose of assessing study endpoints, patients will be followed for a total of 
12 months after the index procedure beginning with a 3-month blanking period and ending 
with a 9-month effectiveness assessment period. During the blanking period, patients may be 
prescribed a previously ineffective antiarrhythmic drug and undergo up to 2 repeat ablation 
procedures (up to 10 days prior to end of the blanking period) using the device specified by 
the initial randomization. Enrolled patients will be evaluated according to the 
HRS/EHRA/ECAS Expert Consensus Statement3 at pre-discharge, at 7 days, and at 3, 6, and 
12 months post-index procedure. After the 12-month follow-up, patients will be contacted 
periodically (every 6 months until the post market approval (PMA) is granted, and if 
approved, thereafter according to post-approval requirements) to assess general health and 
well-being. 
Assuming approximately 12 months for patient enrollment and a 12-month follow-up period 
per patient (including a 3-month blanking period), this study is expected to require 
approximately 24 months to complete. 
When FDA approves a device for commercial use in the United States, they often ask that 
patients in the clinical trial agree to continue monitoring for several more years to confirm 
the long-term results of the study. If this occurs, the study will extend for up to 5 years from 
the time of the initial procedure. FDA has stipulated that informed consent will include 
participation in the Toccastar study as well as a possible post-approval study that may be 
specified by FDA at a later date. 

 
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7.7 
Patient Withdrawal 
All patients are free to withdraw from participation in this study at any time, for any reason, 
and without prejudice.  
Patients may be withdrawn from the study for any of the following reasons: 
 Patient requests early discontinuation 
 Patient is lost to follow-up 
The clinical investigator may terminate a patient from the study at any time for lack of 
therapeutic effect that is intolerable to the patient, or otherwise considered unacceptable, for 
intolerable or unacceptable AEs, intercurrent illness, noncompliance with study procedures, 
administrative reasons, or in the clinical investigator’s opinion, to protect the patient’s best 
interest. 
Patients who request early discontinuation will be considered as having withdrawn consent 
only after they have signed the Withdrawal of Consent Form. Patients who withdraw consent 
will receive standard of care treatment. 
The clinical investigator will make every effort to collect information about patients who are 
lost to follow-up. 
If a patient is withdrawn before completing the study, the reason for withdrawal (assuming 
the patient is willing and able to share this information) will be entered on the Study 
Completion Form. Patients who withdraw before completing the study will be followed only 
through the date of their withdrawal. 
In addition, any comments (spontaneous or elicited) or complaints made by the patient or 
physician caring for the patient but not involved in the investigation will be documented on 
the eCRF.  

 
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8. CRITERIA FOR ELIGIBILITY 
8.1 
Inclusion Criteria 
A patient will be eligible for study participation if he/she meets the following criteria: 
1. Patient is planned to undergo a catheter ablation procedure due to symptomatic PAF that is 
refractory or intolerant to at least one Class I-IV antiarrhythmic drug 
2. Minimum of one episode of PAF greater than 30 seconds in duration within 12 months prior 
to enrollment documented by 12-lead ECG, Holter monitor, transtelephonic event monitor, 
telemetry strip, or implanted device 
3. Minimum of 3 episodes of PAF within the preceding 12 months documented by patient 
history 
4. Patient is 18 years of age or older  
5. Patient is willing and capable of complying unassisted with the study protocol requirements 
including all specified follow-up visits 
6. Patient provides written informed consent prior to enrollment in the study 
8.2 
Exclusion Criteria 
A patient will be excluded from the study if he/she meets any of the following criteria: 
1. Persistent or long-standing persistent AF  
2. Patient has had 4 or more cardioversions in the last 12 months  
3. Active systemic infection 
4. Presence of implantable cardiac defibrillator (ICD) 
5. Arrhythmia due to reversible causes including thyroid disorders, acute alcohol intoxication, 
and other major surgical procedures in the preceding 3 months 
6. Myocardial infarction (MI), acute coronary syndrome, percutaneous coronary intervention 
(PCI), or valve or coronary bypass grafting surgery within the preceding 3 months 
7. Left atrial diameter > 5.0 cm 
8. Left ventricular ejection fraction < 35% 
9. New York Heart Association (NYHA) class III or IV (Appendix G) 
10. Previous left atrial ablation procedure, either surgical or catheter ablation 
11. Patient has had a left atrial surgical procedure or incision with resulting scar 
12. Previous tricuspid or mitral valve replacement or repair 
13. Heart disease in which corrective surgery is anticipated within 12 months 

 
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14. Bleeding diathesis or suspected pro-coagulant state 
15. Contraindication to long-term antithromboembolic therapy  
16. Presence of condition that precludes appropriate vascular access 
17. Renal failure requiring dialysis 
18. Known sensitivity to contrast media (if needed during the procedure) that cannot be 
controlled with pre-medication 
19. Contraindication to computed tomography and magnetic resonance angiography procedure 
20. Severe 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 severe chronic symptoms 
21. Positive pregnancy test results for female patient of childbearing potential 
22. Patient has other anatomic or co-morbid conditions that, in the investigator’s opinion, could 
limit the patient’s ability to participate in the study or to comply with follow-up 
requirements, or impact the scientific soundness of the study results 
23. Patient is currently participating in another clinical trial or has participated in a clinical trial 
within 30 days prior to screening that may interfere with this study 
24. Patient is unlikely to survive the protocol follow-up period of 12 months 

 
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9. SCHEDULE OF ACTIVITIES 
The study began in the first quarter of 2011 (Q1 2011), when the first patient was enrolled. 
Recruitment of all patients, including roll-in patients, was completed in Q1 2012.  
Evaluation of patients enrolled in this study will include all tests and procedures listed in the 
Schedule of Activities (Table 1). See Appendix K for the study details for subjects enrolled 
into the Continued Access Protocol. 

 
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Table 1 Schedule of Activities 
 
Baseline 
Procedure 
Pre-
discharge 
7 days 
± 2 days 
Telephone 
3 months 
± 2 weeks 
6 months 
± 3 weeks 
12 months 
± 3 weeks 
Extended 
every 6 mos 
± 4 weeks 
Informed consent 
X 
 
 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
Documentation of PAF episodes 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Thyroid and renal function (standard practice) 
X 
 
 
 
 
 
 
 
PT/PTT or INR 
X 
 
X 
 
 
 
 
 
Physical examination,vital signs, height, weighta 
X 
 
X 
 
X 
X 
X 
 
Pregnancy test (women of childbearing potential) 
X 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
X 
 
X 
X 
X 
 
Cardiac medications 
X 
 
X 
X 
X 
X 
X 
 
NYHA functional class 
X 
 
 
 
X 
X 
X 
 
Quality of life survey 
X 
 
 
 
 
 
X 
X 
Randomization 
X 
 
 
 
 
 
 
 
Activated clotting time  
 
X 
 
 
 
 
 
 
Ablation procedure data 
 
X 
 
 
 
 
 
 
Force Sensing data (TactiCath treatment group) 
 
X 
 
 
 
 
 
 
Arrhythmia events 
X 
 
X 
X 
X 
X 
X 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
Xf 
Protocol deviation 
X 
X 
X 
X 
X 
X 
X 
 
TEE (ICE)b 
X 
(X) 
 
 
 
 
 
 
TTE (recommended)c 
X 
 
(X) 
 
 
 
 
 
CT or MRI scand 
X 
 
 
 
X 
 
 
 
Transtelephonic monitoringe 
 
 
 
 
X 
X 
X 
 
Holter monitoring 
 
 
 
 
 
 
X 
 
Arrhythmia history 
 
 
 
 
 
 
 
X 
Abbreviations: CT = computed tomography; ECG = electrocardiogram; INR = international normalized ratio; MRI = magnetic resonance imaging; NYHA = New 
York Heart Association; PAF = paroxysmal atrial fibrillation; PT = prothrombin time; PTT = partial thromboplastin time; TEE = trans-esophageal echocardiography; 
ICE = intra-cardiac echocardiography. NOTES: a.Weight and height will be assessed at baseline only. b.TEE within 24 hrs or ICE at time of procedure to exclude 
atrial thrombus. c.TTE within 6 mos to measure left atrial dimension. Recommended within 24 hrs post procedure to exclude pericardial effusion. d.Not required for 
supplemental study subjects. If evidence of stenosis is seen at 3 mos, the investigator may prescribe additional serial scans. e.TTMs weekly for months 4 and 5, 
monthly for months 6-12, and as needed to document symptomatic episodes. f.survival and hospitalizations only. 

 
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10. STUDY PROCEDURES 
Cardiac medications and protocol deviations will be recorded from the time of signing the 
informed consent through the date of study completion or withdrawal. 
10.1 Screening and Informed Consent Procedures 
When a suitable candidate requiring ablation for PAF presents for consideration for 
enrollment in the study, the investigator will explain the potential risks and benefits of 
participation to the patient. Patients will be provided with a copy of the informed consent for 
review and will be given ample opportunity to read and pose questions they may have about 
the study. If after review, the patient agrees to participate, the informed consent will be 
signed by the patient and recorded on a screening/enrollment log. If a patient subsequently 
fails to meet eligibility criteria, they will be considered a screening failure and may receive 
standard of care for their condition outside of the study. 
10.2 Pre-treatment Procedures 
10.2.1 Baseline Evaluations 
The following baseline evaluations will be performed for eligible patients within 30 days (or 
as indicated) prior to the planned treatment procedure. 
1. Written informed consent 
2. Evaluation of inclusion/exclusion criteria 
3. Documentation of 3 symptomatic PAF episodes and one PAF episode > 30 seconds 
evidenced by ECG tracing (any source) within 12 months 
4. Medical history, including demographics, arrhythmia diagnosis, cardiovascular risk factors, 
cardiac medication 
5. Arrhythmia history - patient should be refractory or intolerant to at least one Class I-IV 
antiarrhythmic drug 
6. General physical examination including vital signs, height, and weight 
7. Prothrombin time (PT)/ partial thromboplastin time (PTT) or international normalized ratio 
(INR) following standard clinical practice 
8. Blood tests of thyroid and renal function following standard clinical practice 
9. 12-lead ECG 
10. Determination of the NYHA functional class 
11. Quality of life assessment  

 
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12. Assessment of atrial thrombus. Either via trans-esophageal echocardiography (TEE) within a 
period of 24 hours prior to the treatment procedure or, intracardiac echo (ICE) at the time of 
the procedure in patients currently in normal sinus rhythm with no history of cerebrovascular 
accident. 
13. Location, morphology, and dimensions of PVs using computed tomography (CT) scan or 
magnetic resonance imaging (MRI) within 60 days (recommended but not required for 
Supplemental Clinical Study and Continued Access Study subjects) 
14. Assessment of left atrial diameter via trans-thoracic echocardiography (TTE) within a period 
of 6 months prior to the treatment procedure 
15. Negative pregnancy test results for female patients of childbearing potential (following the 
site’s usual practice) 
10.2.2 Randomization 
Patients who complete required baseline evaluations and meet eligibility criteria for the study 
may be enrolled. Randomization to treatment arm is accomplished by the investigator using 
an Interactive Web Response System. Patients recruited into the roll-in patient population 
will not be randomized. (Subjects participating in the Supplemental Clinical Study and 
Continued Access Study will not be randomized.) 
10.2.3 Blinding to assigned treatment 
All patients will be blinded to treatment assignment. Study personnel, who may be 
unblinded, should not disclose any treatment information to the patient prior to unblinding of 
study data. 
10.3 Ablation Procedure 
The following procedural requirements apply to all ablation procedures conducted during the 
study: 
1. An approved 3D mapping system will be used in all procedures consistent with device 
labeling in the case of the control device and with any compatible system in the case of the 
TactiCath Catheter. 
2. If TEE was not performed within the past 24 hours to assess atrial thrombus, an ICE 
assessment must be performed at the time of the procedure. In case of a positive finding, the 
procedure will be postponed and the patient placed on anticoagulation until freedom from 
thrombus can be confirmed. 
3. Enrollment, treatment, and peri-procedure follow-up of AF patients will conform to the 
HRS/EHRA/ECAS Expert Consensus Statement3 including a treatment strategy to isolate all 
PVs. 
4. A standard treatment scheme of mapping and ablation will be conducted during the 
interventional procedure followed by confirmation of entry block at 30 minutes after full 

 
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isolation of all PVs. In addition, IV isoproterenol (up to 20 μg/min) should be infused to test 
for both induced non-PV triggers and to elicit latent PV conduction. 
5. Any prior existing or induced supra-ventricular arrhythmia indicated for treatment with 
ablation should be treated as part of the PV isolation index procedure unless clinically 
contra-indicated. Pre-existing or induced typical AFL should be treated with ablation of the 
cavo-tricuspid isthmus line. If atypical flutter is induced, the decision to ablate is at the 
discretion of the physician.  
6. All ablations in the left atrium must be performed using the device specified by 
randomization. Use of a different device in the left atrium constitutes an acute treatment 
failure. 
7. In the absence of a clinical or induced arrhythmia, additional ablation lesion sets (e.g., 
prophylactic linear lesions, ablation of CFAE sites, etc.) should not be performed. 
8. PVI may be omitted if contraindicated in the judgment of the investigator in patients 
presenting with AVRT/AVNRT. 
9. In the TactiCath treatment group, contact force data will be provided to the operator and 
collected throughout the procedure. Intermittent catheter tip contact should be avoided during 
lesion creation. 
10. Ablation should be performed with the minimum power needed in the judgment of the 
investigator. The maximum RF power during ablation using the TactiCath study device is 
limited to 40W. Use of the control study device should follow the approved labeling and 
instructions for use. 
11. A multipolar “lasso” type mapping catheter will be deployed in the target vein pre- and post-
ablation to monitor PV potentials. 
12. Catheters will be irrigated at a continuous rate of 2 ml per minute (ml/min) when not 
ablating, and during ablation at a minimum of either 17 ml/min (RF power up to 30W) or 
30 ml/min. 
13. The integrity of the phrenic nerve should be evaluated before and after ablation of the right 
superior PV. In patients who are breathing spontaneously (not under general anesthesia), 
observe normal diaphragmatic excursion of the right hemi-diaphragm under fluoroscopy. In 
patients under general anesthesia, verify phrenic nerve functionality by placing a catheter in 
the lateral SVC and pacing the phrenic nerve. 
14. The lower level of anticoagulation should be maintained at an ACT of at least 300 
throughout the procedure, and higher targets (up to 400) may be used as indicated. 
15. Physicians are required to use each study device according to labeling and in a manner 
consistent with their standard clinical practice. In particular, the operator must not adapt or 
otherwise deviate from ablation technique normally employed when using the control device. 

 
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10.3.1 Peri-procedure Safety Recommendations 
Consistent with data published in the HRS/EHRA/ECAS Expert Consensus Statement on 
Catheter and Surgical Ablation for Atrial Fibrillation,3 the following peri-procedure 
precautions are strongly recommended to minimize risks to patient safety: 
 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. 
 Intracardiac echocardiography (ICE) – use of an ICE probe during the procedure to guide 
septal puncture and to monitor catheter position and manipulation is strongly recommended. 
 RF power settings in the TactiCath group – it is generally feasible to increase contact force 
rather than RF power, if needed, to produce an adequate lesion depth. RF power may be 
titrated downwards based on increased contact force according to the clinical judgment of the 
operator. In the TactiCath group, it is recommended that RF ablation be performed at an 
average contact force of approximately 20 grams.  
 Arrhythmia identification – it is recommended that a coronary sinus (CS) catheter be 
deployed past the Veussen's valve (into the great cardiac vein) to provide arrhythmia 
identification, linear lesion assessment, etc. Use of a diagnostic catheter in the right atrium 
(RA) is also recommended. 
10.4 Pre-discharge Procedure 
Post-interventional medication and treatment will be implemented according to the 
HRS/EHRA/ECAS Expert Consensus Statement.3 
The following post-treatment evaluations will be performed within 72 hours (or as indicated) 
after the treatment procedure and before discharging the patient: 
 TTE within 24 hours post-procedure is recommended to exclude pericardial effusion 
 General physical examination including vital signs 
 PT/PTT or INR following standard clinical practice 
 12-lead ECG 
 Recording of any cardiac medications, arrhythmia events, AEs, or protocol deviations 
10.5 Follow-up Procedures 
For the purpose of assessing study endpoints, patients will be followed for a total of 
12 months after the index procedure beginning with a 3-month blanking period and ending 
with a 9-month effectiveness assessment period. During the blanking period, up to 
2 additional RF ablation procedures may be performed (up to 10 days prior to end of the 
blanking period) and patients may be prescribed previously ineffective antiarrhythmic drugs. 
Patients indicated for a repeat procedure will be treated according to their initial 
randomization group. 

 
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Patients with treatment failure after the 3-month blanking period (i.e., symptomatic 
arrhythmia recurrence, re-treatment for AF with ablation, cardioversion for AF/AFL/AT, the 
use of Class I or Class III antiarrhythmic drugs.) and patients with more than 2 repeat 
ablations during the blanking period, will be followed per protocol but assessed for safety 
only. 
Subjects who experience a documented symptomatic episode of AF/AFL/AT (lasting longer 
than 30 seconds) during the 9-month effectiveness assessment period will be classified as a 
treatment failure. Documentation of the episode by standard 12 lead ECG recording may be 
shorter than 30 seconds in duration. 
Patients who do not experience treatment failure will undergo the following assessments 
described below at 7 days, at 3, 6, and 12 months post-index procedure, and every 6 months 
thereafter. Following the conclusion of the study, FDA may require a period of continued 
follow-up (Post-approval Study) that will last up to 5 years from the time of the initial 
procedure. Patients who withdraw before completing the study (Section 7.7) will be followed 
only through the date of their withdrawal. 
To avoid deviation from protocol, follow-up procedures must be completed during a window 
of time specified by the target date (time post-index procedure) and occurring within a fixed 
number of days/weeks before and after as described below. The schedule for follow-up 
procedures is determined by the date of the initial ablation procedure. Retreatment at any 
time will not ‘reset the clock’ for follow-up. 
10.5.1 7-Day Follow-up Procedure 
At 7 days post-index procedure (± 2 days) or at hospital discharge, whichever is later, 
patients will be contacted via telephone by the investigator for a safety assessment. The 
following data will be collected: 
 Cardiac medications 
 Arrhythmia events 
 Adverse events 
 Protocol deviations 
10.5.2 3-Month Follow-up Procedure 
At 3 months (± 2 weeks) post-index procedure, the following evaluations will be scheduled 
and data will be recorded: 
 Imaging study (CT scan or MRI, consistent with pre-treatment method, recommended but 
not required for Supplemental Clinical Study and Continued Access Study subjects) 
 Physical examination and vital signs 
 Cardiac medications 
 NYHA functional class 
 Arrhythmia events 
 Adverse events 

 
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 12-lead ECG 
 Protocol deviations 
 
10.5.3 6-Month Follow-up Procedure 
At 6 months (± 3 weeks) post-index procedure, the following evaluations will be scheduled 
and data will be recorded: 
 Physical examination and vital signs 
 Cardiac medications 
 NYHA functional class 
 Arrhythmia events 
 Adverse events 
 12-lead ECG 
 Protocol deviations 
10.5.4 12-Month Follow-up Procedure 
At 12 months (± 3 weeks) post-index procedure, the following evaluations will be scheduled 
and data will be recorded: 
 24-hour Holter monitoring (Section 10.8.2) 
 Physical examination and vital signs 
 Cardiac medications 
 NYHA functional class 
 Arrhythmia events 
 Adverse events 
 12-lead ECG 
 Quality of life questionnaire  
 Protocol deviations 
10.5.5 Extended Follow-up Procedure 
At every 6 months (± 4 weeks) following the effectiveness assessment period and until the 
device is approved, patients will be contacted via telephone by the investigator for a general 
health assessment. The following data will be collected: 
 Adverse events (related to survival and cardiac-related hospitalization) 
 Arrhythmia history 
10.5.6 Post-approval Study 
If deemed necessary by FDA, the requirements for a post-approval study will be specified by 
FDA at the time of device approval and will likely include periodic contacts with patients to 
assess general health and well-being. 

 
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10.6 Re-ablation Procedure 
10.6.1 Retreatment During the Blanking Period 
 
Patients may be re-treated with ablation up to two times during the blanking period but no 
later than 10 days before the end of the blanking period. Re-treatment during this interval 
will not constitute a treatment failure and must be performed with the device specified by the 
initial randomization.  
10.6.2 Retreatment After the Blanking Period 
 
Re-treatment after the blanking period will constitute a treatment failure. All re-ablation 
procedures after blanking must be performed with a commercially available device labeled 
for use in the US for the treatment of AF, e.g. the control device. 
10.7 Imaging for PV Stenosis 
If evidence of PV stenosis is seen at the 3-month follow-up when compared to the baseline 
scan, it is recommended that the subject undergo additional serial CT/MRI scans as deemed 
clinically appropriate by the investigator. 
10.8 Ambulatory Monitoring 
Ambulatory monitoring for symptomatic and asymptomatic episodes of AF will be 
conducted throughout the 9-month effectiveness assessment period. 
10.8.1 Transtelephonic Monitoring 
Patients will be issued a transtelephonic monitoring (TTM) device one month after the 
ablation procedure. They will be instructed to transmit an ECG weekly beginning with the 
3-month follow-up until 5 months after the index procedure, and then monthly until the end 
of the study. In addition to these recurring scheduled transmissions, patients will be 
instructed to record and transmit an ECG coincident with any occurrence of symptoms 
associated with AF at any time during follow-up. A core laboratory will review each 
recording and report findings to the investigator. 
10.8.2 Holter Monitoring 
Patients will be issued a Holter monitor at the 12-month follow-up and instructed to obtain a 
24-hour recording. A core laboratory will review each recording and report findings to the 
investigator. 

 
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10.9 Antiarrhythmic Drug Management 
10.9.1 Blanking Period 
It has been shown that AAD treatment during the 6 weeks after ablation for paroxysmal AF 
reduces the risk for early recurrence of atrial arrhythmias and the need for hospitalization or 
cardioversion.26 It is recommended that any current antiarrhythmic medication be continued 
following the ablation procedure. 
Current AADs may be withdrawn 4-6 weeks after ablation to assess for recurrence of 
symptoms and the necessity for re-ablation during the blanking period. 
If documented symptomatic AF recurs during the 3 month blanking period and the patient 
requires antiarrhythmic drug therapy, a previously ineffective but tolerated antiarrhythmic 
drug may be re-initiated to allow for the assessment of its effectiveness when combined with 
ablation.  
10.9.2 Effectiveness Assessment Period 
All Class I and Class III AADs will be discontinued at the end of the blanking period. The 
use of any Class I or Class III antiarrhythmic drug during the effectiveness assessment period 
will be considered an effectiveness failure.  Subjects enrolled in the Continued Access Study 
may be prescribed previously used Class I or Class III antiarrhythmic drugs. 
Beta-blockers, calcium channel blockers or digitalis may be used during the 9-month 
effectiveness assessment period if prescribed for reasons unrelated to arrhythmia 
management. Subjects are encouraged to continue their use through the end of the study 
unless it is determined to be unnecessary or detrimental by the investigator.  
Subjects who experience a recurrence of symptomatic PAF after the blanking period 
(treatment failure) should retry a previously failed AAD before a new medication is 
prescribed to evaluate the effectiveness of combined ablation and drug therapy. 
10.10 Anticoagulant Drug Management 
Anticoagulant drug regimen will follow the HRS/EHRA/ECAS Expert Consensus 
Statement.3 Warfarin is recommended for all patients following the AF ablation procedure. 
For patients with a CHADS (congestive heart failure, hypertension, age > 75 years, type 2 
diabetes, prior stroke or transient ischemic attack) score ≥ 2, continued use of warfarin is 
recommended. 
10.11 Early Termination Evaluation 
No formal early termination procedures will be conducted. Patients who withdraw before 
completing the study (Section 7.7) will be followed only through the date of their 
withdrawal. 

 
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11. PATIENT BENEFITS AND RISKS 
A risk analysis (per ISO 14971) of the medical device has been conducted through 
appropriate design control and confirmed by nonclinical bench, laboratory, and animal 
testing to minimize risks to the patient. 
11.1 Potential Benefits to Study Subjects 
Receiving benefit from participation in the study is not guaranteed. Anticipated benefits to 
patients may include, but are not limited to, the following: 
 Patients who receive treatment with the study device may experience shorter ablation 
procedure time and improved outcomes, although these objectives may not be demonstrated 
in this study  
 Patients who participate in the study may receive more frequent and/or detailed follow-up 
than is normally prescribed as standard of care in any given practice 
 Overall advancement of medical and scientific knowledge may benefit future patients with 
similar conditions  
11.2 Potential Risks to Study Subjects  
Risks to patients enrolled in this study include all those risks currently associated with all 
electrophysiology diagnostic procedures and RF catheter ablation procedures. The risks of 
the procedure are related primarily to mechanical injury to the heart and vessels from 
catheter manipulation and thermal injury due to RF current delivery, including the risk of 
thromboembolism and myocardial perforation, especially for ablations in the left atrium. 
 
For those procedures where the physician applies sedation or anesthesia, the standard risks of 
anesthesia also exist and include allergic reactions, pneumonia, aspiration pnuemonitis, 
atelectesis, prolonged sedation, other medical complications and in very rare cases, death.  
Complications associated with the use of the TactiCath Set may be related to the device or 
the procedure and they may include, but are not limited to the SAEs listed in Table 2 and the 
other AEs listed in Table 3. 
11.3 Clinical Events Committee 
An independent standing clinical events committee (CEC) consisting of members not 
otherwise associated with the trial, while blinded to treatment assignment, will review all 
SAEs and will adjudicate causality relative to the primary safety endpoints. The mode of 
operation of the CEC will be defined in a CEC Charter. Contact information for the CEC is 
provided in Appendix C. 
 

 
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11.4 Clinical Risk Analysis 
11.4.1 Increased Risks to Subjects Posed by the Investigation 
All patients who are enrolled in the study will undergo pre-procedure testing that is 
considered standard of care at the participating institution. The investigator is obliged per 
protocol to perform the ablation procedure in a manner consistent with device labeling and 
with their standard clinical practice. Subjects may be randomized to receive treatment with 
the TactiCath Set whose safety has not been assessed in a prospective, randomized trial.  
 
At most participating sites, patient follow-up procedures required per protocol are consistent 
with standard of care with the possible exception of an additional diagnostic scan at three 
months post-procedure and the use of diagnostic ambulatory monitoring throughout the 
follow-up period.  
 
The risks associated with the three month scan are the same as those for the baseline scan. 
For CT scans, the exposure to x-rays potentially increases the risk for cancer. For MR scans, 
the exposure to injected contrast agent may cause an allergic reaction. Risks associated with 
the use of an ambulatory monitor (TTM or Holter) may include abrasion of the skin from the 
recording electrodes. 
 
The addition of a diagnostic contact force sensor is not expected to introduce new procedural 
risks. Unexpected failure of this diagnostic feature should not interfere with other functional 
aspects of the device related to mapping, pacing and RF energy delivery. In the TOCCATA 
study, 23 patients treated with the TactiCath Set for AF experienced similar or less serious 
adverse events than the historical control (12% vs. 16.8%, n=34). 
 
In summary, the increased risks to which subjects will be exposed by the investigation are 
limited to the risk that they may be treated with an unproven device and that they may be 
exposed to additional follow-up testing as described above. 
11.4.2 Manner in Which Risks Will be Minimized 
A risk analysis of the TactiCath Set has been conducted according to ISO 14971 Application 
of Risk Management to Medical Devices. Precautions have been taken to minimize or 
eliminate risks through appropriate design controls as confirmed by nonclinical bench, 
laboratory and animal testing. In addition, a multi-center, non-randomized prospective 
clinical safety and performance study was conducted in Europe, the TOCCATA study.23 In 
this study, 76 patients (34 AF, 27 AFL, and 15 other supraventricular tachycardias) were 
treated with a TactiCath catheter (version number PN-001 065) and followed for one year. 
The safety endpoints of this study were met and used to support a successful application for 
CE mark in May 2009. 

 
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Patients treated with the study device will undergo an established procedure for which 
published guidelines exist1-4 and whose outcomes are documented in the literature.7-8, 27 The 
procedural and follow-up requirements and recommendations within this clinical 
investigational plan reference these guidelines with the intention that patients will be 
managed consistently. 
Risks associated with the three month scans will be minimized by excluding patients from 
the study with a known contraindication to computed tomography or magnetic resonance 
angiography. 
Risks associated with the ablation procedure will be minimized by requiring operators to 
assess for atrial thrombus prior to ablation, to employ an approved 3D mapping system, to 
maintain adequate irrigation and appropriate anti-coagulation, and to monitor for potential 
injury to the esophagus and phrenic nerve as part of the procedure.  
In addition, participating sites have been chosen for their demonstrated proficiency with both 
3D mapping systems that will be used (Carto and NavX) and will be trained extensively on 
the requirements of the protocol. Field clinical engineers trained in the use of the study 
device and the requirements of the protocol may monitor ablation procedures in the study. 
Sites will be monitored soon after enrollment begins to identify and address protocol 
deviations and unsafe practices, if any exist, in a timely manner.  
Frequent personal contact with subjects throughout the follow-up period by the investigator 
and by TTM monitors trained to elicit patient complaints will help identify patients in need 
of medical care. 
11.4.3 Justification for the Investigation 
The availability of contact force data during catheter manipulation is intended to guide the 
safe and effective creation of ablation lesions by providing essential feedback to the operator 
related to catheter placement. 
The TactiCath catheter closely resembles a standard irrigated RF ablation catheter with 
respect to design, materials and usage. The incorporation of a diagnostic contact force sensor 
in the distal tip is an incremental feature with potential implications for improved safety and 
effectiveness. If desired, the force sensor data may be disregarded and the device may be 
employed similarly to a standard, commercially available RF ablation catheter. 
The high rate of arrhythmia recurrence in this population has been shown to be the result of 
restored conduction between previously isolated pulmonary veins and the left atrium. 
Patients with recurrence frequently undergo one or more repeat ablation procedures, 
subjecting them to repeated procedural risks. 
Electrical reconnection is believed to result from inadequate lesion formation during 
ablation. Contact force measured between the ablation catheter tip and the tissue being 
ablated may be used to position the catheter to produce a sufficiently transmural lesion and 
theoretically promote better long-term isolation of the PVs. 

 
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The TOCCATA study demonstrated safety in a small population (n=76) and showed a 
correlation between higher contact force and freedom from recurrence. Based on these 
considerations, the clinical investigation of the TactiCath Set is justified. 
11.4.4 Description of Patient Population 
A pre-defined sample of patients prescribed for PAF will be enrolled such that a statistically 
valid result may be obtained. In general, the distribution of age and gender is expected to 
reflect the incidence of PAF in the US and Europe with mean age in the mid to upper 50s and 
approximately one third female subjects. 
 
Per protocol, all subjects will have failed one or more anti-arrhythmic medications and will 
have symptoms during AF. Thus, the patient population being studied will be indicated for 
further treatment with ablation according to published guidelines. 
11.4.5 Adverse Events 
 
The definitions for adverse events, adverse device effects and unanticipated adverse device 
effects are provided in section 12.1 of the protocol. A tabulation of adverse events and the 
criteria that will be used to assess severity is provided in section 12.2 of the protocol. 
Potential adverse events that may be associated with the ablation procedure are provided in 
section 12.3 of the protocol. Sponsor and investigator obligations for reporting adverse 
events are described in section 12.4 of the protocol.  
11.5 Conclusion 
An extensive Risk Analysis and Risk Mitigation plan has been implemented to minimize any 
residual risk of the TactiCath Set to the patient. 
Hands-on training opportunities will be provided for operators who are unfamiliar with the 
study device. These may include simulations, using the study device in the nonclinical 
setting, or the observation of clinical use of the study device by experienced operators. 
We believe that the availability of catheter contact force information during a procedure may 
convey a benefit to the patient and outweigh any potential residual risk. 
12. ADVERSE EVENTS 
12.1 Definitions 
12.1.1 Adverse Events 
An AE is defined as any untoward medical occurrence in a patient. This definition does not 
imply that there is a relationship between the adverse event and the device under 
investigation. 

 
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An AE will not be reported if it existed at enrollment and continued unchanged thereafter 
unless the event worsened considerably and required additional medical or pharmacological 
treatment. Investigators in this study are required to report all AEs except for the following: 
 Standard follow-up or exacerbation of pre-existing conditions unrelated to the 
cardiovascular system including diabetes, cancer/tumors, multiple sclerosis, allergies, 
osteoporosis, arthritis, emphysema, vision or aural problems and rectal polyps. 
 Physical trauma determined to be unrelated to the ablation procedure including pain 
due to musculoskeletal injuries, muscle aches due to over-exertion, joint degeneration, 
tendonitis and bursitis and burns from external causes. 
 Newly developed disease or illness unrelated to AF, the ablation procedure, a study 
device or the drugs used to treat cardiovascular illness including gastrointestinal ulcers, 
hemorrhoids, immune system deficiencies like HIV or AIDS, infectious diseases like 
hepatitis or herpes viruses, neurological/psychological disorders such as Alzheimer’s, 
Parkinson’s, dementia, obsessive/compulsive or eating disorders. Other illness, if clearly 
isolated from the cardiovascular disease, including jaundice unrelated to systemic infection, 
infection in extremities unrelated to the procedure, bacterial infection or cellulitis. 
 Common ailments unrelated to the cardiovascular system, the ablation procedure, a 
study device or the drugs used to treat cardiovascular illness including common 
headache, muscle pain, food poisoning, superficial infections, rashes, warts, shingles, 
constipation, eczema, hernias, upper respiratory infections or influenza. 
12.1.2 Adverse Device Effects 
An ADE is defined as any untoward and unintended response to a medical device. This 
definition includes any event resulting from insufficiencies or inadequacies in instructions 
for use or deployment of the device. This definition also includes any event that is a result of 
user error. 
12.1.3 Serious Adverse Events 
All SAEs will be reported. An SAE is defined as any event that 
1. Leads to death, 
2. Leads to serious deterioration in the health of a patient that: 
a. Results in a life-threatening illness or injury, 
b. Results in a permanent impairment of a body structure or a body function, 
c. Requires in-patient hospitalization or prolongation of existing hospitalization, 
d. Results in medical or surgical intervention to prevent permanent impairment to a body 
structure or a body function. 
3. Leads to fetal distress, fetal death, or a congenital abnormality or birth defect. 

 
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12.1.4 Serious Adverse Device Effects 
A serious adverse device effect (SADE) is defined as an ADE that results in any of the 
consequences characteristic of an SAE or that may lead to any of these consequences if 
suitable action is not taken or intervention is not made or if circumstances are less opportune. 
12.1.5 Unanticipated Adverse Device Effects (United States sites only) 
An unanticipated ADE is defined as any SADE on health or safety or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, problem, or death has 
not been previously identified in nature, severity, or degree of incidence in the CIP or 
application (including a supplementary plan or application), or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or welfare of 
patients. 
12.2 Primary Serious Adverse Events 
Primary serious adverse events (PSAEs) related to the use of a study device (TactiCath or 
control) are defined as having occurred within 7 days of the ablation procedure or prior to 
pre-discharge, whichever is later, and diagnosed at any time during the follow-up period.  
PSAEs that meet the severity criteria described in Table 2 will contribute to the primary 
safety endpoint only in patients in whom a study device has been introduced. 
Hospitalizations solely for arrhythmia recurrence (without coexisting conditions such as 
thromboembolism, worsening heart failure, etc.) will not be considered primary SAEs. 
PSAEs include but are not limited to: 
 
Table 2 Primary Serious Adverse Events  
Primary Serious Adverse Event 
Severity Criteria 
Atrial perforation 
Visible (either with radiographic and/or 
ultrasonagraphic imaging and/or direct 
visualization) movement of ablation catheter, 
needle or sheath through the atrial wall as 
evidenced by bleeding and the need for 
pericardial drainage or surgical intervention 
Death 
Adverse event resulting in patient death 
Diaphragmatic paralysis 
Change in baseline diaphragmatic function as 
evidenced by elevation of a hemi-diaphragm 
above its normal position or loss of normal 
respiratory excursion but not due to a 
pulmonary process such as atelectasis and 
persisting longer than the end of the procedure 
AV block 
New, persistent 2nd or 3rd degree AV block not 
attributable to a vasovagal reaction or 

 
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medication effect and requiring permanent 
pacing 
Gastroparesis 
Gastroparesis as a result of ablation requiring 
intervention or hospitalization 
Hospitalization (initial or prolonged) 
Adverse event leading to new hospital 
admission or extension of initial hospital stay 
beyond expected timeframe due to ablation 
procedure-related cause. Excludes 
hospitalization solely for arrhythmia recurrence. 
Left-atrial-esophageal fistula 
Creation of a direct communication (fistula) 
between the left atrium and esophagus 
necessitating surgical intervention or resulting 
in permanent impairment (e.g. due to 
hemorrhage or septic emboli) 
Myocardial Infarction 
Requires 2 of the following 3 criteria: 
• Elevation of biochemical markers of 
myocardial necrosis (preferably troponin) 
• Ischemic Symptoms 
• Development of pathologic Q waves on the 
ECG or persistent ECG changes indicative of 
ischemia (ST segment elevation or depression) 
Pericarditis 
 
Pleuritic chest discomfort associated with either 
pericardial rub and/or ECG changes that 
requires or prolongs hospitalization 
Pneumothorax 
Identification of air in the pleural space which 
either prolongs hospital stay (for observation) or 
requires surgical intervention or chest tube 
placement 
Pulmonary edema 
Pulmonary alveolar fluid accumulation 
accompanied by typical symptoms (dyspnea), 
physical findings (rales, hypoxemia), radiologic 
findings, and response to diuretic therapy and 
requiring hospitalization 
Stroke 
Brain disorder involving loss of brain functions 
(that persists for > 24 hours) that occur when 
the blood supply to any part of the brain is 
interrupted as determined by the consulting 
neurologist 
PV stenosis 
Severe (≥ 70%), or complete occlusion of a PV, 
even in the absence of symptoms 

 
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Tamponade 
Pericardial effusion of sufficient size to cause 
hemodynamic compromise and requiring 
drainage based on hypotension, 
echocardiographic findings or other clinical 
factors 
Thromboembolism 
Deep vein thrombosis or pulmonary embolism 
Transient ischemic attack 
Acute episode of temporary (< 24 hrs.) and 
focal loss of cerebral function of vascular 
(occlusive) origin as determined by the 
consulting neurologist 
Vascular access complications 
Vascular access complication requiring surgical 
repair, blood transfusion (e.g., groin hematoma, 
AV fistula) or significant intervention such as 
thrombin injection (e.g., pseudoaneurysm) 
 
12.3 Procedure and Device Related Adverse Events 
Adverse events that occur in conjunction with the ablation procedure (most also listed in the 
TactiCath Set Instructions for Use) are listed below in Table 3. These AEs will contribute to 
the secondary safety endpoint in all enrolled patients. AEs will be classified as primarily 
related to the procedure or to the device. Device related SAEs and SAEs whose origin is 
unclear will be reported to the CEC for adjudication as potential PSAEs. 
 
Table 3 Adverse Events Associated with Radiofrequency Ablation 
Procedure Related 
Possibly Device Related 
Air embolism 
X 
Cardiac perforation 
X 
Cardiac thromboembolism 
X 
Cerebrovascular attack 
X 
Chest pain/discomfort 
X 
Complete AV block 
X 
Coronary artery dissection 
 
Coronary artery spasm 
X 
Coronary artery thrombosis 
X 
Gastroparesis 
X 
Hemothorax 
 
Myocardial Infarction 
X 
Pericardial effusion 
X 
Pericarditis 
X 
Phrenic nerve injury 
X 

 
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Pneumothorax 
 
Pseudoaneurysm 
 
Pulmonary edema 
X 
Pulmonary embolism 
 
Pulmonary vein stenosis 
X 
Tamponade 
X 
Thrombosis 
 
Transient ischemic attack 
X 
Valvular damage 
X 
Vascular access complications 
 
Venous Thromboembolism and vasovagal reactions 
 
Ventricular tachyarrhythmia 
X 
12.4 Handling and Reporting of Adverse Events 
Patients will be carefully monitored during the study for possible AEs. Any AE will be 
followed to a satisfactory resolution, until it becomes stable, or until it can be explained by 
another known cause(s) (i.e., concurrent condition or medication) and clinical judgment 
indicates that further evaluation is not warranted. All findings relevant to the final outcome 
of an AE must be reported in the patient’s medical record. 
The clinical investigator will attempt to assess the involvement of the investigational device 
in the AE. All observations and clinical findings, including the nature, severity, and 
relationship, will be documented on the appropriate eCRFs. 
In case of death, the clinical investigator must make every effort to obtain a copy of the 
autopsy report and/or death certificate and transmit this to Premier Research Group Limited 
(Premier Research). The patient’s private information shall be concealed prior to transmittal 
to Premier Research. 
The clinical investigator will report all SAEs and ADEs to Premier Research by telephone or 
fax within 7 days at the number provided by Premier Research. The clinical investigator will 
provide a detailed written report within 14 days.  
Premier Research will discuss with the clinical investigator and the safety advisory 
committee (as applicable), all ADEs and SAEs and coordinate appropriate actions, in 
particular their notification to other clinical investigators and to the appropriate regulatory 
agencies as applicable. 
For any event where there is a suspicion that the device is involved, Endosense may request 
that the clinical investigator return the device (when possible) for investigation at 
Endosense’s laboratory. Endosense will provide a procedure for cleaning and preparation as 
well as special kits for the return of used and potentially bio-hazardous materials.  
 

 
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12.4.1 European Reporting Obligations for European Investigators 
All SAEs must be reported to the IEC as per local regulations. 
All SADEs must be reported by both the clinical investigator and Premier Research to the 
CA as per national regulations and in accordance with the applicable sections of Medical 
Devices Directive 93/42/EEC and ISO 14155. 
12.4.2 United States Reporting Obligations for United States Investigators 
All SAEs must be reported to the IRB who approved the study within 7 days (or sooner if so 
specified by local IRB policy). 
All SADEs and UADEs must be reported by Premier Research to the Food and Drug 
Administration (FDA) within 10 days after Premier Research is first made aware of the 
event. Reporting to the FDA will be consistent with 21 CFR Part 812.150. 
12.5 Early Termination or Suspension of the Clinical Investigation 
An independent data safety monitoring board (DSMB) comprised of members not otherwise 
associated with the trial will convene periodically to assess overall study safety. The DSMB 
will make recommendations regarding suspension of the study on the basis of predefined 
conditions related to the incidence of AEs. The mode of operation of the DSMB will be 
defined in a DSMB Charter. Contact information for the DSMB is provided in Appendix D. 
The DSMB can use the decision rules described in Appendix A as a reference. However, the 
DSMB can make its own recommendations based on aggregated information. The DSMB 
and Endosense will decide if the suspension of the study will be followed by a termination. 
13. DATA QUALITY ASSURANCE 
The study described in this CIP will be implemented according to the local regulatory 
requirements (FDA, EU) and GCP. All procedures not described in this protocol will be 
performed according to approved written Standard Operating Procedures (SOPs) unless 
otherwise stated. 
Steps to assure the accuracy and reliability of data include the selection of qualified clinical 
investigators and appropriate study sites, review of CIP procedures with the clinical 
investigator and associated personnel prior to the study, and periodic monitoring visits by 
Premier Research. Premier Research will review data for accuracy and completeness during 
and after on-site monitoring visits, and any discrepancies will be resolved with the clinical 
investigator or designees as appropriate. 
13.1 Case Report Forms 
The electronic case report forms (eCRFs) contain confidential material. Specific training on 
the completion of eCRFs will be provided to the clinical investigator and other site personnel 

 
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as appropriate. The clinical investigator is responsible for the accuracy and completeness of 
data reported on eCRFs.  
The clinical research associate (CRA) will periodically verify the data entered onto the 
eCRFs against source documents to ensure data integrity, accuracy, and completeness of the 
data prior to locking the eCRFs for tabulation of study endpoint data. 
13.2 Monitoring Procedures 
Premier Research monitors will conduct site visits to the study facilities to monitor the study 
and ensure compliance with the CIP, GCP, and applicable regulations and guidelines.  
The clinical investigator agrees to allow these monitors and other authorized Endosense 
representatives access to the clinical supplies dispensing and storage area and to study 
documentation for the above mentioned purpose and agrees to assist the monitors in their 
activities, if requested. Requests by regulatory agencies to inspect the study sites may be 
made. The clinical investigator agrees to allow inspectors from regulatory agencies to review 
records and to assist the inspectors in their duties, if requested. 
Source documents include the physician or hospital patient records that are maintained at the 
study site. In most cases, the source documents will be the physician or hospital patient chart. 
In some cases, the source documents may be electronic. In both cases, the information 
captured on the eCRF must match the information in the chart or electronic source document. 
Periodically, the Premier Research monitor or Endosense representative will visit the study 
site for the purpose of directly comparing the data in the eCRF with the source. The clinical 
investigator agrees to make source documents (hard copy or electronic) available for this 
purpose. 
It is the clinical investigator’s responsibility to ensure accurate completion of the eCRFs and 
to approve the eCRFs. The clinical investigator or a designated sub investigator recognized 
by the IEC or IRB has the authority to sign eCRFs. These electronic signatures serve to attest 
that the information contained in the eCRF is accurate and true. 
13.3 Data Management 
The standard procedures for handling and processing records will be followed per GCP and 
Premier Research’s SOPs.  
A comprehensive Data Management Plan will be developed including a Data Management 
Overview, Database Contents, annotated eCRF, Pre-Entry Review List, Self-evident 
Correction Conventions, Query Contacts, and Consistency Checks. 

 
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14. INVESTIGATIONAL PRODUCT TRACEABILITY AND RECORDING 
Device accountability will be maintained during the study. Each site will document all used 
and unused devices received, stored, dispensed, and returned to Endosense as applicable. 
Inventory records will be periodically monitored by the CRA. 
14.1 Device Complaints and Malfunctions 
Device complaints may reflect any deficiencies related to the study device, instructions for 
use, operator’s manual, or other product-related documentation.  
Device complaints may or may not involve a clinical event. If the device complaint is based 
on a clinical event, the event must be recorded as an adverse device effect (ADE) as outlined 
in Section 12.1.2 of this clinical investigational plan (CIP). 
14.2 Complaint Reporting 
If any study device complaints occur (e.g., instructions for use, operator’s manual, or other 
product-related documentation), the clinical investigator will document the complaint(s) 
using the appropriate form(s).  
15. ETHICS 
15.1 Declaration of Helsinki 
The study will be conducted according to the guidelines established in the Declaration of 
Helsinki. Patients will be free to withdraw from the study at any time without prejudice to 
their subsequent treatment. 
15.2 Institutional Review Board or Independent Ethics Committee Approval 
This study will be conducted in compliance with the Declaration of Helsinki and its 
amendments and the applicable regulations of the country in which the study is conducted. 
A properly constituted, valid Institutional Review Board (IRB) or Independent Ethics 
Committee (IEC) must review and approve the CIP, the investigator’s informed consent 
document, and related patient information and recruitment materials before the start of the 
study. 
15.3 Informed Consent 
Informed consent shall be obtained in writing and documented before a patient is enrolled in 
the clinical investigation in accordance with the principles of Informed Consent, according to 
the Declaration of Helsinki, Good Clinical Practice (GCP), 21 Code of Federal Regulations 
(CFR) Part 50, the Medical Devices Directive 93/42/EEC, and International Organization for 
Standardization (ISO) 14155-1, Chapter 6.7.1. 

 
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It is the responsibility of the clinical investigator to ensure that written informed consent is 
obtained from the patient (or legally acceptable representative) before any activity or 
procedure is undertaken that is not part of routine care. 
15.4 Patient Identification and Confidentiality 
Patient identification and confidentiality will be ensured according to the terms and 
definitions in ISO 14155-1, Chapter 6.5. This includes but is not limited to the following: 
1. Patients will be identified on all eCRFs by a unique reference code including the patients’ 
initials. 
2. ECRFs are confidential documents and will only be available to Endosense (including 
delegates, such as CRAs) the clinical investigator, the biostatistician, and if requested, to the 
advisory committee and regulatory authorities. Selected ECRFs will also be available to the 
independent clinical lab responsible for collecting and entering the results of ambulatory 
monitoring tests (Appendix F). The principal clinical investigator for each center will 
maintain, as part of the investigation file, a list identifying all patients entered into the trial. 
16. REGULATORY REQUIREMENTS 
16.1 Compliance With Regulations Applicable to Clinical Trials 
The study will be conducted according to the laws, regulations and administrative provisions 
relating to the implementation of GCP in the conduct of clinical trials, as applicable by 
national legislation and European Union (EU) Directives, including 93/42/EEC, ISO 
14155-1, ISO 14155-2, 21 CFR Part 812, and local regulations where applicable. 
16.2 Competent Authority Notification 
When required, Endosense will provide notice to the Competent Authority (CA) that the 
clinical trial is scheduled to begin and obtain regulatory clearance whenever required by 
national law. 
Any applicable notifications or submissions must also be made to the relevant CA regarding 
data protection. 
17. CHANGES TO THE CIP OR RELATED PROCEDURES 
This CIP cannot be altered or changed except through a formal CIP amendment, which 
requires the written approval of Endosense. 
The CIP amendment(s) must be signed by the clinical investigator and approved by the IRB 
or IEC before implementation. The CIP amendments will be filed with the appropriate 
regulatory agency(s) having jurisdiction over the conduct of the study. 

 
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Note: Substantial changes may require approval from the FDA, IRB, IEC, and the CA prior 
to implementation. 
18. DEVIATIONS FROM THE CIP 
Any deviation from the CIP must be recorded along with an explanation for the deviation. 
The clinical investigator will report each deviation to Endosense. Significant deviations will 
be reported to the IEC or IRB within the appropriate deadlines stipulated by the appropriate 
regulatory agency(s) and according to local SOPs. 
Significant deviations are defined as those impacting or potentially impacting patient safety, 
enrollment of non-eligible patients, and any deviation that significantly compromises the 
outcome of the study. 
Note: Where relevant, the Competent Authorities should be informed. 
19. GENERAL CONSIDERATIONS 
19.1 Discontinuation of the Study 
Endosense reserves the right to discontinue this study for safety or administrative reasons at 
any time. In such events, patients will be followed to assess safety through the entire planned 
follow-up period. 
19.2 Use of Information and Publication 
All information concerning the TactiCath Set, Endosense operations, patent applications, 
manufacturing processes, and basic scientific data supplied by Endosense or Premier 
Research to the clinical investigator and not previously published, is considered confidential 
and remains the sole property of Endosense. The eCRFs also remain the property of 
Endosense. The clinical investigator agrees to use this information for purposes of study 
execution through finalization. 
The information developed in this study will be used by Endosense in connection with the 
continued development of the TactiCath Set and thus may be disclosed as required to other 
clinical investigators or government regulatory agencies. 
Publication or other public presentation of the TactiCath Set data resulting from this study 
requires prior review and written approval of Endosense according to the TOCCASTAR 
Publication Policy. Abstracts, manuscripts, and presentation materials should be provided to 
Endosense for review at least 30 days prior to the relevant submission deadline. 
20. REFERENCES 
1. Blomström-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/AHA/ESC Guidelines for 
the management of patients with supraventricular arrhythmias--executive summary. A report 

 
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of the American college of cardiology/American heart association task force on practice 
guidelines and the European society of cardiology committee for practice guidelines (writing 
committee to develop guidelines for the management of patients with supraventricular 
arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society. J Am Coll 
Cardiol. 2003; 42(8): 1493-1531. 
2. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines 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 European Society of Cardiology Committee for Practice Guidelines (Writing Committee 
to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am 
Coll Cardiol. 2006; 48(4): 854-906. 
3. Calkins H, Brugada J, Packer DL, et al. HRS/EHRA/ECAS expert consensus statement on 
catheter and surgical ablation of atrial fibrillation: recommendations for personal, policy, 
procedures and follow-up. 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) and the European Cardiac Arrhythmia Society 
(ECAS); in collaboration with the American College of Cardiology (ACC), American Heart 
Association (AHA), and the Society of Thoracic Surgeons (STS). Endorsed and approved by 
the governing bodies of the American College of Cardiology, the American Heart 
Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm 
Association, the Society of Thoracic Surgeons, and the Heart Rhythm Society. Europace. 
2007; 9(6): 335–379. 
4. Natale A, Raviele A, Arentz T, et al. Venice Chart international consensus document on 
atrial fibrillation ablation. J Cardiovasc Electrophysiol. 2007; 18(5): 560-580. 
5. PMA P030031: Biosense Webster NaviStar®/Celsius® ThermoCool® Diagnostic/ Ablation 
Deflectable Tip Catheters - P030031. Issued 06 Feb 2009. 
6. Wilber DJ, Pappone C, Neuzil P, et al. Comparison of antiarrhythmic drug therapy and 
radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized 
controlled trial. JAMA. 2010; 303(4): 333-340. 
7. Cappato R, Calkins H, Chen SA, et al. Worldwide survey on the methods, efficacy and safety 
of catheter ablation for human atrial fibrillation. Circulation. 2005; 111(9): 1100-1105. 
(Updated 2010; 3; 32-38.) 
8. Cappato R, Calkins H, Chen SA, et al. Prevalence and causes of fatal outcome in catheter 
ablation of atrial fibrillation. J Am Coll Cardiol. 2009; 53(19): 1798-1803. 
9. Yokoyama K, Nakagawa H, Shah DC, et al. Novel contact force sensor incorporated in 
irrigated radiofrequency ablation catheter predicts lesion size and incidence of steam pop and 
thrombus. Circ Arrhythm Electrophysiol. 2008; 1(5): 354-62. 

 
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10. Shah DC, Lambert H, Saoudi N, et al. Catheter tip force required to mechanically perforate 
the cardiac free wall. Poster presented at: Heart Rhythm 2008 29th Annual Scientific 
Sessions; 14-17 May 2008; San Francisco, CA. Abstract 6127, PO1-68. 
11. Shah DC, Lambert H, Nakagawa H, et al. Correlation of real-time measurement of ablation 
catheter tip force with subjective tissue contact assessment in the beating heart. Poster 
presented at: Heart Rhythm 2008 29th Annual Scientific Sessions; 14-17 May 2008; San 
Francisco, CA. Abstract 6099, PO1-67. 
12. Ikeda A, Nakagawa H, Shah DC, et al. Role of contact force in esophageal injury during left 
atrial radiofrequency ablation. Poster presented at: Heart Rhythm 2008 29th Annual 
Scientific Sessions; 14-17 May 2008; San Francisco, CA. Abstract 6317, PO5-26. 
13. Ikeda A, Nakagawa H, Shah DC, et al. Radiofrequency ablation catheter with contact force 
sensor predicts lesion size and incidence of steam pop in the beating canine heart. Poster 
presented at: Heart Rhythm 2008 29th Annual Scientific Sessions; 14-17 May 2008; San 
Francisco, CA. Abstract 4543, PO1-57. 
14. Ikeda A, Nakagawa H, Shah DC, et al. Electrogram parameters (injury current, amplitude 
and dV/dt) and impedance are poor predictors of electrode-tissue contact force for 
radiofrequency ablation. Poster presented at: Heart Rhythm 2008 29th Annual Scientific 
Sessions; 14-17 May 2008; San Francisco, CA. Abstract 4570, PO5-41. 
15. Di Biase L, Arruda M, Armaganijan L, et al. Real time monitoring of tip electrode-tissue 
orientation and contact force: optimizing accuracy and safety of mapping and ablation 
procedures. Paper presented at: ACC.08 57th Annual Scientific Session; 29 Mar-
01 Apr 2008; Chicago, IL. Abstract 811-3. 
16. Thiagalingam A, d’Avila A, Foley, L, et al. Abstract 2239: The relationship between 
impedance change and catheter contact force during radiofrequency ablation: evaluation in a 
porcine ex vivo cardiac model using a novel force-sensing irrigated tip ablation catheter. 
Circulation. 2007; 116:II_487. 
17. Yokoyama K, Nakagawa H, Shah DC, et al. Novel radiofrequency ablation catheter with 
contact force sensor predicts lesion size and incidence of steam pop in canine model. Poster 
presented at: Heart Rhythm 2007 28th Annual Scientific Sessions; 9-12 May 2007; Denver, 
CO. Abstract PO5-106. 
18. Shah DC, Leo G, Aeiby N, et al. Evaluation of a new catheter sensor for real-time 
measurement of tissue contact. Paper presented at: Heart Rhythm 2006 27th Annual 
Scientific Sessions; 17-20 May 2006; Boston, MA. Abstract AB36-6. 
19. Shah DC, Lambert H, Nakagawa H, et al. Force-time integral predicts lesion size in 
contractile model simulating beating heart. Poster presented at: Heart Rhythm 2009 30th 
Annual Scientific Sessions; 13-16 May 2009; Boston, MA. Abstract PO01-46. 

 
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20. Ikeda A, Nakagawa H, Lambert H, et al. Prediction of equivalent lesion size and incidence of 
steam pop by controlling contact force and radiofrequency power in canine beating heart. 
Poster presented at: Heart Rhythm 2010 31st Annual Scientific Sessions; 12-15 May 2010; 
Denver, CO. Abstract 4726, Poster PO1-74. 
21. 15th Annual Boston Atrial Fibrillation Symposium; 14-16 Jan 2010. MiniSymposium on 
contact force sensing. Moderator: Keane D. http://www.afsymposium.com/program.aspx. 
Accessed 12 Mar 2010. 
22. Piorkowski C, Sih H, Sommer P, et al. First in human validation of impedance-based catheter 
tip-to-tissue contact assessment in the left atrium. J Cardiovasc Electrophysiol. 2009; 20(12): 
1366-1373. 
23. TOCCATA Clinical Investigation Report VR-001 148 Version C – 12 months follow-up, 
Endosense TOCCATA 12-month report 
24. TactiSys™ User Manual. PR-002 107 A (US). Endosense 
25. Cui L, Hung HMJ, Wang SJ. Modification of sample-size in group sequential trials. 
Biometrics. 1999; 55(3): 853-857. 
26. Roux JF, Zado E, Callans DJ, Garcia F, Lin D, Marchlinski FE, et al. Antiarrhythmics After 
Ablation of Atrial Fibrillation (5A Study). Circulation 2009;120;1036-1040 
27. Ip S, Terasawa T, Balk EM, Chung M, Alsheikh-Ali AA, Garlitski AC, Lau J. Comparative 
Effectiveness of Radiofrequency Catheter Ablation for Atrial Fibrillation. Comparative 
Effectiveness Review No. 15. (Prepared by Tufts Medical Center Evidence-based Practice 
Center under Contract No. 290-02-0022.) Rockville, MD: Agency for Healthcare Research 
and Quality. July 2009. 
28. John Spertus, MD, MPH, Paul Dorian, MD, Rosemary Bubien, RN, MSN, Steve Lewis, 
PhD, Donna Godejohn, BS and Caroline Burk, PharmD. Validation of the Atrial 
Fibrillation Effect on QualiTy-of-life (AFEQT) Questionnaire for Atrial Fibrillation 
(AF): A New Disease-Specific Health Status Measure. Poster presented at: Heart Rhythm 
2010 31st Annual Scientific Sessions, 13 May, 2010; Denver, CO. Abstract PO3-54. 
29. Neuzil P, Shah D, Herrera C, Jais P. Hindrick G, Natale A, Fonck E, Lambert H, Kuck 
KH, Reddy V. Does Catheter Contact Force During RF Ablation Relate to AF 
Recurrence Rate? Poster presented at: Cardiostim 2010 – 17th World Congress; 16-19 
June 2010; Nice, France. Abstract 176P/7. 
30. Calkins H, Kuck H, 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 

 
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Heart Rhythm Association (EHRA) and the European Cardiac Arrhythmia Society (ECAS); 
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, 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: 632-696. 

 
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21. APPENDICES 
APPENDIX A ............................................................................................. Statistical Methods 
A.1 
Determination of Sample Size 
A.1.1 
Assumptions 
Data from the NaviStar® ThermoCool® Catheter premarket approval (PMA) study showed 
that the treatment success rate at the end of the 9-month post-blanking follow-up period was 
47% in the ThermoCool arm versus 18% in the antiarrhythmic drug arm after excluding a 
single site that was considered substantially different from the other sites. Data from the 
Endosense TOCCATA study using the TactiCath catheter also suggested a treatment success 
rate of approximately 48%. After excluding treatment failures due to the use of beta-
blockers, calcium channel blockers, or angiotensin-converting enzyme inhibitors that will not 
contribute to the endpoint of the TOCCASTAR study, treatment success rate is expected to 
be around 55%. 
Data from the NaviStar® ThermoCool® Catheter PMA study showed that the incidence of 
primary device or procedure related SAEs with an onset within 7 days of the procedure was 
13% after excluding a single site that was considered substantially different from the other 
sites. This rate was 12% in the TOCCATA study. Hospitalization solely due to AF/AFL/AT 
recurrences (approximately 3% based on the NaviStar® ThermoCool® Catheter PMA study 
and the TOCCATA study) will not be considered as device or procedure related SAEs in this 
study. Therefore, the incidence of primary SAEs within 7 days of the index procedure is 
expected to be ≥ 9% in the TOCCASTAR study. 
A.1.2 
Non-inferiority Margins 
This study aims to demonstrate non-inferiority of the TactiCath Set to the control device in 
both effectiveness and safety. Non-inferiority margin is 15% for effectiveness (treatment 
success rate at the end of the 9 month effectiveness assessment follow-up period 
post-blanking) and 9% for safety (incidence of primary SAEs with onset within 7 days of the 
index procedure or prior to hospital discharge and diagnosed throughout the study). 
A.1.3 
Sample Size 
Let Pt denote the percent of treatment success or the incidence of primary SAEs in the 
TactiCath treatment group and Pc denote the corresponding rate in the control treatment 
group. Under these assumptions, a total of 274 patients (137 patients per treatment group) 
will provide 80% power to reject the null hypothesis that (Pt - Pc ≤ -0.15) with a one-sided 
0.05 significance level for the primary effectiveness endpoint. A total of 274 patients 
(137 patients per treatment group) will provide 83% power to reject the null hypothesis that 
(Pt - Pc ≥ 0.09) with a one-sided 0.05 significance level for the primary safety endpoint. We 
further assume that approximately 10% of the randomized patients can be excluded from the 

 
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denominator due to early terminations clearly unrelated to study device, or excluded from the 
per-protocol population due to major protocol violations. Therefore, the study will randomize 
approximately 300 patients. 
In addition, to allow for a period of familiarization with the unique features of the TactiCath 
Set, each site will be permitted to enroll up to 5 roll-in patients who will not be randomized. 
The number of roll-in patients in the entire study shall be limited to 100.   
In order to prevent bias in the results due to different performance of a single site, no more 
than 15% of patients will be enrolled at any one site. 

 
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A.2 
Interim Analyses 
One planned interim analysis and one final analysis will be conducted. The objective of the 
interim analysis is to assess assumptions for both the primary effectiveness and primary 
safety endpoints so that sample size can be increased accordingly if necessary. The interim 
analysis will be conducted when 150 patients have completed the 6-month follow up 
procedures, or have experienced treatment failure, or have terminated the study prematurely. 
This is expected to occur at approximately the end of the enrollment period so that additional 
patients can be enrolled should that be recommended based on results from the interim 
analysis.  Patients who have not completed the 3-month blanking period will not be included 
in the interim analysis. Overall type I error will be preserved by down weighting data 
obtained after sample size adjustment, a method first proposed by Cui et al.25 
Based on the estimated treatment success rate and the observed incidence of primary device 
or procedure-related SAEs from each treatment group, conditional power of rejecting the null 
hypothesis at the final analysis will be calculated. Estimated treatment success rate for the 
conditional power calculation will be based on subjects in the Per Protocol population which 
have completed the 9 month effectiveness assessment follow-up period post-blanking or are 
determined to be treatment failures.   
The primary safety endpoint will be estimated using the percentage of subjects with device-
related early-onset primary SAEs (PSAEs) as defined for the primary endpoint at the time of 
the interim analysis.  
Based on the estimated treatment success rate and the observed incidence of primary device 
or procedure-related SAEs from each treatment group, conditional power of rejecting the null 
hypothesis at the final analysis will be calculated. The smallest sample size that ensures 
sufficient conditional power as discussed below for both the primary effectiveness and the 
primary safety endpoints will be recommended. 
The following decision rules will be used by the unblinded statistician to make 
recommendations to the DSMB and sponsor for sample size considerations. 
1. If the conditional power based on observed data is > 80%, continue the study as 
planned. 
2. If the conditional power is < 80%, compute the sample size necessary to increase 
conditional power to ≥ 80%. 
3. If conditional power is < 80% with the maximum sample size (440 subjects), a 
decision will be made jointly by the DSMB and sponsor based on aggregated 
information. Decisions may include the following: 
a) Continue study to enroll the maximum number of subjects (440). 
b) Continue study as planned to enroll a total of 300 subjects (no change). 
c) Discontinue the study. 
  Sample size should ensure sufficient conditional power of both the primary effectiveness 
and the primary safety endpoints. Therefore, the maximum of the two should be 

 
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recommended. The down weighted method by Cui et al25 to preserve type I error will be 
applied independently to the primary effectiveness and primary safety endpoints. 
A.3 
Randomization and Blinding 
Patients will be randomly assigned 1:1 to receive treatment with either the TactiCath Set or 
the control device (NaviStar® ThermoCool® Catheter manufactured by Biosense Webster, 
Inc.) Roll-in patients will not be randomized. Use of 3D mapping equipment will be required 
in both treatment groups. The randomization schedule will be computer generated using a 
permuted block algorithm and will randomly allocate the randomization numbers. The 
randomization numbers will be assigned sequentially through an Interactive Web Response 
System as patients are entered into the study. The randomization schedule will be stratified 
by site. Each site is expected to have approximately 10 to 20 patients. 
All patients will be blinded to treatment assignment. Study personnel, who may be 
unblinded, should not disclose any treatment assignment information to the patient prior to 
unblinding of the study data to all study-related personnel. 
A.4 
Patient Characteristics 
In general, patient demographics and baseline characteristic variables will be summarized 
descriptively by treatment group and overall. Continuous variables will be summarized in 
terms of descriptive statistics including the mean, standard deviation (SD), minimum, 
maximum, and quartiles. Categorical variables will be summarized in terms of frequencies 
and percentages. 
Demographic variables will include age, gender, race, ethnicity, height, and weight. Baseline 
patient characteristics will include the following: 
 Medical history  
 Baseline physical examination and ECG 
 Baseline thyroid and renal function 
 Baseline PT/PTT or INR 
 Baseline and concomitant medication  
 Documentation of arrhythmia events and cardiac medication 
Data collected during the procedure, including activated clotting time and ablation procedure 
data will be summarized. Descriptive statistics for these quantities, including the mean, SD, 
minimum, maximum, and quartiles, will be provided by treatment group. 
The TTE/TEE will be performed at baseline and pre-discharge, and data will be summarized 
in 3 categories: normal, abnormal - not clinically significant, and abnormal - clinically 
significant. 
The remaining patient characteristic variables will be summarized descriptively by treatment 
group and overall (continuous variables: mean, SD, minimum, maximum, and quartiles; 
categorical variables: frequencies and percentages).  

 
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A.5 
Analysis 
A.5.1 
Analysis Populations 
This study will have the following 4 planned analysis populations. 
 The full analysis (FA) population will include all randomized patients. 
 The modified intent-to-treat (MITT) population will include all randomized patients in 
whom a study device was introduced and PVI was attempted. 
 The safety population (SAF) will also include all randomized patients in whom a study 
device was introduced. 
 The per-protocol (PP) population will include all patients in the FA population who do 
not have major protocol deviations that will compromise the effectiveness or safety 
evaluation of the study device. Lists of major protocol deviations and of patients 
excluded from the PP population will be provided prior to database lock and unblinding. 
A.5.2 
Effectiveness 
A.5.2.1 
 Primary Analysis 
The primary effectiveness endpoint of the study is a non-inferiority comparison of treatment 
success assessment as defined by both: 
 Acute procedural success - electrical isolation of all 4 PVs, or in the event of a common PV, 
the clinical equivalent of all PVs, by the end of index procedure (with the device specified by 
the randomization arm) 
 Chronic success – acute procedural success and freedom from recurrence of symptomatic 
AF, AFL, and AT lasting longer than 30 seconds through 9 months of follow-up after a 3 
month blanking period. Re-treatment for AF with ablation or the use of Class I or Class III 
antiarrhythmic drugs after the blanking period constitute a treatment failure.  
The one-sided 95% lower confidence limit will be calculated using the normal approximation 
method for the difference between the 2 treatment groups (Pt - Pc) based on the PP 
population. If the 95% lower confidence limit is > -15%, non-inferiority is demonstrated in 
terms of effectiveness. Median time to treatment failures and probability of treatment failures 
at 12 months will be estimated using the Kaplan-Meier method, and two-sided 95% 
confidence intervals will be provided. Sensitivity analysis will be provided for the FA and 
MITT populations. 
If chronic success is determined to be less than 40% for either the treatment group or the 
control group, additional exploratory analyses on effectiveness outcomes will be performed. 
The analyses will focus on explaining the suboptimal results or poor device performance. 
Effectiveness outcomes (including acute procedural success, chronic success at 12 month, 
free of symptomatic AF after 12 months, free from AF/AFL/AT at 12 month by Holter) will 
be examined by baseline characteristics and by study sites.  Baseline characteristics will 
include age group, relevant medical condition at time of procedure, disease history, 
hypertension and heart failure. Site variation may include experience of operator, experience 

 
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of site, number of operators, percentage of patients who received re-ablation during the 
study, and ablative technique. 
A.5.2.2 
Secondary Analyses 
The following secondary effectiveness endpoints are related to the use of the contact force 
sensor and a formal superiority test will be performed comparing the TactiCath Set to the 
control device using a hierarchically closed test procedure. It is hypothesized that the use of 
the contact force sensor information will result in added procedural effectiveness through a 
reduction of number of electrically reconnected pulmonary veins, time to achieve total PV 
isolation, or total time of RF application. These endpoints will be tested sequentially, 
conditional on the success of reaching the non-inferiority primary effectiveness objective in 
the order they appear below, using a one sided, α = 0.025 test based on the PP population. 
Subsequent endpoints will be tested only if the prior endpoint(s) are superior. 
1. Number of electrically reconnected pulmonary veins following a 30-minute waiting 
period assessed by entrance block 
2. Time to achieve total PV isolation measured from initial application of RF energy to all 
targeted vessels isolated 
3. Total time of RF application required for full PV isolation calculated from data paired 
within investigative site and weighted based on the number of enrollments per site. 
Secondary endpoint one will be tested using the Wilcoxon rank sum test. Secondary 
endpoints 2 and 3 will be tested using the log rank test. Patients without full PV isolation will 
be censored. Sensitivity analysis may be provided for the FA and MITT populations. 
A.5.2.3 
Descriptive Analyses 
The other effectiveness endpoints, listed in Section 6.3.1, will be collected and will be 
summarized descriptively based on the PP population. Continuous variables will be 
summarized in terms of descriptive statistics including the mean, SD, minimum, maximum, 
and quartiles. Categorical variables will be summarized in terms of frequencies and 
percentages. 
A.5.3 
Safety 
The primary safety endpoint is a non-inferiority comparison of device-related early-onset 
primary SAEs between the TactiCath Set and the control device occurring within 7 days of 
the index procedure or hospital discharge, whichever is later, and diagnosed at any time 
during the follow-up period. A complete list of primary SAEs is provided in Table 2.  
Hospitalizations solely due to recurrence of AF/AFL/AT (i.e., without coexisting conditions 
such as thrombo-embolism, worsening of congestive heart failure, etc.) do not count towards 
primary safety. PSAEs that meet the severity criteria described in Table 2 will contribute to 
the primary safety endpoint only in patients in whom a study device (TactiCath or control) 
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The one-sided 95% upper confidence limit will be calculated using the normal approximation 
method for the difference between the two treatment groups (Pt - Pc) based on the SAF 
population. If the 95% upper confidence limit is < 9%, non-inferiority is demonstrated in 
terms of safety. Sensitivity analysis will be provided for the FA and PP populations. 
The secondary safety endpoint includes the incidence of all SAEs during the 12-month 
follow-up period. The secondary safety endpoint will be summarized descriptively based on 
the safety population and all enrolled patients, including the roll-in patients. 
Other safety data, e.g., 12-lead ECG, physical examination, vital signs, NYHA functional 
class, will be collected throughout the study, and will be summarized descriptively based on 
the SAF population. 
A.6 Subgroup Analyses 
In addition to the analyses described in Section A.5, the primary and secondary effectiveness 
and safety endpoints will also be compared between the control group and a subgroup of 
patients from the TactiCath arm whose average contact force during ablation is ≥ 20 g. To 
examine comparability, baseline tables will be displayed showing the contact force 
subgroups (≥ 20 g vs. < 20 g) as well as the overall treatment group.  
The primary effectiveness endpoint and the primary safety endpoint in these subgroups will 
be examined using exploratory statistical analyses and summarized with descriptive 
statistical measures.  Secondary effectiveness and safety endpoints will be analyzed using the 
same methods as described in Section A.5.2.2 and Section A.5.3 and also summarized with 
descriptive statistical measures. No p-values associated with statistical tests or conclusions 
regarding statistical significance of findings will be reported. 
An analysis of primary and secondary endpoints will also be performed by gender subgroups 
(gender analysis). 
 
A.7 Poolability of Data 
The primary justification for poolability across centers is made on the basis that there is a 
uniform study protocol with well-defined inclusion/exclusion criteria and that centers will be 
uniformly monitored to verify protocol compliance. Centers located outside the United States 
have been assessed for participation using the same selection criteria as in the United States 
and will utilize the identical protocol and procedures in their conduct of the study. 
Poolability will be evaluated and justification for pooling data will be provided before 
combining data. Study variables that are potentially related to study endpoints will be 
identified prior to database freeze for the interim analysis, and statistical analysis will 
examine the homogeneity of demographic and procedural covariates across centers and 
geographical regions.  Center effect and interaction between treatment and center will be 
considered in the subgroup analyses and secondary analyses on the primary endpoints to 

 
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examine possible site to site variations using multivariate analysis methods.  A p-value of ≤ 
0.15 will be considered having significant treatment-by-center interaction. The primary 
effectiveness and safety endpoints will be summarized by center.  In these analyses, small 
centers may be combined based on size, center characteristics and geographical 
regions.  Sensitivity analysis will be performed to verify robustness of the statistical model 
by different center pooling algorithms. 
A.8 Missing Data 
For the primary effectiveness analysis, patients who terminated the study prematurely before 
experiencing a treatment failure will not be considered a treatment success at 12 months. 
Patients whose participation in the study is terminated due to reasons clearly unrelated to the 
study device (lost to follow-up due to patient relocation, death due to causes unrelated to the 
study devices, etc.) may also be excluded from the denominator, and thus will not be 
considered treatment failures. An expert medical panel while blinded to the individual 
patient’s treatment arm will adjudicate exclusion of patients from the primary effectiveness 
analysis. The decision will be made prior to obtaining the database snapshot for the interim 
analysis, and prior to database lock for the final analysis.  
Sensitivity analysis will be provided as described below: 
1. All early terminations, regardless of reason for termination will be considered treatment 
failures. 
2. All early terminations, regardless of reasons for termination will be excluded from the 
denominator.  The analysis will be carried out in patients who have either completed the 
12-month follow-up period or have experienced chronic failures. 
3. Worst-case analysis will be used to impute failures for missing observations from the 
TactiCath group and to impute successes for missing observations from the control 
group. 
4. Propensity scores will be used to assess the comparability of the two study groups after 
exclusion of protocol deviations in the PP population. 
5. Tipping point analysis will be used to replace missing data with values so that the p-value 
is equal to significance level. 
For time to treatment failure and probability of treatment failure at 12 months by the 
Kaplan-Meier method, patients who terminated early prior to failure will be censored at time 
of discontinuation and will include all patients. The same rule will apply to the primary 
safety analysis. Patients who terminated the study prematurely without experiencing any 
primary SAEs will not be considered as having any primary SAEs during the course of the 
study. Other missing data will not be imputed. 
Compliance with TTM requirements will be characterized in terms of actual vs. expected 
number of recordings per patient, and overall compliance for each arm of the study. Patients 
with major protocol violations (which may include non-compliance with TTMs) will be 
excluded from the PP population. 
 

 
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APPENDIX B ................................................................................. Principal Investigator 
The principal investigator for the TOCCASTAR study will be 
Vivek Reddy, MD 
Professor of Medicine 
Mount Sinai School of Medicine 
Director, Cardiac Arrhythmia Service 
Mount Sinai Hospital 
One Gustave L Levy Place, Box 1030 
New York, NY 10029 
USA 
 

 
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APPENDIX C ......................................................................... Clinical Events Committee 
The Harvard Clinical Research Institute (HCRI) is a not-for-profit corporation created by the 
Harvard Medical School, Partners Healthcare and the Beth Israel Deaconess Medical Center. 
Contact information is listed below. 
Harvard Clinical Research Institute 
930-W Commonwealth Avenue 
Boston, MA 02215, United States 
1-617-632-1515 
The HCRI has established a standing Clinical Events Committee (CEC) under the guidance 
of the Executive Director of Clinical Investigations, Donald Cutlip, MD. The CEC will be 
responsible for adjudicating all serious adverse events reported during the study, as identified 
and submitted by Endosense, or its designee. 
This committee is comprised of 3 to 5 physicians with experience in clinical trial event 
adjudication, including at least one physician with expertise in each area of the study, who 
are not participants in the study and who meet regularly throughout the study to adjudicate 
events in an ongoing fashion. The CEC members are chosen based on their clinical expertise 
and have no association with any trial for which they adjudicate events. The CEC is blinded 
to treatment assignment during all deliberations. Three voting members comprise a quorum. 
The CEC drafts and agrees upon its working charter for each study prior to performing any 
work. This includes explicit rules outlining the minimum amount of data required, and the 
algorithm followed in order to classify a clinical event. The CEC Administrator will prepare 
the CEC Manual of Operations (MOP) based on this information and the CEC MOP will 
serve as the guideline for adjudication for the specific trial under review. 
Clinical events related to the primary endpoints are identified by the sponsor and submitted 
to HCRI for review. After review of the identified events by HCRI, support documentation 
for identified events is obtained from the site, if necessary, and a summary is written to 
describe the significant details of the event. These summaries, with appropriate support 
documentation, are presented to the physician members of the CEC. The results of the 
adjudications are entered into the Complications database after the CEC meeting. The 
Complications database is specifically created within the overall study database and is used 
in the preparation of DSMB reports, as well as in all analyses of endpoint results. 
CEC meetings are held approximately 3 times per month at HCRI’s offices in Boston, MA. 
As documentation of the CEC meeting and each event under review, HCRI provides to 
Endosense relevant supporting documentation and/or meeting minutes. The format of the 
information will vary depending on whether or not HCRI is involved with event narration. 
 

 
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APPENDIX D ...................................................................Data Safety Monitoring Board 
Premier Research will manage Data Safety and Monitoring Board (DSMB) services for this 
study. Premier Research will generate a DSMB charter, for approval by the DSMB. 
Endosense and Premier Research will identify DSMB members, which will include 3 experts 
in clinical electrophysiology and ablation as voting members as well as a qualified 
statistician and medical monitor as non-voting members. Premier Research will negotiate and 
execute confidentiality and consulting agreements with the members.  
Premier Research will provide a dataset to the statistician who is not a member of the project 
team for analysis. The independent statistician will generate the unblinded tables and listings 
needed for generation of the DSMB report. The report will undergo independent medical 
review by a Premier Research physician before being distributed. 
FDA will be notified in the event that the DSMB recommends any changes to the study 
protocol, procedures or informed consent document. 

 
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APPENDIX E .......................................................................... Core Laboratory Services 
All transtelephonic monitoring (TTM) tracings, 24-hour recordings from Holter monitors, 
and select computed tomography (CT)/magnetic resonance imaging (MRI) scans (those with 
a preliminary finding of moderate (50% – 70%) or severe (> 70%) PV stenosis) will be 
manually over-read by board-certified cardiologists/electrophysiologists at prespecified 
intervals. Findings will be communicated to the investigator and the sponsor. Contact 
information of the TTM and Holter core laboratory is listed below: 
Harvard Clinical Research Institute 
930-W Commonwealth Avenue 
Boston, MA 02215, United States 
1-617-632-1515 
Core laboratory over-read of imaging studies will be provided by: 
Perfuse Core Lab  
Boston Clinical Research Institute 

 
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APPENDIX F .............................................................. Ambulatory Monitoring Services 
Ambulatory monitoring will be conducted by a vendor staffed with qualified caregivers 
including nurses who are trained to accurately elicit patient complaints and physicians who 
perform and approve the reading of ECGs. Subjects are typically issued the transtelephonic 
monitoring (TTM) device when discharged from the hospital after training by the local study 
nurse. They are instructed to transmit an ECG according to a well-defined schedule over the 
next 12 months. They may transmit additional ECGs anytime they experience symptoms. 
The collection of ECG data is accompanied by a report of the patient’s health status and well 
being (including symptoms) obtained over the telephone. 
TTM and Holter services will be provided by: 
 
Agility Centralized Research Services, Inc. 
A CardioNet Company 
2275 Half Day Road 
Suite #133 
Bannockburn, IL 60015  
(847) 374-1260 
 
The Use of Protected Health Information (PHI) by Agility: 
 
Ambulatory monitoring is an integral part of the TOCCASTAR Study Clinical 
Investigational Plan and is essential to the study endpoints. The use of PHI is normally 
provided by patient informed consent strictly for the purpose of compliance with protocol-
defined follow-up. A patient information form is used to provide Agility with the subject’s 
name and telephone contact information should a follow-up call be required. 
 
 Subject information is protected by restricted access to study files via unique user ID 
and passwords for all operators, tracking of all authorized and unauthorized login 
attempts and password expiration schedules. 
 All Agility employees are trained on GCP (Good Clinical Practices) and HIPAA 
(Health Insurance Portability and Accountability Act) guidelines. Training records 
are available upon request. 
 Agility is bound by contract with the study sponsor to protect the privacy and 
confidentiality of all study data and reports. 
 Data subsequently forwarded to investigators, the sponsor and clinical core labs are 
fully de-identified of PHI. 
 Agility will only contact patients directly if a patient has failed to report in a timely 
way or has specifically requested Agility to do so.  
 

 
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APPENDIX G ........................................................ New York Heart Association Classes 
 
NYHA Class 
Criteria 
I 
No symptoms and no limitation in ordinary physical activity. Shortness of 
breath when walking, stair climbing, etc. 
II 
Mild symptoms (mild shortness of breath and/or angina pain) and slight 
limitation during ordinary activity. 
III 
Marked limitation in activity due to symptoms, even during 
less-than-ordinary activity (e.g., walking short distances, approximately 
> 20 – 100 meters). 
Comfortable only at rest. 
IV 
Severe limitations. Experiences symptoms even while at rest, mostly 
bedbound patients. 
Abbreviation: NYHA = New York Heart Association 
 

 
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APPENDIX H .................................................................................Quality of Life Survey 
The Atrial Fibrillation Effect on Quality of Life survey, also known as the AFEQT28 
questionnaire, is a responsive measure of quality of life specifically for atrial fibrillation. It is 
a reliable, validated questionnaire that evaluates Health Related Qualify of Life (HRQoL) 
across three domains:  symptoms, daily activities, and treatment concerns. It is composed of 
20 questions scored on a seven point Likert scale that takes approximately five minutes for 
the subject to complete. The questionnaire is scored for the following results: global AFEQT 
score and subscale functional scores (treatment concerns, daily activities and symptoms.)    
Higher overall AFEQT scores indicate the subject has no limitations while a lower score 
indicates increased to extreme difficulty affect on quality of life due to atrial fibrillation. The 
Treatment Satisfaction Score indicates how well the subject feels their current treatment 
regimen is working, the higher the score, the more satisfied with the treatment. AFEQT will 
be administered to subjects at the baseline visit and at the 12-month post-procedure visit. 
 

 
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APPENDIX I ................................................................................... List of Abbreviations 
3D 
three-dimensional 
ACC 
American College of Cardiology 
ADE 
adverse device effect 
AE 
adverse event 
AF 
atrial fibrillation 
AFEQT 
Atrial Fibrillation Effect on Quality of Life survey 
AFL 
atrial flutter 
AHA 
American Heart Association 
AT 
atrial tachycardia 
CA 
Competent Authority 
CFAE 
complex fractionated atrial electrogram 
CEC 
clinical events committee 
CFR 
Code of Federal Regulations 
CHADS 
congestive heart failure, hypertension, age > 75 years, type 2 diabetes, 
prior stroke or transient ischemic attack 
CIP 
clinical investigational plan 
CRA 
clinical research associate 
CT 
computed tomography 
DSMB 
data safety monitoring board 
ECAS 
European Cardiac Arrhythmia Society 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EHRA 
European Heart Rhythm Association 
ESC 
European Society of Cardiology 
EU 
European Union 
FA 
full analysis 
FDA 
Food and Drug Administration 
FTI 
Force Time Integral 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HCRI 
Harvard Clinical Research Institute 
HRS 
Heart Rhythm Society 
IACUC 
Institutional Animal Care and Use Committee 
ICD 
implantable cardiac defibrillator 
ICE 
intracardiac echocardiography 
IDE 
Investigational Device Exemption 

 
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IEC 
Independent Ethics Committee 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
MI 
myocardial infarction 
MITT 
modified intent-to-treat 
MRI 
magnetic resonance imaging 
NaviStar® 
ThermoCool® 
Catheter 
NaviStar® ThermoCool® open irrigated RF ablation catheter 
NYHA 
New York Heart Association 
PAF 
paroxysmal atrial fibrillation 
PCI 
percutaneous coronary intervention 
PMA 
premarket approval 
PP 
per-protocol 
Premier Research 
Premier Research Group Limited 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
PV 
pulmonary vein 
Q3 2010 
third quarter of calendar year 2010 
Q3 2011 
third quarter of calendar year 2011 
RF 
radiofrequency 
SADE 
serious adverse device effect 
SAE 
serious adverse event 
SAF 
safety 
SD 
standard deviation 
SOP 
Standard Operating Procedure 
TEE 
trans-esophageal echocardiography 
TTE 
trans-thoracic echocardiography 
TTM 
transtelephonic monitoring 
UADE 
unanticipated adverse device effect 
US 
United States 
W 
Watts 
 

 
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APPENDIX J ....................................................................... Supplemental Clinical Study 
 
J.1 
INTRODUCTION 
The TactiCath Set composed of the TactiCath catheter and the TactiSys contact force 
visualization equipment (described in IDE G100230 submitted to FDA on August 13, 2010 
and fully approved on May 17, 2011) is currently being evaluated in the TOCCASTAR 
clinical study. Completion of patient enrollment occurred in June 2012. A total of 317 
subjects (300 randomized and 17 roll-in) have been enrolled at 17 sites. The PMA is 
expected to be ready for submission to FDA in Q3 of 2013. 
In parallel to the IDE evaluation in the United States, the TactiCath Set has been approved 
for commercial use in Europe and in Australia. To date, no device-related complications 
were reported under the applicable post-market vigilance reporting regulatory systems. 
The company has developed a new catheter version along with new contact force 
visualization equipment called the TactiCath Quartz Set, based closely on the TactiCath Set 
devices. The indications for use remain unchanged, as does the catheter basic design. 
Improvements are made to materials and components. This evolution will improve 
manufacturability and increase reliability for the TactiCath catheter. Changes in TactiSys 
will improve usability and integration with the EP lab environment. The company introduced 
the TactiCath Quartz Set in the European market in June 2012. 
To compile evidence of the comparative safety of the TactiCath Quartz Set and to clinically 
evaluate proposed enhancements to the user interface, Endosense proposes to conduct a 
Supplemental Clinical Study with the TactiCath Quartz Set in the US. Clinical data regarding 
acute safety and effectiveness of the TactiCath Quartz Set in patients with PAF will be 
compared to that of the TactiCath Set from the pivotal TOCCASTAR Study to confirm 
comparable clinical performance of the two systems.  
 
J.2 
INTENDED USE AND DEVICE DESCRIPTION 
 
J.2.1 Intended Use of the TactiCath Quartz Set 
The intended use of the TactiCath Quartz Set is the same as the TactiCath Set as described in 
Section 4.1. 
 
J.2.2 Device Description – TactiCath Quartz Set 
The TactiCath Quartz Set developed by Endosense consists of the: 
• 
TactiCath Quartz open irrigated radiofrequency (RF) ablation catheter  
• 
TactiSys Quartz Equipment, the contact force visualization system.  
The TactiCath Quartz Catheter is connected to the TactiSys Quartz Equipment. The TactiSys 
Quartz is connected to a general-purpose computer (PC) on which Endosense TactiSoft 

 
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software will be installed. The TactiSys Quartz Equipment refers to the combination of the 
TactiSys Quartz and TactiSoft. Each of the TactiCath Quartz and TactiSys Quartz Equipment 
has been subjected to full verification and validation.  
 
J.2.3 Functionality of the TactiCath Quartz Set 
The functionality of the TactiCath Quartz Set is identical to the TactiCath Set as described in 
Section 4.2.1. 
 
J.2.4 Evolution from TactiCath Catheter to TactiCath Quartz Catheter 
The basic design from the TactiCath catheter (currently under IDE evaluation) remains 
essentially unchanged. However, a modification of the force sensor has been implemented 
for enhanced stability, reliability and manufacturability. 
The basic design of the TactiCath Quartz body (shaft concept, handle, proximal cable, 
electrical and optical connectors) is equivalent to the current generation TactiCath. Minimal 
changes have been made with respect to functionality and materials that are in direct contact 
with the patient. The manner in which the catheter is used by physicians has not changed.  
The change to the force sensor technology is the main design difference between the 
TactiCath and the TactiCath Quartz. Modifications to the force sensor include: 
• 
Fabry-Pérot technology replaces Fiber Bragg Grating (FBG) technology  
• 
Material of force sensor support (deformable body) changed from plastic (Liquid 
Crystal Polymer) to metallic (titanium) 
• 
Force sensor is reduced in length from 4 mm to 1.5 mm and positioned closer to 
electrode 1 (tip) 
The new force sensor allows precise real-time measurement of the force applied by the distal 
tip of the catheter to the heart wall with a resolution and sensitivity of about 1 gram. The 
principle of operation still consists of measuring the deformation of a deformable body in 
response to the force. This deformation is now measured by displacement sensors (Fabry-
Pérot technology) instead of FBG strain sensors. Three displacement sensors are mounted 
circumferentially to the deformable body. These changes to the force sensor technology have 
no impact on the clinical performance of the device other than to improve reliability and the 
resolution of CF data. 
 
J.2.5 Evolution from TactiSys to TactiSys Quartz Equipment 
The TactiSys Quartz Equipment is indicated for use in conjunction with an Endosense 
TactiCath Quartz Contact Force Ablation Catheter. The TactiSys Quartz Equipment allows 
the visualization of the CF information coming from the catheter tip. 
The contact force visualization equipment has been redesigned to be compatible with the 
new choice of Fabry-Pérot force sensing technology incorporated in the TactiCath Quartz 

 
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Catheter. The two hardware components, the Base Station and Splitter of the current 
generation equipment TactiSys, have been replaced by only one hardware component in the 
TactiSys Quartz. 
The TactiSys Quartz Equipment is composed of the TactiSys Quartz device and TactiSoft 
software. The TactiSoft software, which had been incorporated in the Base Station, now 
becomes stand-alone software running on a PC.  
TactiSys Quartz 
The TactiSys Quartz includes the main signal processing unit and the optical measurement 
system. TactiSys Quartz acts as a server, which can send the contact force information to 
clients, either a PC running Endosense’s TactiSoft software, or another device, or both at the 
same time. 
The TactiSys Quartz has a dedicated power supply. As the principal signal processing unit, 
TactiSys Quartz hosts the software (called TactiSys Quartz Software) to collect data from the 
catheter to compute the force and the related information. The TactiSys Quartz shares this 
information with the clients via a TCP-IP protocol through an Ethernet connection. 
In addition to sharing force information with other devices, the new configuration offers the 
advantage of measuring the contact force closer to the patient, therefore obviating the optical 
and electrical connections currently used in TactiSys between Base Station and Splitter. The 
optical measurement system allows a higher sampling rate (50Hz) resulting in improved 
resolution of force signals and a better algorithm to compensate for drift. Another advantage 
of this technology is that the in-situ calibration procedure of the catheter is no longer needed. 
The diagram below shows the TactiSys Quartz Equipment architecture, with the software 
items and interfaces between them. It also includes the TactiSoft software running on a PC, 
and the device communicating with the TactiSys Quartz. 
Figure 2 TactiCath Quartz Set Overview 
 
TactiSoft 
TactiSoft v4 is the software designed by Endosense to display the force information received 
from the TactiSys Quartz. The TactiSoft software will be available on CD for installation on 

 
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a general-purpose computer (non-medical grade) that fulfills specific configuration 
requirements. For the Supplemental Clinical Study, the general purpose computer will be 
provided by Endosense and will communicate with the TactiSys Quartz through an Ethernet 
connection. 
TactiSoft v4 will essentially have the same display functionalities as current TactiSoft v3.2, 
with enhanced options for user customization. Several new diagnostic features have been 
introduced that may be optionally activated as part of the user customization. 
Figure 3 Procedure Screen Example TactiSoft v3.2 (right) and v4.3 (left) 
 
 
 
 
 
 
 
 
 
J.3 
STUDY PURPOSE AND OBJECTIVES 
 
J.3.1 Study Purpose 
The purpose of the Supplemental Clinical Study is to evaluate the acute clinical safety and 
effectiveness of the TactiCath Quartz Set to verify that the new design performs comparably 
to the initial design. 
The TactiCath Quartz Set includes hardware design modifications intended to improve 
manufacturability and to increase reliability as well as minor enhancements to the user 
interface intended to promote improved usability and safety. These enhancements do not 
introduce any new design features that would be expected to measurably impact clinical 
performance compared with the original design.  
 
J.3.2 Study Objectives 
 
J.3.2.1 Effectiveness 
To provide comparative acute effectiveness data on the treatment of symptomatic PAF 
relative to the TactiCath Set. 
 

 
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J.3.2.2 Safety 
To provide comparative acute safety data on the incidence of early-onset SAEs relative to the 
TactiCath Set. 
 
J.4 
STUDY ENDPOINTS 
Outcomes from the Supplemental Clinical Study will be summarized descriptively.  
  
J.5 
STUDY DESIGN 
 
J.5.1 Justification for the Investigation 
The main objective of the Supplemental Clinical Study will be to provide confirmatory 
evidence regarding the acute safety and effectiveness of the TactiCath Quartz Set in patients 
with symptomatic PAF. In principle, the TactiCath Quartz Set will provide the same 
therapeutic and diagnostic functionality to the operator during use as the TactiCath Set. It is 
anticipated that the risks and benefits will also be the same. The new device will be evaluated 
in an identical patient population (inclusion and exclusion criteria), using the same 
procedural methodology from the TOCCASTAR study. 
Prior to first clinical use, a comprehensive verification and validation study will confirm the 
operation and robustness of the new features included in the device. 
Given the similarities in patient populations, device functionality, and procedural testing 
requirements, the acute procedural and 30 day safety data from the TactiCath Quartz Set may 
be compared with data from the TactiCath Set. Therefore, a minimum of 30 days of follow-
up data on 50 subjects will be submitted for FDA review in the original PMA, plus any 
additional follow- up data available at the time of submission. Subjects enrolled in the 
supplemental study will comply with the same extended follow-up requirements from the 
original study (every 6 months until PMA approval) to provide additional safety and 
effectiveness data from the post-assessment period through PMA approval. 
 
J.5.2 Scope of Study 
Up to 10 sites participating in the TOCCASTAR Study will be asked to also participate in 
the Supplemental Clinical Study. Investigators will likewise be chosen from the current 
group of TOCCASTAR investigators. Sites will be required to seek approval of the Clinical 
Investigational Plan and Patient Informed Consent (Version F) as a prerequisite to 
enrollment.  
Up to 50 subjects will be enrolled in a non-randomized manner and treated identically to the 
roll-in patient population except as described in Section J.7.  
 
J.5.3 Study Assessment Intervals 

 
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For the purpose of assessing acute comparative performance, patients will be followed for a 
minimum of 30 days, after which subjects will continue follow-up according to the Schedule 
of Activities (Table 1) with one exception. To comply with current standard of care at the 
participating institutions, CT and MR scans are recommended but not required for the 
supplemental study patients only. 
The supplemental study is intended to provide confirmation that the device and procedure 
related complications assessed at 30 days are comparable to the experience with the 
randomized TactiCath subjects. The supplemental study also allows for subjects to be 
followed for a total of 12 months (3 months blanking period followed by 9 month 
effectiveness assessment period).  
 
J.5.4 Clinical Investigational Plan 
We propose to study the primary safety and acute effectiveness of the TactiCath Quartz Set 
in the Supplemental Clinical Study with the following key features (relative to the current 
randomized study): 
• 
Single arm, non-randomized study  
• 
Identical inclusion and exclusion criteria for subjects  
• 
Identical procedural testing requirements during the index procedure  
• 
Identical data collection requirements in the acute study phase  
• 
Identical follow-up requirements for 12 month (excluding CT/MR scans) 
• 
30 day safety outcome assessment on 50 patients (descriptive summary comparing 
randomized and supplemental study subjects)  
• 
Extended follow-up every 6 months until time of PMA approval  
• 
Study restricted to sites who are already participating in the TOCCASTAR Study  
 
 
J.6 
CRITERIA FOR ELIGIBILITY 
Subject eligibility is identical to the initial randomized study as described in Section 8 
CRITERIA FOR ELIGIBILITY. 
 
 
J.7 
STUDY PROCEDURES 
Procedures required in the Supplemental Clinical Study are identical to those specified in 
Section 10 STUDY PROCEDURES of the randomized study with the following exceptions: 
1. Subjects enrolled in the Supplemental Clinical Study will not be randomized. All 
subjects will be treated with the TactiCath Quartz Set. 

 
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2. CT and/or MR scans are recommended but not required (either pre-procedure or at 3-
month follow-up). 
 
 
J.8 
PATIENT BENEFITS AND RISKS 
Benefits and risks are identical to those described in Section 11 except for those risks that 
have been reduced by the elimination of the CT and MR scans in the study. In addition, the 
TactiCath Set continues to be used safely in a commercial setting outside of the US having 
now exceeded 2500 units worldwide. Data resulting from both company and investigator 
sponsored research has resulted in over 30 peer reviewed publications and presentations that 
have reported on potential benefits associated with contact force sensing with TactiCath. 
 
J.9 
ADVERSE EVENTS 
The definitions and reporting requirements related to adverse events, serious adverse events 
and UADEs are identical to those described in Section 12. Only serious adverse events 
related to safety will be referred to the Clinical Events Committee for adjudication for 
subjects enrolled in the Supplemental Clinical Study. I.e., arrhythmia recurrence resulting in 
a “treatment failure” will not be adjudicated for an effectiveness endpoint determination.  
 
J.10 
OMISSIONS 
Unless specifically described in APPENDIX J, all other aspects of study conduct in the 
Supplemental Clinical Study will be the same as in the initial randomized study as described 
in the body and appendices of this Clinical Investigational Plan. 
 
 

 
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APPENDIX K ............................................................................. Continued Access Study 
 
K.1 
INTRODUCTION 
The TactiCath Quartz Set PMA was submitted to FDA in Q4 of 2013. While the marketing 
application is under regulatory review, St Jude Medical proposes to conduct a Continued 
Access Study of the TactiCath Quartz Set in the US.  The study will report clinical data 
regarding acute safety and effectiveness of the TactiCath Quartz Set in patients with PAF. 
 
K.2 
DEVICE DESCRIPTION 
The TactiCath Quartz Catheter and TactiSys Quartz Equipment are described in Section J.2 
above. Changes to the TactiSoft Graphical User Interface (GUI) software are described in 
Section K.2.1 below. 
 
K.2.1 TactiSoft Software 
TactiSoft v4.3.1.0 will be used in the Continued Access Study. It is essentially the same as 
v4.3.0.0 that was used in the Supplemental Clinical Study as shown in Figure 4. The main 
functionalities are identical, however several minor modifications were made to conform to 
findings from a Usability Study of human factors of the user interface. 
 
Figure 4 Procedure Screen Example TactiSoft v4.3.0.0 (left) and 4.3.1.0 (right) 
 
 
Changes implemented in the TactiSoft v4.3.1.0 GUI include: 
“Please check baseline” message appearance frequency reduced: 
This message appears in response to the detection of a possible offset in the contact 
force reading. In an engineering study, it was found that the threshold for detection 
could be safely reduced to improve specificity (thereby avoiding false positives) 
without compromising the detection of true positive offsets. 

 
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“Please check baseline” message replaced with “Please reset baseline” upon initial use: 
An initial baseline reset is required upon first use of a TactiCath catheter. The “please 
check baseline” message that appeared was identical to the message that might appear 
during later use for different reasons and may have contributed to a user error. The 
new message has been implemented to clarify the initialization requirement that 
should improve user comprehension and recognition. (See example below.) 
Figure 5 “Please reset baseline” message 
 
 
 
 
 
 
 
 
 
 
 
TactiSoft v4.3.0.0 
TactiSoft v4.3.1.0 
 
 
“Please check irrigation” message replaced with “Please check baseline”: 
In the previous TactiCath catheter design, an irrigation failure could cause a force 
drift during ablation causing the “Please check irrigation” message to appear in 
response. Owing to design improvements in the current version of the catheter, 
irrigation failure during ablation will no longer cause a drift in the contact force. To 
avoid user error and mitigate the risk of delayed therapy caused by a catheter change, 
the irrigation message has been replaced by the more appropriate “Please check 
baseline” message.  
  
“Settings” menu - Improved wording and button operation: 
The summative usability test revealed common user errors associated with navigating 
the settings screens due to ambiguous labels and inconsistent up/down button 
behavior. The wording and operation of certain buttons and labels have been 
improved to better correlate with the button function. (See example below.) 
 
 

 
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Figure 6 Settings Menu 
 
 
 
 
 
 
 
 
 
 
 
 
TactiSoft v4.3.0.0 
TactiSoft v4.3.1.0 
 
Use of pictograms in procedure screen:  
This change has been implemented as an additional change beyond the opportunities 
of improvement identified during usability testing. The primary intention of this 
change was to improve readability of the contact force information displayed and to 
better group numerical and graphical contact force indicators, respectively. The 
addition of pictograms instead of words or letters allows the use of a uniform user 
interface in the multilingual international environment, especially with respect to 
contact force reading and stability indicator in the TactiSoft procedure screen. 
 
K.3 
STUDY PURPOSE AND OBJECTIVES 
 
K.3.1 Study Purpose 
The purpose of the Continued Access Study is to provide access to the TactiCath Quartz Set 
during the regulatory review period to collect confirmatory evidence of safety and 
effectiveness. 
 
K.3.2 Study Objectives 
 
K.3.2.1 
Effectiveness 
To collect acute effectiveness data on the treatment of symptomatic PAF with the TactiCath 
Quartz Set. 
 

 
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To collect chronic effectiveness data on the treatment of symptomatic PAF with the 
TactiCath Quartz Set. 
 
K.3.2.2 
Safety 
To collect acute safety data on the incidence of early-onset SAEs relative to the TactiCath 
Quartz Set. 
 
K.4 
STUDY ENDPOINTS 
Outcomes from the Continued Access Study will be summarized descriptively.  
  
K.5 
STUDY DESIGN 
 
K.5.1 Justification for the Investigation 
The Continued Access Protocol will provide ongoing physician access to the TactiCath 
Quartz Set and its use under the same indication to provide confirmatory evidence of the 
safety and effectiveness of the TactiCath Quartz Set in patients with symptomatic PAF.  
 
K.5.2 Scope of Study 
Up to 10 sites in the US currently participating in the TOCCASTAR Study will be invited to 
participate in the Continued Access Study. Investigators will likewise be chosen from the 
current group of investigators. Sites will be required to seek approval of the Clinical 
Investigational Plan and Patient Informed Consent (Version H) as a prerequisite to 
enrollment.  
Up to 150 subjects will be enrolled in a non-randomized manner and treated identically to the 
Supplemental Clinical Study population except as described in Section K.7.  
 
K.5.3 Study Assessment Intervals 
The Continued Access study is intended to provide confirmation that the device is safe and 
effective for the treatment of PAF in subjects followed for a total of 12 months (3 months 
blanking period followed by 9 month effectiveness assessment period).  
 
K.5.4 Clinical Investigational Plan 
We propose to study the primary safety and acute effectiveness of the TactiCath Quartz Set 
in the Continued Access Study with the following key features (relative to the TOCCASTAR 
study): 

 
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• 
Single arm, non-randomized study  
• 
Identical inclusion and exclusion criteria for subjects  
• 
Identical procedural testing requirements during the index procedure  
• 
Identical data collection requirements in the acute study phase  
• 
Follow-up requirements do not include CT/MR scans and TTM monitoring.  
• 
Safety and Efficacy outcomes reported descriptively  
• 
Study restricted to sites who are already participating in the TOCCASTAR Study  
 
K.6 
CRITERIA FOR ELIGIBILITY 
Subject eligibility is identical to the initial randomized study as described in Section 8 
CRITERIA FOR ELIGIBILITY. 
 
K.7 
STUDY PROCEDURES 
Procedures required in the Continued Access Study are identical to those specified in Section 
10 STUDY PROCEDURES with the following exceptions: 
1. Subjects enrolled in the Continued Access Study will not be randomized. All subjects 
will be treated with the TactiCath Quartz Set. 
2. Subjects enrolled in the Continued Access Study will not receive ambulatory 
monitoring via TTM devices. TTM monitoring is replaced by 48-hour holter 
recordings at 3- and 6-months post procedure, and 72-hour holter recording at 12-
months post procedure. 
3. CT and/or MR scans are recommended but not required (either pre-procedure or at 3-
month follow-up). 
4. Subjects may take previously failed antiarrhythmic medications after the blanking 
period. 

 
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Table 4 Schedule of Activities for Continued Access Study 
 
 
 
Baseline 
Procedure 
Pre-
discharge 
7 days 
± 2 days 
Telephone 
3 months 
± 2 weeks 
6 months 
± 3 weeks 
12 months 
± 3 weeks 
Extended 
every 6 mos 
± 4 weeks 
Informed consent 
X 
 
 
 
 
 
 
 
Inclusion/exclusion 
X 
 
 
 
 
 
 
 
Documentation of PAF episodes 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Thyroid and renal function (standard practice) 
X 
 
 
 
 
 
 
 
PT/PTT or INR 
X 
 
X 
 
 
 
 
 
Physical examination,vital signs, height, weighta 
X 
 
X 
 
X 
X 
X 
 
Pregnancy test (women of childbearing potential) 
X 
 
 
 
 
 
 
 
12-lead ECG 
X 
 
X 
 
X 
X 
X 
 
Cardiac medications 
X 
 
X 
X 
X 
X 
X 
 
NYHA functional class 
X 
 
 
 
X 
X 
X 
 
Quality of life survey 
X 
 
 
 
 
 
X 
 
Activated clotting time  
 
X 
 
 
 
 
 
 
Ablation procedure data 
 
X 
 
 
 
 
 
 
Force Sensing data  
 
X 
 
 
 
 
 
 
Arrhythmia events 
X 
 
X 
X 
X 
X 
X 
 
Adverse events 
 
X 
X 
X 
X 
X 
X 
Xf 
Protocol deviation 
X 
X 
X 
X 
X 
X 
X 
 
TEE (ICE)b 
X 
(X) 
 
 
 
 
 
 
TTE (recommended)c 
X 
 
(X) 
 
 
 
 
 
CT or MRI scand 
X 
 
 
 
X 
 
 
 
Holter monitoringe 
 
 
 
 
X 
X 
X 
 
Arrhythmia history 
 
 
 
 
 
 
 
X 
Abbreviations: CT = computed tomography; ECG = electrocardiogram; INR = international normalized ratio; MRI = magnetic resonance imaging; NYHA = New 
York Heart Association; PAF = paroxysmal atrial fibrillation; PT = prothrombin time; PTT = partial thromboplastin time; TEE = trans-esophageal echocardiography; 
ICE = intra-cardiac echocardiography. NOTES: a.Weight and height will be assessed at baseline only. b.TEE within 24 hrs or ICE at time of procedure to exclude 
atrial thrombus. c.TTE within 6 mos to measure left atrial dimension. Recommended within 24 hrs post procedure to exclude pericardial effusion. d.Not required for 
CAP study subjects. If evidence of stenosis is seen at 3 mos, the investigator may prescribe additional serial scans. e.48 hour Holter recording at 3, 6 months and 72 
hour recording at 12 months. f.survival and hospitalizations only. 

 
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K.8 
PATIENT BENEFITS AND RISKS 
Benefits and risks are identical to those described in Section 11 except for those risks that 
have been reduced by the elimination of the TTM in the study. These risks are somewhat 
offset by the increased holter monitoring at 3, 6, and 12 months post-procedure. In addition, 
the TactiCath Quartz Set continues to be used safely in a commercial setting outside of the 
US having now exceeded 1500 units worldwide. Data resulting from both company and 
investigator sponsored research has resulted in over 30 peer reviewed publications and 
presentations that have reported on potential benefits associated with contact force sensing 
with TactiCath. 
 
K.9 
ADVERSE EVENTS 
The definitions and reporting requirements related to adverse events, serious adverse events 
and UADEs are identical to those described in Section 12. Adverse Events will be reported to 
St Jude Medical.   
 
K.10 CLINICAL EVENTS COMMITTEE 
A successor Clinical Events Committee (CEC) will be created to assume responsibility for 
reviewing all Serious Adverse Events reported in the Continued Access Study. This 
committee is comprised of 3 to 5 physicians with experience in clinical trial event 
adjudication, including at least one physician with expertise in each area of the study, who 
are not participants in the study and who meet regularly throughout the study to adjudicate 
events in an ongoing fashion. The CEC members are chosen based on their clinical expertise 
and have no association with any trial for which they adjudicate events. The CEC is blinded 
to treatment assignment during all deliberations. Three voting members comprise a quorum. 
The CEC drafts and agrees upon its working charter for each study. This includes explicit 
rules outlining the minimum amount of data required, and the algorithm followed in order to 
classify a clinical event. A CEC Manual of Operations (MOP) is prepared based on this 
information and the CEC MOP will serve as the guideline for adjudication for the specific 
trial under review. 
Only serious adverse events related to safety will be referred to the Clinical Events 
Committee (CEC) for adjudication for subjects enrolled in the Continued Access Study, i.e. 
arrhythmia recurrence resulting in a “treatment failure” will not be adjudicated for an 
effectiveness endpoint determination. 
K.11 PROTOCOL DEVIATIONS 
Deviations from the Continued Access Protocol will be reported to St Jude Medical via 
eCRF. 
K.12 AMBULATORY MONITORING 

 
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Ambulatory monitoring via Holter monitors will be provided and over-read by a qualified 
vendor or core lab to ensure quality of monitors and readings. 
K.13 OVERSIGHT 
Data management and monitoring of conduct for the Continued Access Study will be the 
responsibility of St. Jude Medical.  Clinical investigator agrees to permit St Jude Medical, 
and its representatives, access to all clinical supplies, source documents, study data, eCRF 
and other study documents. St. Jude Medical assumes the right to discontinue the study for 
safety or administrative purposes. St. Jude Medical also assumes all rights regarding use of 
information and publication. 
K.14 OMISSIONS 
Unless specifically described in APPENDIX K, all other aspects of study conduct in the 
Continued Access Study will be the same as in the TOCCASTAR study as described in the 
body and appendices of this Clinical Investigational Plan.