Clinical Trial to Evaluate Cardiovascular Outcomes In Patients Treated With the Tricuspid Valve Repair System Pivotal
Phase: NA
Conditions: Tricuspid Regurgitation
Sponsor: Abbott Medical Devices

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 1 of 136 
 
  
  
 
 
 
Clinical TRIal to EvaLUate Cardiovascular 
OutcoMes IN PAtients Treated with the 
Tricuspid ValvE Repair System Pivotal 
(TRILUMINATE Pivotal) 
Protocol #: ABT-CIP-10249 
 
 
 
 
 
 
Sponsor: Abbott 
 
 
 
 
Version F 
June 30th, 2022 
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 4 of 136 
NATIONAL COORDINATING CLINICAL INVESTIGATOR / STUDY PRINCIPAL 
INVESTIGATOR SIGNATURE PAGE 
 
 
 
 
I have read and agree to adhere to the clinical investigation plan and all regulatory requirements 
applicable in conducting this clinical investigation. 
 
 
[Coordinating Clinical Investigator / Study Principal Investigator] 
 
Printed name: 
Signature: 
Date: 
 
Printed name: 
Signature: 
Date: 
 
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 5 of 136 
SITE PRINCIPAL INVESTIGATOR SIGNATURE PAGE 
 
 
 
I have read and agree to adhere to the clinical investigation plan and all regulatory requirements 
applicable in conducting this clinical investigation. 
 
 
Site Principal Investigator 
 
Printed name: 
Signature: 
Date: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 6 of 136 
 TABLE OF CONTENTS  
  
Table of Contents 
1 
INTRODUCTION ................................................................................................................. 18 
2 
BACKGROUND AND RATIONALE ..................................................................................... 18 
2.1 
Background .................................................................................................................. 18 
2.1.1 
Tricuspid Regurgitation Description and Etiology .................................................. 18 
2.1.2 
MitraClip® Experience in Treatment of Mitral Regurgitation ................................. 20 
2.1.3 
MitraClip® Experience in Tricuspid Regurgitation ................................................. 21 
2.1.4 
TriClipTM Experience .............................................................................................. 22 
2.2 
Rationale for Conducting this Clinical Investigation ...................................................... 23 
3 
CLINICAL INVESTIGATION OVERVIEW ........................................................................... 24 
3.1 
Clinical Investigation Objective ..................................................................................... 24 
3.2 
Device To Be Used in the Clinical Investigation ........................................................... 24 
3.2.1 
Name of the Device Under Investigation ............................................................... 24 
3.2.2 
Intended Indication for Use ................................................................................... 26 
3.2.3 
Description of the Device Under Investigation (TriClip) ......................................... 26 
3.2.4 
Summary of Preclinical Studies ............................................................................. 28 
3.2.5 
Device Handling .................................................................................................... 28 
4 
CLINICAL INVESTIGATION DESIGN ................................................................................. 28 
4.1 
Clinical Investigation Procedures and Follow-up Schedule .......................................... 31 
4.2 
Measures Taken to Avoid and Minimize Bias ............................................................... 31 
4.2.1 
Subject Recruitment and Randomization .............................................................. 31 
4.2.2 
Maintaining Similar Levels of Follow-up ................................................................ 31 
4.2.3 
Administration of Assessments ............................................................................. 32 
4.2.4 
Eligibility Committee (EC) ...................................................................................... 32 
4.2.5 
Review of Echocardiography Images .................................................................... 32 
4.2.6 
Safety and Effectiveness Monitoring ..................................................................... 32 
4.2.7 
Follow-Up Compliance .......................................................................................... 32 
4.3 
Continued Access Study Procedures and Follow-up Schedule.................................... 33 
4.4 
Suspension or Early Termination of the Clinical Investigation ...................................... 33 
5 
ENDPOINTS ........................................................................................................................ 34 
5.1 
Randomized Cohort ...................................................................................................... 34 
5.1.1 
Primary Endpoint ................................................................................................... 34 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
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5.1.2 
Powered Secondary Endpoints ............................................................................. 35 
5.1.3 
Descriptive Endpoints ............................................................................................ 35 
5.2 
Single-arm Cohort ........................................................................................................ 36 
5.2.1 
Primary Endpoint ................................................................................................... 36 
5.2.2 
Secondary Endpoints ............................................................................................ 37 
5.2.3 
Descriptive Endpoints ............................................................................................ 37 
5.3 
Imaging Sub-Study Endpoints ...................................................................................... 38 
5.4 
Health Economic Data .................................................................................................. 39 
6 
SUBJECT SELECTION AND WITHDRAWAL ..................................................................... 39 
6.1 
Subject Population ........................................................................................................ 39 
6.2 
Subject Screening and Informed Consent .................................................................... 39 
6.2.1 
Subject Screening ................................................................................................. 39 
6.2.2 
Informed Consent .................................................................................................. 40 
6.3 
Eligibility Criteria ........................................................................................................... 42 
6.3.1 
Inclusion Criteria .................................................................................................... 42 
6.3.2 
Exclusion Criteria .................................................................................................. 42 
6.4 
Subject Enrollment ....................................................................................................... 44 
6.4.1 
Enrollment of Medicare Beneficiaries .................................................................... 44 
6.4.2 
Historically Under-Represented Demographic Subgroups .................................... 44 
6.5 
Subject Withdrawal ....................................................................................................... 45 
6.6 
Total Expected Duration of the Clinical Investigation ................................................... 46 
6.7 
Expected Duration of Each Subject’s Participation ...................................................... 46 
6.8 
Number of Subjects ...................................................................................................... 46 
6.9 
Estimated Time Needed to Select Required Number of Subjects ................................ 47 
7 
TREATMENT AND EVALUATION OF ENDPOINTS........................................................... 47 
7.1 
Eligibility Committee Review ........................................................................................ 47 
7.2 
Roll-in Subjects ............................................................................................................. 47 
7.3 
Baseline ........................................................................................................................ 47 
7.3.1 
Baseline Clinical Assessments .............................................................................. 47 
7.4 
Randomization .............................................................................................................. 48 
7.5 
Blinding ......................................................................................................................... 48 
7.6 
Index Procedure (Roll-In, Device Group and Single-arm Cohort) ................................ 48 
7.6.1 
Subject Preparation ............................................................................................... 48 
7.6.2 
Pre-Procedure ....................................................................................................... 49 

TRILUMINATE Pivotal CIP 
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Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
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7.6.3 
TriClipTM Device Placement Procedure ................................................................. 50 
7.6.4 
Post-Implant .......................................................................................................... 51 
7.7 
Post-procedure (Roll-in, Device Group and Single-arm Cohort; In-hospital) ................ 51 
7.8 
Discharge (Roll-in, Device Group and Single-arm Cohort) ........................................... 51 
7.8.1 
Post-Procedure Medications ................................................................................. 52 
7.9 
“Treatment” Visit (Control Group) ................................................................................. 53 
7.10 
Follow-up Assessments ................................................................................................ 53 
7.10.1 
Follow-up CIP Medications .................................................................................... 53 
7.10.2 
Follow-up for All Subjects ...................................................................................... 53 
7.11 
TriClipTM Intervention in Control Group Subjects or Additional TriClipTM Intervention in 
Roll-in, Device Group or Single-arm Cohort Subjects ............................................................. 54 
7.12 
Tricuspid Valve Surgery ............................................................................................... 55 
7.12.1 
30-Day Post-Tricuspid Valve Surgery Follow-up ................................................... 55 
7.13 
Explanted TriClipTM Device ........................................................................................... 55 
7.14 
Patient Reported Outcome (PRO) Measures ............................................................... 55 
7.15 
Schedule of Events ....................................................................................................... 57 
8 
ADVERSE EVENTS ............................................................................................................ 58 
8.1 
Definition ....................................................................................................................... 58 
8.1.1 
Adverse Event ....................................................................................................... 58 
8.1.2 
Serious Adverse Event .......................................................................................... 58 
8.1.3 
Device Deficiency/Device Malfunction .................................................................. 58 
8.2 
Device Relationship ........................................................ Error! Bookmark not defined. 
8.2.1 
Unanticipated (Serious) Adverse Device Effect [U(S)ADE] .... Error! Bookmark not 
defined. 
8.3 
Adverse Event and Device Deficiency/Device Malfunction Reporting .......................... 59 
8.3.1 
Adverse Event Reporting ...................................................................................... 59 
8.3.2 
Unanticipated Serious Adverse Device Effect Reporting to Sponsor and IRB ...... 60 
8.3.3 
Device Deficiency/Malfunction Reporting .............................................................. 60 
8.3.4 
Adverse Event Reporting to Country Regulatory Authorities by the Sponsor ....... 61 
9 
STATISTICAL CONSIDERATIONS ..................................................................................... 61 
9.1 
Analysis Populations .................................................................................................... 61 
9.1.1 
Randomized Cohort .............................................................................................. 61 
9.1.2 
Single-arm Cohort ................................................................................................. 62 
9.2 
Statistical Analyses ....................................................................................................... 62 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
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9.2.1 
Randomized Cohort .............................................................................................. 62 
9.2.2 
Single-arm Cohort ................................................................................................. 65 
9.3 
Sample Size Calculation and Assumptions .................................................................. 68 
9.3.1 
Randomized Arm Cohort ....................................................................................... 68 
9.3.2 
Single-arm Cohort ................................................................................................. 68 
9.4 
Timing of Analysis ........................................................................................................ 69 
9.5 
Subgroup Analysis ........................................................................................................ 70 
9.6 
Multiplicity ..................................................................................................................... 70 
9.7 
Procedures for Accounting for Missing Data ................................................................ 70 
9.8 
Sample Size Re-estimation .......................................................................................... 70 
9.9 
Statistical Criteria for Termination ................................................................................ 70 
9.10 
Success Criteria ........................................................................................................... 70 
9.11 
Deviations from Statistical Plan .................................................................................... 71 
10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ...................................................... 71 
11 QUALITY CONTROL AND QUALITY ASSURANCE .......................................................... 71 
11.1 
Selection of Clinical Sites and Investigators ................................................................. 71 
11.2 
Site Principal Investigator Responsibilities ................................................................... 71 
11.3 
Clinical Investigation Finances and Agreements .......................................................... 71 
11.4 
CIP Amendments ......................................................................................................... 72 
11.5 
Training ......................................................................................................................... 72 
11.6 
Monitoring ..................................................................................................................... 72 
11.7 
Deviations from CIP ...................................................................................................... 73 
11.8 
Quality Assurance Audit ............................................................................................... 73 
11.9 
Committees .................................................................................................................. 73 
11.9.1 
Steering Committee ............................................................................................... 73 
11.9.2 
Publications Committee ......................................................................................... 74 
11.9.3 
Data Monitoring Committee (DMC) ....................................................................... 74 
11.9.4 
Clinical Events Committee (CEC) ......................................................................... 74 
11.9.5 
Eligibility Committee .............................................................................................. 74 
11.9.6 
Imaging Committee ............................................................................................... 75 
12 DATA HANDLING AND RECORD KEEPING ..................................................................... 75 
12.1 
Protection of Personally Identifiable Information .......................................................... 75 
12.2 
Data Management Plan ................................................................................................ 76 
12.3 
Source Documentation ................................................................................................. 76 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
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12.4 
Case Report Form Completion ..................................................................................... 76 
12.5 
Record Retention .......................................................................................................... 77 
12.6 
Investigational Devices Accountability (Applicable for US and Canada Only).............. 77 
13 ETHICAL CONSIDERATION ............................................................................................... 77 
13.1 
Institutional Review Board/Medical Ethics Committee Review and Approval ............... 77 
14 CLINICAL INVESTIGATION CONCLUSION ....................................................................... 78 
15 PUBLICATION POLICY ....................................................................................................... 78 
16 RISK ANALYSIS .................................................................................................................. 78 
16.1 
Anticipated Clinical Benefits ......................................................................................... 78 
16.2 
Foreseeable Adverse Events and Anticipated Adverse Device Effects ........................ 79 
16.3 
Residual Risks Associated with the Device Under Investigation, as Identified in the 
Risk Analysis Report ............................................................................................................... 79 
16.4 
Risks Associated with Participation in this Clinical Investigation .................................. 79 
16.5 
Possible Interactions with Protocol-Required Concomitant Medications (if applicable) 79 
16.6 
Steps Taken to Control or Mitigate Risks ..................................................................... 80 
16.7 
Risk to Benefit Rationale .............................................................................................. 80 
17 APPENDIX I: ABBREVIATIONS AND ACRONYMS ........................................................... 81 
18 APPENIX II: DEFINITIONS ................................................................................................. 83 
19 APPENDIX III: SITE CONTACT INFORMATION ................................................................ 96 
20 APPENDIX IV: REFERENCES ............................................................................................ 97 
21 APPENDIX V: RATES OF FORSEEABLE ADVERSE EVENTS ......................................... 99 
22 APPENDIX VI: LABELS ..................................................................................................... 103 
23 APPENDIX VII: CASE REPORT FORMS ......................................................................... 104 
24 APPENDIX VIII: INFORMED CONSENT FORM ............................................................... 105 
25 APPENDIX IX: MONITORING PLAN ................................................................................ 106 
26 APPENDIX X: Transthoracic Echo (TTE) Protocol ............................................................ 107 
27 APPENDIX XI:  Transesophageal Echo (TEE) Protocol .................................................... 112 
28 APPENDIX XII:  ECHOCARDIOGRAPHY TR GRADING ................................................. 117 
29 APPENDIX XIII: SIX MINUTE WALK TEST GUIDELINES – AMERICAN THORACIC 
SOCIETY .................................................................................................................................. 119 
30 APPENDIX XIV:  Monitoring Exposure to Ionizing Radiation ............................................ 127 
31 APPENDIX XV:  Exceptions from ISO 14155 compliance ................................................. 128 
32 APPENDIX XVI: CONTINUED ACCESS STUDY ............................................................. 130 
32.1 
Overview ..................................................................................................................... 130 

TRILUMINATE Pivotal CIP 
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Study Name: TRILUMINATE Pivotal 
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32.2 
Clinical Investigation Design ....................................................................................... 130 
32.3 
Endpoints .................................................................................................................... 131 
32.3.1 
Imaging Sub-Study Endpoints ............................................................................. 132 
32.4 
Subject Selection and Withdraw ................................................................................. 132 
32.4.1 
Total Expected Duration of the Clinical Investigation .......................................... 132 
32.4.2 
Expected Duration of Each Subject’s Participation ............................................. 132 
32.4.3 
Estimated Time Needed to Select Required Number of Subjects ....................... 132 
32.5 
Treatment and Evaluation of Endpoints ..................................................................... 132 
32.5.1 
Follow-Up Assessments ...................................................................................... 132 
32.6 
Schedule of Events ..................................................................................................... 134 
32.7 
Statistical Considerations ........................................................................................... 135 
32.7.1 
Analysis Population ............................................................................................. 135 
32.8 
Identical Sections ....................................................................................................... 135 
33 APPENDIX XVII: REVISION HISTORY ............................................................................. 136 
 
 
 
 
 
COMPLIANCE STATEMENT:   
This clinical investigation will be conducted in accordance with this Clinical Investigation Plan, the 
Declaration of Helsinki, applicable Good Clinical Practices and regulations (e.g., US 21 CFR Part 
50, 21 CFR Part 56, 21 CFR Part 812 and OUS ISO14155:2020) and the appropriate local 
legislation(s). The most stringent requirements, guidelines or regulations must always be 
followed. The conduct of the clinical investigation will be approved by the appropriate Institutional 
Review Board (IRB)/Ethics Committee (EC) of the respective investigational site and by the 
applicable regulatory authorities (e.g., FDA, PMDA, MHRA, etc.). 
 
 
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 12 of 136 
 
  
Protocol Summary 
Trial Name and Number 
Clinical TRIal to EvaLUate Cardiovascular OutcoMes IN 
PAtients Treated with the Tricuspid ValvE Repair System 
Pivotal (TRILUMINATE Pivotal)  
CIP No. ABT-CIP-10249 
Device Under 
Investigation 
TriClipTM  
 
Objective 
The objective of this trial is to evaluate the safety and 
effectiveness of the TriClipTM device in improving clinical 
outcomes in symptomatic patients with severe tricuspid 
regurgitation (TR) who have been determined by the site’s 
local heart team to be at intermediate or greater estimated 
risk for mortality or morbidity with tricuspid valve surgery. 
Design 
TRILUMINATE Pivotal is a prospective, multicenter, 
randomized, controlled, clinical trial of the TriClipTM device in 
symptomatic subjects with severe TR. 
 
Selected subjects will have to be determined by the site’s 
local heart team to be at intermediate or greater estimated 
risk for mortality or morbidity with tricuspid valve surgery.  
 
The trial will randomize approximately 450 eligible subjects at 
up to 80 sites, in a 1:1 ratio to receive either: 
 
• 
The TriClipTM Device (Device) Group:  Subjects will 
undergo TriClipTM implantation and will continue to be 
managed on medical therapy, per physician 
discretion, or 
• 
Medical Therapy (Control) Group:  Subjects will 
continue to be managed on medical therapy, per 
physician discretion. 
 
The primary endpoint will be assessed when the first 350 
randomized subjects complete 12-month follow-up, with 
additional powered secondary endpoints evaluated when all 
randomized subjects complete 24-month follow-up. Up to 3 
roll-in subjects per implanter will be permitted at sites without 
prior experience of TriClipTM device for treatment of the 
tricuspid valve. Subjects in the Control group will be allowed 
to cross-over to the Device group after the 12-month follow-
up is complete. 
 
An adaptive design with sample size re-estimation will be 
incorporated. 
 

TRILUMINATE Pivotal CIP 
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In addition, up to 200 subjects will be enrolled into a 
concurrent Single-arm cohort. This cohort will comprise 
subjects with tricuspid valve anatomies, where: 
• 
The likelihood of achieving TR reduction to moderate 
or less is low, and 
• 
The likelihood of achieving TR reduction of at least 1 
grade (as assessed using a 5-grade scale) is high 
Determination of enrollment into the Single-arm cohort will be 
made by an independent eligibility committee. 
 
An imaging sub-study (comprised of Cardiac magnetic 
resonance imaging, computed tomography and/or real-time 
echo) of approximately 100 subjects will be conducted to 
evaluate quantitative parameters associated with TR 
reduction.   
    
Key Inclusion Criteria 
• 
In the judgment of the sites local heart team, subject has 
been adequately treated per applicable standards 
(including medical management) and stable for at least 30 
days. The patient must be optimally treated, and 
confirmed with the EC: 
• 
Medical therapy for TR 
• 
Medical and/or device therapy, for mitral 
regurgitation, atrial fibrillation, coronary artery 
disease and heart failure 
• 
Subject is symptomatic with Severe TR despite being 
optimally treated, as described above.TR severity is 
determined by the assessment of a qualifying 
transthoracic echocardiogram (TTE) confirmed by the 
Echocardiography Core Lab (ECL).  The ECL will also 
request a transesophageal echocardiogram (TEE) to 
confirm TR etiology.  Note: If any cardiac procedure(s) 
occur after eligibility was determined and prior to TriClipTM 
procedure, TR severity 30-day after the cardiac 
procedure(s) will be reassessed 
• 
The cardiac surgeon of the site local heart team 
(consisting of one interventionalist, one cardiac surgeon, 
one heart failure specialist and one echocardiologist) 
concur that the patient is at intermediate or greater 
estimated risk for mortality or morbidity with tricuspid 
valve surgery. 
• 
New York Heart Association (NYHA) Functional Class II, 
III or ambulatory IV 
Key Exclusion Criteria 
• 
Systolic pulmonary artery pressure (sPAP) > 70 mmHg or 
fixed pre-capillary pulmonary hypertension as assessed 
by right heart catheterization (RHC) 
• 
Severe uncontrolled hypertension Systolic Blood Pressure 
(SBP) ≥ 180 mmHg and/or Diastolic Blood Pressure 
(DBP) ≥ 110 mm Hg) 

TRILUMINATE Pivotal CIP 
(Version F) 
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Study Name: TRILUMINATE Pivotal 
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 Page 14 of 136 
• 
Any prior tricuspid valve procedure that would interfere 
with placement of the TriClipTM device 
• 
Indication for left-sided (e.g. severe mitral regurgitation) or 
pulmonary valve correction in the prior 60 days  
• 
Pacemaker or ICD leads that would prevent appropriate 
placement of the TriClipTM  
• 
Tricuspid valve stenosis 
• 
Left Ventricular Ejection Fraction (LVEF) ≤20% 
• 
Tricuspid valve leaflet anatomy which may preclude clip 
implantation, proper clip positioning on the leaflets or 
sufficient reduction in TR.  This may include: 
• 
Evidence of calcification in the grasping area  
• 
Presence of a severe coaptation defect (> 2cm) of 
the tricuspid leaflets 
• 
Severe leaflet defect(s) preventing proper device 
placement 
• 
Ebstein Anomaly 
• 
Tricuspid valve anatomy not evaluable by TTE and TEE 
 
Primary Endpoints 
Randomized cohort 
The primary endpoint is a hierarchical composite of all-cause 
mortality or tricuspid valve surgery, heart failure 
hospitalizations, and quality of life improvement assessed 
using the Kansas City Cardiomyopathy Questionnaire 
(KCCQ) at 12 months.  The endpoint will be compared 
between the Device group and the Control group and 
evaluated in a hierarchical fashion as follows: 
• 
Time to all-cause death or tricuspid valve surgery 
• 
Number of Heart Failure (HF) Hospitalizations 
• 
Improvement of ≥15 points in KCCQ from baseline 
 
Single-arm Cohort 
The primary endpoint is survival at 12 months with a quality 
of life improvement (using KCCQ) of at least 10 points 
compared to baseline. 
 
Secondary Endpoints 
Randomized Cohort 
The following secondary endpoints will be assessed at the 
same time of the primary endpoints for labeling claims: 
• 
TR Reduction to moderate or less at 30-day post 
procedure. The endpoint will be assessed as the 
proportion of subjects who have moderate or less TR 
at 30 days. 
• 
Freedom from major adverse events (MAE) at 30 
days after procedure attempt (femoral vein puncture).  
Components of MAE consist of the following: 
o Cardiovascular Mortality, 

TRILUMINATE Pivotal CIP 
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 Page 15 of 136 
o New Onset Renal Failure, 
o Endocarditis Requiring Surgery, and 
o Non-Elective Cardiovascular Surgery for 
TriClipTM device-related AE post-index 
procedure. 
• 
Change in Kansas City Cardiomyopathy 
Questionnaire (KCCQ) at 12 months 
• 
Change in Six Minute Walk Test (6MWT) at 12 
months 
 
In addition, the following secondary endpoints will be 
assessed after all randomized subjects complete 24 months 
follow-up: 
• 
Recurrent HF hospitalizations at 24 months  
• 
Freedom from all-cause mortality, tricuspid valve 
surgery, and tricuspid valve intervention at 24 months  
 
Single-arm Cohort 
• 
TR Reduction by at least one grade at 30-day post 
procedure as compared to baseline. 
• 
Freedom from major adverse events (MAE) occurring 
after procedure attempt (femoral vein puncture) at 30 
days.  Components of MAE consist of the following: 
o Cardiovascular Mortality, 
o New Onset Renal Failure, 
o Endocarditis Requiring Surgery, and 
o Non-Elective Cardiovascular Surgery for 
TriClipTM device-related AE post-index 
procedure. 
• 
Change in 6MWT at 12 months, as compared to 
baseline 
• 
Recurrent HF hospitalizations at 12 months compared 
to the 12 months prior to enrollment 
• 
Freedom from all-cause mortality and tricuspid valve 
surgery at 12 months 
 
Descriptive Endpoints 
The following descriptive endpoints will be assessed and 
reported: 
• 
Technical Success 
• 
Device Success 
• 
Procedural Success 
• 
Incidence of peripheral edema requiring hospitalization at 
12 months, and annually through 24, 36, 48, and 60 
months 
• 
Incidence of ascites at 12 months, and annually through 
24, 36, 48, and 60 months 

TRILUMINATE Pivotal CIP 
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Study Name: TRILUMINATE Pivotal 
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• 
Incidence of IV diuretic administration (including 
outpatient clinics) at 12 months, and annually through 24, 
36, 48, and 60 months 
• 
Change in KCCQ score from baseline through 30 days, 6 
months, 12 months, and annually through 24, 36, 48, and 
60 months 
• 
SF-36 QoL scores at baseline, 30 days, 12 months and 
24 months (and change from baseline to follow-up) 
• 
Change in NYHA Functional Class (III/IV to I/II) from 
baseline through 30 days, 6 months, 12 months, and 
annually through 24, 36, 48, and 60 months 
• 
Change in 6MWT from baseline through 30 days, 6 
months, 12 months, and annually through 24, 36, 48, and 
60 months 
• 
Change in BNP/NT-proBNP from baseline through 30 
days, 6 months, 12 months, and annually through 24, 36, 
48, and 60 months 
• 
Change in gamma-GGT from baseline through 30 days, 6 
months, 12 months, and annually through 24, 36, 48, and 
60 months 
• 
Change in patient weight from baseline through 30 days, 
6 months,12 months, and annually through 24, 36, 48, 
and 60 months 
• 
Change in kidney function (assessed using eGFR) from 
baseline through 30 days, 6 months, 12 months, and 
annually through 24, 36, 48, and 60 months 
• 
Change in liver function (assessed using the MELD 
score) from baseline through 30 days, 6 months, 12 
months, and annually through 24, 36, 48, and 60 months 
• 
Change in right ventricular volumes assessed from 
baseline through 30 days, 6 months, 12 months post 
procedure, and annually through 24, 36, 48, and 60 
months 
• 
Echocardiographic endpoints assessed from baseline 
through 30 days, 6 months, 12 months, and annually 
through 24, 36, 48, and 60 months as follows: 
• 
TR severity grade 
• 
Tricuspid valve annulus diameter 
• 
Effective Regurgitant Orifice Area (EROA) 
• 
Regurgitant Volume 
• 
Vena Contracta (VC) Width 
• 
Right Ventricular End Diastolic Dimension 
(RVEDD) 
• 
Right Ventricular Fractional Area Change 
• 
Left Ventricular End Diastolic Volume (LVEDV) 
• 
Left Ventricular End Systolic Volume (LVESV) 
• 
Tricuspid Annular Plane Systolic Excursion 
(TAPSE) 

TRILUMINATE Pivotal CIP 
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Study Name: TRILUMINATE Pivotal 
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a quality record which will be retained per the local retention policy.  
 
 Page 17 of 136 
 
 
 
 
• 
Cardiac Output 
• 
Forward Stroke Volume (Left Ventricle) 
• 
Inferior Vena Cava Dimension 
• 
Same endpoints as assessed with 
echocardiography to be obtained from MRI/CT in 
the subset of patients participating in the imaging 
sub-study at baseline, 30 days and 12 months 
 
Sample Size / Targeted 
Number of Subjects to 
Receive Study Device 
Approximately 450 subjects will be randomized in a 1:1 ratio 
at up to 80 sites, out of which approximately 225 are 
expected to receive the TriClipTM device. Up to 200 additional 
subjects will be enrolled into a concurrent Single-arm cohort, 
all of whom will receive the TriClipTM device.  
 
Up to 3 roll-in subjects per implanter may be enrolled at sites 
with operators who do not have prior or recent experience 
using the TriClipTM device. 
 
Subject Follow-up 
Upon randomization, subjects will be scheduled for a 
“Treatment” visit.  At the “Treatment” visit, Device group 
subjects will undergo the TriClipTM procedure and Control 
group subjects will be seen by a Heart Failure specialist for a 
physical exam, including vital signs, cardiac health status and 
evaluation of heart failure medications. The Treatment visit 
must be completed within 14 days of randomization.  
 
Subjects will have required follow-up evaluations at these 
time points post- “Treatment” visit: Discharge (not applicable 
to control subjects), 30 days, 6 months, 12 months, 18 
months and annually thereafter through 5 years. 
 

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Study Name: TRILUMINATE Pivotal 
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 Page 18 of 136 
1 
INTRODUCTION 
There is growing evidence that untreated, severe, tricuspid regurgitation (TR) is an independent 
predictor of mortality. Current standard of care for the treatment of TR is medical therapy. 
Patients who are severely symptomatic have the option to undergo tricuspid valve surgery, 
which is associated with a high rate of morbidity and mortality (1) (2). Transcatheter repair of the 
tricuspid valve has gained considerable interest recently due to the minimally invasive nature of 
the procedures. The TriClipTM device is a less invasive percutaneous device designed to mimic 
surgical repair techniques by approximating the leaflets of the tricuspid valve. It is based on the 
same concept as the MitraClip® system, a percutaneous edge-to-edge repair technique for the 
treatment of mitral regurgitation, which received CE Mark in 2008, and FDA approval in 2013. 
The safety and efficacy of the MitraClip® has been well documented in over 1000 scientific 
publications. More than 80,000 patients have been treated with the MitraClip® system since CE 
Mark and FDA approval. The TriClipTM operates in a similar fashion to the MitraClip® system, 
with a modified delivery system to facilitate access and treatment of the tricuspid valve. 
The primary objective of this trial is to demonstrate the safety and effectiveness of the TriClipTM 
device in improving clinical outcomes in symptomatic patients with severe TR, who are at 
intermediate or greater estimated risk for mortality or morbidity with tricuspid valve surgery. This 
randomized controlled trial will compare the device under investigation (TriClipTM device) to 
Control (Medical Therapy). 
This clinical trial will be conducted in accordance with this Clinical Investigational Plan (CIP).  All 
investigators involved in the conduct of the clinical investigation will be qualified by education, 
training, or experience to perform their tasks and this training will be documented appropriately. 
 
2 
BACKGROUND AND RATIONALE  
2.1 Background 
2.1.1 Tricuspid Regurgitation Description and Etiology 
TR, or tricuspid valve insufficiency, is a failure of the tricuspid valve to close completely during 
systole resulting in leakage or “regurgitation” of blood from the right ventricle (RV) to the right 
atrium with each contraction of the RV.  Symptoms associated with TR, include ascites, 
peripheral edema, hepatomegaly, decreased appetite, jugular vein enlargement and/or 
abdominal fullness (1).  Additionally, TR severity is associated with decreased survival 
regardless of LVEF or pulmonary artery pressure (2). 
Normal tricuspid valve closure is facilitated by the presence of anterior, posterior and septal 
leaflets at the interface of the right atrium and right ventricle.  The 3 leaflets arise from the 
tricuspid annulus and are tethered to the RV via chordae tendinae and papillary muscles. Valve 
function is dependent on the proper form and function of all components of the valve complex. 
Similar to the etiologies of mitral regurgitation, TR results from either degenerative disease of 
the leaflets (known as primary or degenerative TR) or from pathologic annular dilation which 
may be in conjunction with RV dilation (known as secondary or functional TR).  Both result in 
mal-coaptation of the leaflets, which allows blood to flow backwards into the atrium.  The 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 19 of 136 
presence of either a pacemaker or an implantable cardioverter-defibrillator (ICD) lead that 
prevents proper coaptation of the leaflets can result in what is known as lead-induced TR (3). 
Persistent TR results in a volume-overloaded RV, which eventually leads to right heart failure.  
Functional TR due to RV enlargement is the most common etiology (4).  It is often associated 
with pulmonary hypertension (primary or secondary), RV dysfunction and/or atrial fibrillation.  Of 
the three leaflets, the anterior leaflet is the one that is most affected by annular dilation.  The 
septal leaflet is attached to the septum whose dilation is minimal, and dilation of the posterior 
leaflet is limited by the adjacent diaphragm.  As the tricuspid annulus dilates, the anterior and 
posterior leaflets are pulled apart from the septal leaflet (Figure 1) creating gaps resulting in 
regurgitant jets from the right ventricle.  
Figure 1: Tricuspid valve annular dilation 
 
Image modified from Tornos et. al (7) 
It was initially thought that treatment of mitral regurgitation (usually concomitant to TR), would 
also result in a reduction of TR (5). This perception has resulted in the tricuspid valve receiving 
little or no attention by the clinical community, thus being referred to as the “forgotten valve”.  
However, more recent analyses have shown that despite correction of left-sided valve disease, 
TR continues to worsen in some patients (6).  Symptoms of TR are not evident until the 
regurgitation is significant.  By the time of detection, patients are generally sicker with multiple 
co-morbidities putting them at high risk for cardiovascular surgery. Outcomes in patients with 
severe TR are significantly worse than those without TR, as demonstrated by multiple studies 
(2; 7; 8; 9).  
Current treatment guidelines for TR indicate medical therapy to address venous congestion 
(e.g., diuretics) and/or treatment of the underlying disease to reduce TR (e.g., surgery) (10; 1). 
Outcomes with isolated tricuspid valve surgery are suboptimal and have an associated 8% in-
hospital mortality which increases to 37% for patients who undergo repeat surgery (11).  
Similarly, Bernal et al., reported high in-hospital mortality (35%) for a similar population of 
patients undergoing reoperation (12). Consequently, isolated tricuspid valve surgeries are rarely 
performed.  Although recent studies have indicated that outcomes with tricuspid valve surgery 
have improved, current recommendations for isolated tricuspid valve surgery are limited to a 
Class II indication (1).  

TRILUMINATE Pivotal CIP 
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Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
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 Page 20 of 136 
Tricuspid valve surgery is a Class I indication for severe TR patients at the time of left-sided 
valve surgery, per ACC/AHA valvular guidelines (10).  Although 2017 ACC/AHA indication for 
TR intervention has not changed significantly (10), the 2017 ESC/EACTS guidelines for surgery 
encourages earlier surgical intervention (13). Surgical treatment for moderate or less TR 
continues to be a Class II indication. Therefore, the tricuspid valve is often untreated during the 
time of left-sided valve surgery, especially in patients with moderate or less TR severity.  Left 
untreated, TR severity is known to continue to progress in approximately 30% of these patients; 
thus, increasing the patient’s potential for morbidity/mortality risk with repeat operation to 
address the tricuspid valve (14). 
2.1.2 MitraClip® Experience in Treatment of Mitral Regurgitation 
Extensive clinical evidence has shown the safety and efficacy of the MitraClip® System in 
various worldwide trials involving over 4,000 patients to date. This collective data supports 
clinical safety of this device, effectiveness in mitral regurgitation (MR) reduction and 
improvements in echocardiographic measures of left ventricular (LV) function, and obvious 
improvement in patient Quality of Life (QoL). The MitraClip® received CE Mark in 2008 and 
FDA Approval in 2013 for percutaneous treatment of MR. The success of MitraClip® has driven 
physician interest in using a similar approach for reducing TR. 
The first human procedure using the predicate MitraClip® System was performed on June 27, 
2003 in Caracas, Venezuela. Only one procedure was performed in Venezuela. 
Since then, in the United States, the MitraClip® System has been studied under an 
Investigational Device Exemption (IDE G030064). The initial IDE consisted of three cohorts: 
EVEREST I (feasibility study), EVEREST II (safety and effectiveness study) and REALISM 
(continued access study). More recently a new IDE was initialed, (IDE G120024) to confirm 
safety and performance of the MitraClip® System in patients with functional mitral regurgitation. 
EVEREST II was a prospective, multi-center, randomized controlled trial where patients with 
moderate-to-severe (3+) or severe (4+) MR were randomized in a 2:1 ratio between the Device 
group (MitraClip® device) and the Control group (mitral valve surgery). The trial enrolled 279 
patients, 184 in the Device group and 95 in the Control group and were followed for 5 years. At 
5 years, the rate of the composite endpoint of freedom from death, surgery, or 3+ or 4+ MR in 
the as-treated population was 44.2% versus 64.3% in the percutaneous repair and surgical 
groups, respectively (p = 0.01). The difference was driven by increased rates of 3+ to 4+ MR 
(12.3% vs. 1.8%; p = 0.02) and surgery (27.9% vs. 8.9%; p = 0.003) with percutaneous repair. 
After percutaneous repair, 78% of surgeries occurred within the first 6 months. Beyond 6 
months, rates of surgery and moderate-to-severe MR were comparable between groups. Five-
year mortality rates were 20.8% and 26.8% (p = 0.4) for percutaneous repair and surgery, 
respectively. In multivariable analysis, treatment strategy was not associated with survival. 
The most recent study, COAPT, began enrollment on December 27, 2012 and completed on 
June 23, 2017, with a total of 614 patients at 78 centers in the United States and Canada. 
COAPT is a prospective, multicenter, randomized, parallel-controlled trial to evaluate the 
preliminary safety and effectiveness of the percutaneous MitraClip® System in patients with 
heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained 
symptomatic despite the use of maximal doses of guideline-directed medical therapy. The 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
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a quality record which will be retained per the local retention policy.  
 
 Page 21 of 136 
primary safety end point was freedom from device-related complications at 12 months; the rate 
for this end point was compared with a prespecified objective performance goal of 88.0%. 
Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 
312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 
months was 35.8% per patient-year in the device group as compared with 67.9% per patient-
year in the control group (P<0.001). The rate of freedom from device-related complications at 12 
months was 96.6% (P <0.001 for comparison with the performance goal). Death from any cause 
within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% 
in the control group (P<0.001). 
Overall, the MitraClip® clinical trials have shown consistently excellent safety and efficacy 
profile. Reduction of MR severity has shown improvements in symptoms, improved QoL 
measurements, and functional improvements in patients who had significant MR. 
2.1.3 MitraClip® Experience in Tricuspid Regurgitation 
As of February 2019, there have been at least 20 published manuscripts representing 
approximately 200 patients who have been treated with the MitraClip® device on the tricuspid 
valve as off-label/Compassionate Use. In general, selected patients are described to have 
significant tricuspid regurgitation with symptomatic heart failure (NYHA III or IV).  Patients had at 
least 1 co-morbidity reported and were deemed to be high risk for surgical intervention by the 
site heart team.   
The reports indicate that most patients received at least 1 MitraClip® device resulting in 
reduction in TR of at least 1 grade in > 90% of the cases.   Some reports have also indicated 
that reduction in echocardiographic measurements of vena contracta area and width, EROA, 
annular diameter, and TR volume were achieved.  Low rates of adverse events and no device-
related complications were reported. Observations from key publications where cohorts of 
consecutively treated patients have been studied are briefly described below: 
• 
Nickenig et al. has reported on the largest cohort to date which included data from 64 
patients treated with the MitraClip® at 10 centers (15). All patients had symptomatic 
moderate to massive TR, were on optimal medical treatment, and were considered 
unsuitable for surgery.  The MitraClip® device was used either for isolated tricuspid 
valve regurgitation (n=42) or for concomitant mitral and tricuspid valve (n=22) 
regurgitation.  At baseline, 93% of patients were in NYHA III/IV, 82% had LVEF <50%, 
and 95% experienced dyspnea.  Ninety-seven percent (97%) of the patients had 1 or 
more clip deployed at the tricuspid valve.  Post-procedure, 91% of the patients had at 
least 1 grade reduction in TR.  No intraprocedural death, cardiac tamponade, emergency 
surgery, stroke, myocardial infarction or major vascular complications were reported. 
There were 3 (5%) in-hospital deaths. 
• 
Orban et al. presented data with minimum 6 months follow-up on patients (n=50) who 
had the tricuspid valve treated using the MitraClip® (16).  Of the 50 patients treated, 36 
received the device for concomitant mitral and tricuspid valve treatment (N=36), while 14 
patients received the device for isolated TR treatment. A clip was successfully deployed 
in 94% of the cases. Post procedure, a majority (90%) of patients showed at least a 1 
grade reduction in TR severity and 79% had 1 class improvement in NYHA at 6-month 
follow-up.  Six-month clinical results demonstrated a 44% increase in 6MWT distance 

TRILUMINATE Pivotal CIP 
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Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
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a quality record which will be retained per the local retention policy.  
 
 Page 22 of 136 
and a trend of an average 6-point improvement in MLHFQ (Minnesota Living with Heart 
Failure Questionnaire). Eight (n=8) patients died, 14 patients had HF hospitalization, 2 
patients underwent tricuspid valve surgery, and 2 patients underwent a second tricuspid 
valve MitraClip® procedure. 
• 
Besler et al. presented data on 117 patients, the largest cohort to date, with a median 
follow-up of 184 days (17).  Of the 117 patients treated, 74 received the device for 
concomitant mitral and tricuspid valve treatment, while 43 patients received the device 
for isolated TR treatment. Procedural success (TR reduction ≥1) was achieved in 81% of 
patients. Of the patients reports, 24 died and 21 were readmitted for heart failure. 
Procedural success independently predicted the time free of death and admission for 
heart failure irrespective of concomitant mitral regurgitation. 
• 
Braun et al. recently reported 1 year follow-up, the longest to date, on patients (n=24) 
who had the tricuspid valve treated with the MitraClip® (18). During one-year follow-up 
nine patients died (37.5%) with causes of death including end-stage heart failure in four 
patients, sepsis in two patients, STEMI in one patient and unknown causes in two 
patients. The rate of patients with TR ≤2 improved from 4% (1/24) at baseline to 87% of 
the surviving patients (13/15) at one-year follow-up (p<0.001). Two patients underwent a 
second edge-to-edge procedure due to recurrent severe TR. The percentage of patients 
in NYHA ≤II improved from 0% (0/24) at baseline to 67% of the surviving patients (10/15) 
at one-year follow-up (p<0.001). 
Overall, the data show either a reduction in TR severity or other echocardiographic parameter(s) 
(i.e. vena contracta width, vena contracta area, etc.), along with an improvement in clinical 
symptoms, and/or improvement in quality of life measurements. No concerns associated with 
device safety have yet been reported.  
2.1.4 TriClipTM Experience 
The TRILUMINATE trial, initiated to obtain CE mark approval, is a prospective, single-arm, 
multi-center study of the Abbott transcatheter TriClip™ using a clip-based edge-to-edge repair 
technique.  The objective of the trial is to evaluate the safety and effectiveness of the TriClip™ 
in patients with symptomatic moderate or greater TR who are deemed appropriate for 
percutaneous transcatheter intervention by the site heart team. 
In general, patients who were NYHA class II or greater, with no left-sided heart disease, and 
who were treated per applicable standards (including medical management) were included in 
the study. Patients were excluded from the study if they had systolic pulmonary artery pressure 
>60mmHg, a prior tricuspid valve procedure, or either pacemaker or ICD leads which would 
inhibit proper TriClip™ placement. First a cardiac surgeon at the site assessed surgical risk 
status. Then the ECL graded the severity of TR.  Finally, patients were presented to an 
Independent Eligibility Committee (EC) that included a cardiac surgeon, an interventionalist, and 
an echocardiographer who reviewed pertinent medical history to make the final determination 
regarding eligibility of prospective subjects, including eligibility of tricuspid valve anatomy. Once 
the EC confirmed that the subject was eligible for the TriClip™ procedure, the subject was 
scheduled for the TriClip™ procedure.   
As of the data cut-off date (November 29, 2018), at which time the first 85 subjects treated with 
the TriClipTM reached their 30 day follow-up, 14 subjects had been treated in the US and 73 

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 Page 23 of 136 
subjects had been treated outside of US (total 87 subjects) in the TRILUMINATE trial (CE mark 
trial). Out of the 87 subjects, 85 had completed their 30-day follow-up. Mean age of the study 
population was 77.8 ± 7.9 years, and a majority of the subjects were female (65.9%). All 
subjects had moderate or greater TR, with the majority (94.0%) having severe TR. A majority of 
the subjects had significant comorbidities including atrial fibrillation (91.8%), hypertension 
(85.9%), and renal disease (45.9%) being the most common. All subjects were symptomatic 
with NYHA ≥II, with a majority (74.7%) of the subjects being in NYHA III/IV. Subjects had 
diminished quality of life and functional capacity with a mean KCCQ score of 52.19 ± 21.85 
points and a mean 6-minute walk test (6MWT) distance of 277.47 ± 137.20 m. 
An average of 2.2 ± 0.8 clips were implanted per procedure with at least 1 clip implanted in all 
subjects. Implant success and acute device success rates were each 100%, and the acute 
procedural success rate was 91.6%. Of the 185 clips implanted in 85 subjects, 77.3% were in 
the anterior-septal leaflet position, 20.0% in the septal-posterior position and 2.7% in the 
anterior-posterior position. Mean total procedure, device, and fluoroscopy durations were 152.7 
± 57.8 min, 75.2 ± 43.1 min and 23.3 ± 17.8 min respectively. 
Primary effectiveness endpoint of TR reduction of least 1 grade at 30-days was successfully 
met. At 30 days, 86.6% of subjects had their TR reduced by at least 1 grade, with a one-sided 
97.5% lower confidence limit of 77.3%, which was significantly greater than the pre-specified 
performance goal of 35% (p < 0.0001). At 30 days, a significantly greater proportion (79.8%) of 
subjects showed improvement in NYHA functional class and were categorized as NYHA class I 
or II compared to 25.3% of subjects at baseline. Subjects experienced a significant 
improvement in their quality of life assessed using the Kansas City Cardiomyopathy 
Questionnaire, with scores improving from 52.19 ± 21.85 at baseline to 67.24 ± 22.24 at 30 
days, a mean improvement of 14.20 ± 16.74 points. Similarly, subjects improved their 6MWT 
distance from 277.47 ± 137.20 at baseline to 304.46 ± 109.74 at 30 days, a mean improvement 
of 47.5 ± 69.7m.  
The primary safety endpoint of MAE rate at 6 months was met successfully. Through 6 months 
follow-up, the MAE rate estimated by the Kaplan-Meier method was 6%, less than the pre-
specified performance goal of 39% (p<0.0001). Three (3) subjects experienced cardiovascular 
mortality, 1 subject experienced myocardial infarction, and 1 subject experienced new onset 
renal failure. No subjects experienced stroke or non-elective cardiovascular surgery for TriClip™ 
device related adverse events occurring after the index procedure. The data demonstrates that 
the TriClip™ can be used to repair the tricuspid valve and reduce TR with excellent procedural 
success and associated clinical outcomes. Subjects experienced a significant improvement in 
quality of life and functional capacity at 30 days post procedure. No safety concerns were 
identified, with only 5 subjects experiencing a major adverse event through 6-month follow-up.  
2.2 Rationale for Conducting this Clinical Investigation  
Optimal medical therapy for the treatment of TR has not been well defined. Medical treatment 
primarily revolves around the use of diuretics; however, a proportion of patients continue to 
progress and suffer from the symptoms of TR.  Current treatment options for TR are surgical 
repair or replacement.  Typically, these procedures are done in conjunction with left-sided 
cardiac surgical procedures (e.g. Aortic Valve and/or Mitral Valve). Isolated tricuspid valve 
surgery is typically not offered to patients, particularly those with prior cardiac surgeries 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
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 Page 26 of 136 
TriClip G4 
XTW Delivery 
Sys CE 
TCDS0302- 
XTW 
Serialized 
Abbott  
EU 
Market Released 
 
 
3.2.2 Intended Indication for Use  
The TriClipTM is intended for the treatment of patients with symptomatic, severe tricuspid valve 
regurgitation, whose symptoms and TR severity persist despite being treated optimally with 
medical therapy. Where applicable, refer to the approved IFU in the respective region/country 
for the intended use of the TriClipTM device. 
3.2.3 Description of the Device Under Investigation (TriClip) 
Detailed information of the device can be found in the IFU.  Briefly, the TriClipTM configuration 
consists of two parts: 1) a Clip Delivery System, which includes an implantable Clip (TriClipTM 
device), a Steerable Sleeve and a Delivery Catheter; and 2) a Steerable Guide Catheter which 
includes a dilator (Figure 2). 
The Clip Delivery System is used to advance and manipulate the implantable TriClipTM for 
proper positioning and placement on the tricuspid valve leaflets. The Clip Delivery System is 
designed to deploy the implant in a way that requires multiple steps to ensure safe delivery of 
the device. The Steerable Guide Catheter provides a conduit to access the tricuspid valve and 
with the addition of Steerable Sleeve to position the Clip relative to the valve. The Delivery 
Catheter is designed to deliver and deploy the Clip. The Steerable Guide and Clip Delivery 
System are steered and actuated by the use of control knobs, levers and fasteners (Figure 2). 
The implantable Clip is fabricated with metal alloys and polyester fabric that are commonly used 
in cardiovascular implants. The Clip can be repeatedly opened, closed and inverted by 
deliberate manipulations of the Delivery Catheter Handle. The Clip positions are designed to 
allow the Clip to grasp and approximate the leaflets of the tricuspid valve. The Clip is available 
in two sizes with differing grasping widths: the NT (17mm) and XT (22mm). 
In addition, the TriClipTM G4 system gives users the option to perform simultaneous and/or 
independent gripper actuation through the manipulation of new Delivery Handle controls (i.e. 
Controlled Gripper Actuation feature) and two redesigned Gripper lines.  The TriClipTM G4 
Implant is available in 4 sizes including 2 additional Implant sizes: NTW and XTW, which have 
Implant Arms that are approximately 50% wider than the NT and XT Implant sizes (Figure 3). 
 
 
 
 
  

TRILUMINATE Pivotal CIP 
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 Page 27 of 136 
Figure 2:  TriClipTM Configuration 
 
Figure 3: TriClipTM G4 Configuration 
 
 
 

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3.2.4 Summary of Preclinical Studies  
Two non-GLP studies were performed with the MitraClip® NT device to evaluate injury and 
healing in the healthy, porcine tricuspid valve and surrounding structures.  
An acute study was conducted to assess the ability to coapt two tricuspid leaflets and evaluate 
injury and trauma to the tricuspid valve and surrounding structures post deployment. One 
MitraClip® was implanted in one animal, successfully coapting two tricuspid leaflets. Upon gross 
examination of the tricuspid valve and surrounding tissues, significant injury was not observed.  
A four week chronic study was conducted to assess the healing profile in the porcine tricuspid 
valve and evaluate the long term hemodynamic response after implantation with the MitraClip® 
device in one animal. The animal was implanted with two MitraClip® devices in the tricuspid 
valve and survived to the four week time point without any adverse events. Prior to termination, 
right sided hemodynamics were assessed and it was determined that there were no relevant 
hemodynamic changes. Gross pathology and histological evaluation of the implanted tricuspid 
valve showed that both clips were appropriately encapsulated in fibrous tissue. Tissue bridging 
between the coapted leaflets was also observed grossly and histologically. Overall, healing was 
appropriate for the four week time point and was similar to the healing observed at four weeks in 
the chronic GLP porcine mitral valve safety study.   
A chronic GLP safety study was performed with a 30 day and 90 day follow-up 
endpoint.  Twelve animals (n=6 at 30 days; n=6 at 90 days) were assessed for 3 endpoints: 1) 
overall health, 2) device deployment and hemodynamics, and 3) tissue response to the 
clip.  There were no clinically relevant changes in the clinical pathology and no clinically relevant 
gross or histological changes in non-cardiac organs, myocardium, or tricuspid valve attributed to 
the test device at either time point. There was near complete tissue encapsulation of the clip at 
30 days and complete encapsulation and endothelialization at 90 days. There was no evidence 
of clip embolization or thrombosis and the inflammatory response was determined to be 
appropriate. The pre-determined safety endpoints of the acceptance criteria were met for all 12 
animals including no observed adverse clinically relevant gross or histological changes in the 
myocardium or tricuspid valves attributed to the test article.   
3.2.5 Device Handling  
The Sponsor requires clinical sites to store all investigational products according to the labeling 
and Instructions for Use in a secure area to prevent unauthorized access or use.  
 
 
4 
CLINICAL INVESTIGATION DESIGN  
TRILUMINATE Pivotal trial is a prospective, multicenter, randomized, controlled, clinical trial of 
the TriClipTM device in symptomatic subjects with severe TR, who have been determined by the 
site’s local heart team to be at intermediate or greater estimated risk for mortality or morbidity 
with tricuspid valve surgery. 
The trial consists of two cohorts: a Randomized cohort and a Single-arm Cohort. Determination 
as to whether a patient is placed in the randomized arm or Single-arm will be made by the 
independent eligibility committee. Patients will be placed in the Single-arm cohort if they meet 
the following criteria: 

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 Page 29 of 136 
• 
The likelihood of achieving TR reduction of at least 1 grade (as assessed using a 5-
grade scale, See Appendix XII) is high, and 
• 
The likelihood of achieving TR reduction to moderate or less (≤ 2) is low 
All other patients will be randomized. 
After the patient has been determined to meet all general inclusion/exclusion criteria, and prior 
to randomization, the patient’s echocardiographic and key clinical data will be submitted for 
review to confirm eligibility.  First, the site will be required to submit echocardiograms to the 
echocardiography core laboratory (ECL) for confirmation of TR severity. Initial assessment of 
clippability will be performed based on consultation between the site heart team, the ECL and 
Abbott proctors.   Finally, an independent eligibility committee (EC) will assess each potential 
subject and confirm that the potential subject has been optimally treated with medical therapy 
(drug and device), ensure the tricuspid valve is amenable to the TriClipTM device and confirm 
overall eligibility. See Figure  for study flow chart. Subsequently, the EC will determine whether 
the patient will be considered for the Randomized or Single-arm of the trial.  
Potential subjects who have concurrent severe mitral regurgitation will not be immediately 
eligible for the trial. These subjects must be treated for the MR first and re-assessed at a later 
stage for inclusion into the trial.  
Randomization will occur in approximately 450 eligible subjects in a 1:1 ratio to receive either 
the TriClipTM device or medical therapy (control group), at up to 80 sites as follows:    
• 
TriClipTM Device (Device) Group:  Eligible subjects will undergo the TriClipTM procedure 
and will continue to be managed on medical therapy, per physician discretion. 
• 
Medical Therapy (Control) Group:  Eligible subjects will not undergo the TriClipTM 
procedure but will continue to be managed on medical therapy, per physician discretion. 
The Single-arm cohort will enroll up to 200 eligible subjects and all subjects will receive the 
TriClipTM device.  
Additionally, up to 3 roll-in subjects will be permitted per implanter without prior experience of 
transcatheter treatment of the tricuspid valve.  The trial will be conducted in US, Canada and 
Europe, with a minimum of 50% of the subjects in each cohort enrolled in the US. 

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SF-36 and NYHA during the follow-up visits (30-day visit and afterwards) will be performed by 
blinded study personnel. 
The primary and secondary endpoints (See Section 5) will be evaluated when the first 350 
subjects have completed their 12-month visit. Additional secondary endpoints will be evaluated 
in the Randomized cohort when the 450 patients complete their 24-month follow-up. An 
independent Clinical Events Committee (CEC) will adjudicate events including cause of death, 
HF hospitalization and components of major adverse events.  The independent ECL will assess 
echocardiographic endpoints. 
The Sponsor has designed this clinical investigation to involve as little pain, discomfort, fear, 
and any other foreseeable risk as possible for subjects. Refer to the Risk Analysis section of this 
clinical investigation plan for details. 
4.1 Clinical Investigation Procedures and Follow-up Schedule  
Each subject will be followed until their 5-year visit. Clinical Investigation visits will occur at 
Baseline (after confirmation of eligibility), Treatment visit, Discharge (not applicable to control 
subjects), 30-days, 6 months, 12 months, 18 months, and annually through 60 months (5 
years).  
4.2 Measures Taken to Avoid and Minimize Bias  
Due to the nature of the treatment in the two randomized groups, the subject, some site 
personnel and some Sponsor personnel will be aware of treatment assignment.  The following 
steps will be taken to minimize bias in the conduct of the trial and analyses of clinical data. 
4.2.1 Subject Recruitment and Randomization 
Investigational sites will attempt to recruit consecutive subjects who meet trial eligibility criteria. 
• 
Candidates will be considered for the trial after they have been informed of trial 
requirements and have signed the informed consent form.  See Section 6.2 Subject 
Screening and Informed Consent for additional details on subject screening and 
informed consent process.  
• 
Transthoracic echocardiographic criteria for trial eligibility will be confirmed by an 
independent ECL 
• 
All baseline tests and assessments must be completed prior to randomization 
• 
Subjects will be randomized only after the sites’ clinical personnel have confirmed and 
documented that the subject has met all eligibility criteria, the ECL has confirmed the TR 
severity eligibility criterion, the EC has confirmed that the subject is on optimal therapy, 
the tricuspid valve is clippable and have assigned the subject to the appropriate 
treatment arm. Subjects assigned to the Single-arm will not be randomized. 
• 
Randomization will be stratified by site and performed using permuted blocks (random 
block sizes), and block sizes will not be disclosed to the sites.  
• 
A centralized randomization service will be used.   
4.2.2 Maintaining Similar Levels of Follow-up 
To maintain similar levels of contact between the investigational site and subjects, all subjects 
will have a “Treatment” visit.  During the “Treatment” visit for the Control group, subjects will be 

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seen by a HF specialist, and will undergo a physical exam, including vital signs, cardiac health 
status and evaluation of heart failure medications.  Subjects in the Device group will undergo 
the TriClipTM procedure during the “Treatment” visit.   
4.2.3 Administration of Assessments 
Site personnel assessing NYHA Functional Class, administering the 6MWT and QoL 
questionnaires during the follow up visits (30-day visit and afterwards) will be blinded to the 
subject’s treatment assignment and will not be involved in day-to-day activities of the 
TRILUMINATE Pivotal trial.  Additionally, personnel performing these assessments will not have 
access to the electronic case report forms (eCRFs).  A standardized script will be used when 
administering the assessments and the subject will be reminded to not reveal their treatment 
history to the administrator.  To minimize bias and undue influence, the QoL questionnaires will 
be completed by the subject, unless the subject is unable to complete the questionnaire on their 
own (in such cases, a note to file must be completed to document the inability of subject to 
complete the questionnaire).      
4.2.4 Eligibility Committee (EC) 
An independent EC will comprise, at a minimum, representatives from the following specialties: 
heart failure specialist, interventional cardiologist and echocardiologist. The EC will determine if 
the subject is being managed according to optimized medical therapy, evaluate the clippability 
of the tricuspid valve and determine whether the subject will be enrolled in the Randomized or 
Single-arm cohort.   Review will be performed via teleconference with presentation (i.e. Webex) 
or other formats on a regular basis (i.e. weekly) between the EC, ECL representative, and a 
study site(s) representative(s) of the proposed subject(s). The composition, guiding policies, and 
operating procedures governing the EC are described separately in the charter. 
4.2.5 Review of Echocardiography Images 
TR severity and other echocardiographic measurements will be assessed by an independent 
ECL at screening, baseline and follow-up.  Prior to enrollment, the ECL will confirm subject’s 
screening echocardiography images for TR severity per the guideline for TR grading (defined in 
Appendix XII).  Finally, the ECL will be responsible for assessing TR severity and 
echocardiographic analyses at all visits (baseline and follow-ups).  
4.2.6 Safety and Effectiveness Monitoring 
• 
All adverse events will be reviewed by Abbott Clinical Safety team. 
• 
Adverse events requiring adjudication will be submitted to an independent CEC.  See 
section 11.7.4. 
• 
A Data Monitoring Committee (DMC) will review accumulating safety and effectiveness 
data as described in Section 11.7.3.  
4.2.7 Follow-Up Compliance 
The Sponsor will work with investigational sites to maintain high follow-up compliance. The 
following are strategies for increasing compliance: 
• 
During the site initiation visit, the Sponsor will emphasize to the site the importance of 
subject follow-up, and that the site should communicate this importance to each subject. 

TRILUMINATE Pivotal CIP 
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Study Name: TRILUMINATE Pivotal 
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• 
Sites should promptly reschedule any missed subject visits, and to reinforce the 
necessity of a follow-up visit to subjects. 
• 
If a scheduled visit is missed due to subject illness, transportation issues, or travel, the 
site should: 
o Reinforce the necessity of follow-up visits; 
o Identify alternate transportation sources, and involve the Sponsor if necessary. 
• 
Sites will be instructed to ask subjects who withdraw during the trial to provide the 
reason for withdrawal and ask them if the investigator may contact them to check their  
vital status at the end of the trial follow-up.   
• 
Follow-up rates will be monitored closely so follow-up problems may be identified and 
addressed as soon as possible.   
• 
For subjects lost-to-follow-up, sites may be requested to examine the Social Security 
Death Index to determine subject status (only the status will be sent to Sponsor, not any 
subject identifying information). 
In addition to aforementioned steps, investigational sites will be educated on the importance of 
maintaining low rates of withdrawals in both Device and Control groups, and will be expected to 
make all efforts to maintain low withdrawals during trial conduct.  If necessary, an independent 
service (e.g. Hawthorne Effect) may be utilized to provide in-home visits to aid in follow-up 
compliance. Withdrawals from the trial may need discussion between investigator and the 
Sponsor. 
4.3 Continued Access Study Procedures and Follow-up Schedule  
Following the completion of enrollment in both the randomized and single-arm cohorts of the 
TRILUMINATE Pivotal trial, subjects from eligible sites will be enrolled into a continued access 
study. Details of the continued access study procedures and follow-up schedule are included in 
Appendix XVI.  
4.4 Suspension or Early Termination of the Clinical Investigation  
No formal statistical rule for early termination of the clinical investigation for insufficient 
effectiveness of the device under investigation is defined. 
The Sponsor reserves the right to discontinue the clinical investigation at any stage or reduce 
the follow-up period with suitable written notice to the investigator.  Possible reason(s) may 
include, but are not limited to: 
• 
Unanticipated adverse device effect (e.g., UADE) occurs and it presents an 
unreasonable risk to the participating subjects  
• 
Any oversight committee (e.g., Steering Committee, Data Monitoring Committee) makes 
a recommendation to stop or terminate the clinical investigation (such as higher 
frequency of anticipated adverse device effects)  
• 
Further product development is cancelled 
Should the clinical investigation be discontinued by the Sponsor, subjects will be followed per 
routine hospital practice with device-related AEs reported to the Sponsor as per 
vigilance/commercial reporting requirements.  

TRILUMINATE Pivotal CIP 
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Should early termination occur, the investigator shall return all clinical investigation materials 
(including devices) to the Sponsor, and provide a written statement as to why the premature 
termination has taken place to the IRB/EC (if applicable). All applicable clinical investigation 
documents shall be subject to the same retention policy as detailed in Section 12.5 of the CIP.   
A Principal Investigator, IRB/EC or regulatory authority may suspend or prematurely terminate 
participation in a clinical investigation at the investigational sites for which they are responsible. 
The investigators will follow the requirements specified in the Clinical Trial Agreement.   
If the Sponsor suspends or prematurely terminates the clinical investigation at an individual site 
in the interest of safety, the Sponsor will inform all other Principal Investigators.  
If suspension or premature termination occurs, the Sponsor will remain responsible for providing 
resources to fulfill the obligations from the CIP and existing agreements for following the 
subjects enrolled in the clinical investigation, and the Principal Investigator or authorized 
designee will promptly inform the enrolled subjects at his/her site, if appropriate. Additionally, an 
effort will be made to hasten the release of results if the study is terminated early. 
5 
 
ENDPOINTS  
5.1 
Randomized Cohort 
5.1.1 Primary Endpoint 
The primary endpoint is a hierarchical composite of all-cause mortality or tricuspid valve 
surgery, heart failure hospitalizations, and quality of life improvement assessed using the KCCQ 
at 12 months.  The endpoint will be evaluated in a hierarchical order as follows: 
• 
Time to all-cause death or tricuspid valve surgery 
• 
Number of Heart Failure (HF) Hospitalizations 
• 
An Improvement of ≥15 points in KCCQ from baseline 
HF Hospitalization includes any of the following:   
1) Hospitalization (≥ 24 hours) with the primary reason for admission as acute decompensated 
HF and administration of intravenous or mechanical heart failure therapies, especially IV 
administration of diuretic therapy.  
2) An unscheduled or unplanned admission to the emergency department, hospital outpatient 
observation unit, or hospital inpatient unit, and IV administration of diuretic therapy. Overnight 
stays for IV administration of diuretic therapy at nursing home facilities, physical rehab or 
extended care facilities, including hospice, will be included in the definition of hospitalization if 
related to heart failure. 
3) Subject arrives in emergency department with clinical presentation meeting the criteria of HF, 
but dies in the emergency department before hospital admission. 
Elective heart failure “tune-ups” that occur following the TriClipTM procedure and prolong 
hospitalization will not count as a heart failure hospitalization. 
Based on the current experience, it is expected that the Device group may experience a 
mortality benefit, improved freedom from heart failure symptoms, as well as a quality of life 
improvement when their TR is treated. 

TRILUMINATE Pivotal CIP 
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The primary endpoint will be evaluated once 350 subjects have completed 12-month follow-up. 
An adaptive design with sample size re-estimation will be performed prior to assessment of the 
primary endpoint. If the sample size needs to be increased to maintain adequate study power, 
then the primary endpoint will be evaluated once the 12-month follow-up is completed with the 
larger sample size. 
 
The primary endpoint must be met for the study to be successful.  
5.1.2 Powered Secondary Endpoints  
The following secondary endpoints will be assessed at the same time of the primary endpoint 
for labeling claims: 
• 
TR Reduction to moderate or less at 30-day post procedure. The endpoint will be 
assessed as the proportion of subjects who have moderate or less TR at 30 days. 
• 
Freedom from major adverse events (MAE) occurring after procedure attempt (femoral 
vein puncture) at 30 days.  Components of MAE consist of the following: 
o Cardiovascular Mortality, 
o New Onset Renal Failure, 
o Endocarditis Requiring Surgery, and 
o Non-Elective Cardiovascular Surgery for TriClipTM device-related AE post-index 
procedure. 
• 
Change in KCCQ at 12 months  
• 
Change in 6MWT at 12 months  
The following secondary endpoints will be assessed after all randomized subjects complete 24-
month follow-up for additional labeling claims: 
• 
Recurrent HF hospitalizations at 24 months  
• 
Freedom from all-cause mortality, tricuspid valve surgery, and tricuspid valve 
intervention at 24 months  
5.1.3 Descriptive Endpoints  
The following descriptive endpoints will be assessed and reported: 
• 
Technical Success at exit from procedure room:  Alive with successful access, delivery 
and retrieval of the device delivery system, and deployment and correct positioning of a 
Clip, and no need for additional unplanned or emergency surgery or re-intervention 
related to the device or access procedure 
• 
Device Success at 30-day post-procedure:  Alive with original intended Clip(s) in place, 
and no additional surgical or interventional procedures related to access or device since 
completion of the original procedure, and intended performance of the Clip(s) (i.e. ≥1 
grade improvement in TR severity, no embolization, single leaflet device attachment, 
absence of para-device complications) 
• 
Procedural Success at 30-day post-procedure:  Device success, and no device or 
procedure related SAE 
• 
Incidence of peripheral edema requiring hospitalization at 12 months, and annually 
through 24, 36, 48, and 60 months 

TRILUMINATE Pivotal CIP 
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Study Name: TRILUMINATE Pivotal 
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• 
Incidence of ascites at 12 months, and annually through 24, 36, 48, and 60 months 
• 
Incidence of IV diuretic administration (including outpatient clinics) at 12 months, and 
annually through 24, 36, 48, and 60 months 
• 
Change in KCCQ score from baseline through 30 days, 6 months, 12 months and 
annually through 24, 36, 48, and 60 months 
• 
SF-36 QoL scores at baseline, 30 days, 12 months and 24 months (and change from 
baseline to follow-up) 
• 
Change in NYHA Functional Class (III/IV to I/II) from baseline through 30 days, 6 
months, 12 months and annually through 24, 36, 48, and 60 months 
• 
Change in 6MWT from baseline through 30 days, 6 months, 12 months and annually 
through 24, 36, 48, and 60 months 
• 
Change in BNP/NT-proBNP from baseline through 30 days, 6 months, 12 months, and 
annually through 24, 36, 48, and 60 months 
• 
Change in gamma-GGT from baseline through 30 days, 6 months, 12 months, and 
annually through 24, 36, 48, and 60 months 
• 
Change in patient weight from baseline through 30 days, 6 months, 12 months and 
annually through 24, 36, 48, and 60 months 
• 
Change in kidney function (assessed using eGFR) from baseline through 30 days, 6 
months, 12 months and annually through 24, 36, 48, and 60 months 
• 
Change in liver function (assessed using the MELD score) from baseline through 30 
days, 6 months, 12 months and annually through 24, 36, 48, and 60 months 
• 
Echocardiographic endpoints assessed from baseline through 30 days, 6 months, 12 
months and annually through 24, 36, 48, and 60 months post procedure, as follows: 
• 
TR severity grade 
• 
Tricuspid valve annulus diameter 
• 
Effective Regurgitant Orifice Area (EROA) 
• 
Regurgitant Volume 
• 
Vena Contracta Width 
• 
Right Ventricular End Diastolic Dimension (RVEDD) 
• 
Right Ventricular Fractional Area Change 
• 
Left Ventricular End Diastolic Volume (LVEDV) 
• 
Left Ventricular End Systolic Volume (LVESV) 
• 
Tricuspid Annular Plane Systolic Excursion (TAPSE) 
• 
Cardiac Output 
• 
Forward Stroke Volume (Left Ventricle) 
• 
Inferior Vena Cava Dimension 
5.2 
Single-arm Cohort 
5.2.1 Primary Endpoint 
The primary endpoint of the Single-arm cohort is survival at 12 months with quality of life 
improvement (assessed using KCCQ) of at least 10 points compared to baseline. In this cohort 
of sick patients in which it is believed TR cannot be reduced to moderate or less, it is expected 
that there will still be significant improvement in quality of life at 12 months post treatment. 

TRILUMINATE Pivotal CIP 
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Study Name: TRILUMINATE Pivotal 
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 A group sequential design with one interim analysis will be performed. The primary endpoint 
will be evaluated once the first 100 subjects have completed 12-month follow-up. If the primary 
endpoint is successfully met at the interim analysis, the Single-arm cohort endpoints will be 
summarized descriptively for all additional subjects enrolled after the first 100. If unsuccessfully 
met, the primary endpoint will be re-analyzed when all enrolled subjects in the Single-arm cohort 
have completed 12 months follow-up. 
 
5.2.2 Secondary Endpoints  
The following secondary endpoints will be assessed at the same time of the primary endpoint: 
• 
TR Reduction by at least one grade at 30-day post procedure as compared to baseline. 
• 
Freedom from MAE occurring after procedure attempt (femoral vein puncture) at 30 
days.  Components of MAE consist of the following: 
o Cardiovascular Mortality, 
o New Onset Renal Failure, 
o Endocarditis Requiring Surgery, and 
o Non-Elective Cardiovascular Surgery for TriClipTM device-related AE post-index 
procedure. 
• 
Change in 6MWT at 12 months, as compared to baseline 
• 
Recurrent HF hospitalizations at 12 months compared to the rate of heart failure 
hospitalizations in the prior 12 months 
• 
Freedom from all-cause mortality and tricuspid valve surgery at 12 months 
5.2.3 Descriptive Endpoints  
The following descriptive endpoints will be assessed and reported for all subjects enrolled into 
the Single-arm cohort: 
• 
Technical Success at exit from procedure room:  Alive with successful access, delivery 
and retrieval of the device delivery system, and deployment and correct positioning of a 
Clip, and no need for additional unplanned or emergency surgery or re-intervention 
related to the device or access procedure 
• 
Device Success at 30-day post-procedure:  Alive with original intended Clip(s) in place, 
and no additional surgical or interventional procedures related to access or device since 
completion of the original procedure, and intended performance of the Clip(s) (i.e. ≥1 
grade improvement in TR severity, no embolization, single leaflet device attachment, 
absence of para-device complications) 
• 
Procedural Success at 30-day post-procedure:  Device success, and no device or 
procedure related SAE 
• 
Incidence of peripheral edema requiring hospitalization at 12 months, and annually 
through 24, 36, 48, and 60 months 
• 
Incidence of ascites at 12 months, and annually through 24, 36, 48, and 60 months 
• 
Incidence of IV diuretic administration (including outpatient clinics) at 12 months, and 
annually through 24, 36, 48, and 60 months 
• 
Change in KCCQ score from baseline through 30 days, 6 months, 12 months and 
annually through 24, 36, 48, and 60 months 

TRILUMINATE Pivotal CIP 
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Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
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• 
SF-36 QoL scores at baseline, 30 days, 12 months and 24 months (and change from 
baseline to follow-up) 
• 
Change in NYHA Functional Class (III/IV to I/II) from baseline through 30 days, 6 
months, 12 months and annually through 24, 36, 48, and 60 months 
• 
Change in 6MWT from baseline through 30 days, 6 months, 12 months and annually 
through 24, 36, 48, and 60 months 
• 
Change in BNP/NT-proBNP from baseline through 30 days, 6 months, 12 months, and 
annually through 24, 36, 48, and 60 months 
• 
Change in gamma-GGT from baseline through 30 days, 6 months, 12 months, and 
annually through 24, 36, 48, and 60 months 
• 
Change in patient weight from baseline through 30 days, 6 months, 12 months and 
annually through 24, 36, 48, and 60 months 
• 
Change in kidney function (assessed using eGFR) from baseline through 30 days, 6 
months, 12 months and 24, 36, 48, and 60 months 
• 
Change in liver function (assessed using the MELD score) from baseline through 30 
days, 6 months, 12 months and annually through 24, 36, 48, and 60 months 
• 
Echocardiographic endpoints assessed from baseline through 30 days, 6 months, 12 
months and annually through 24, 36, 48, and 60 months post procedure, as follows: 
• 
TR severity grade 
• 
Tricuspid valve annulus diameter 
• 
Effective Regurgitant Orifice Area (EROA) 
• 
Regurgitant Volume 
• 
Vena Contracta Width 
• 
Right Ventricular End Diastolic Dimension (RVEDD) 
• 
Right Ventricular Fractional Area Change 
• 
Left Ventricular End Diastolic Volume (LVEDV) 
• 
Left Ventricular End Systolic Volume (LVESV) 
• 
Tricuspid Annular Plane Systolic Excursion (TAPSE) 
• 
Cardiac Output 
• 
Forward Stroke Volume (Left Ventricle) 
• 
Inferior Vena Cava Dimension 
5.3 Imaging Sub-Study Endpoints  
A sub-study will be included to assess various measurements of TR severity and the effect of 
changes in TR on clinical endpoints. Cardiac magnetic resonance imaging (MRI) and/or cardiac-
gated computed tomography (CT) will be used as a basis for comparison to echocardiographic 
measurements. MRI and CT will be assessed at both baseline and 30 days, and CT will be 
assessed at 12 months on a total of at least 50 and up to 100 subjects at up to 15 qualified 
sites. Sites will be qualified based on their ability to perform the required MRI and CT 
acquisitions. Quantitative assessments of TR as well as right ventricular function will be 
compared between MRI, CT and TTE at baseline and at follow-up. TEE may be evaluated when 
available.  
Abbott will qualify relevant sites for MRI and CT acquisition through an experienced core 
laboratory. Any enrolled subject is eligible for participation in the sub-study provided they agree 

TRILUMINATE Pivotal CIP 
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Study Name: TRILUMINATE Pivotal 
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to undergo cardiac MRI/CT at the pre-specified time points described above.  Each MRI/CT 
acquisition must be performed within 72 hours of the TTE acquisition at the specified time 
points.  A separate cardiac MRI/CT acquisition protocol will be developed and provided to the 
participating sites in order to ensure uniform acquisition. 
5.4 Health Economic Data 
During the course of the trial, Abbott (or third-party designee) will collect health economic data.  
This includes gathering information regarding hospitalizations (index or otherwise). The data 
required may include billing information for items such as hospital care, physician services, 
laboratory tests and diagnostic procedures.  The Institution shall submit health economic data 
using eCRFs for the TriClip™ procedure and subsequent hospitalization events during the study 
follow-up period. 
 
6 
SUBJECT SELECTION AND WITHDRAWAL   
6.1 Subject Population  
This clinical investigation will enroll male and female subjects selected from the specified clinical 
investigation population. Subjects must provide written informed consent prior to conducting any 
investigation-specific procedures not considered standard of care.   
This investigation is designed to treat patients who present with symptomatic severe TR despite 
being optimized on medical therapy.  Additionally, the site heart team would have determined 
that the patient is at intermediate or greater estimated risk for mortality or morbidity with 
tricuspid valve surgery. The eligibility criteria for the trial are described below. 
   
   
6.2 Subject Screening and Informed Consent  
6.2.1 Subject Screening  
Potential patients presenting at the clinical sites will be fully informed about the clinical 
investigation, following the established Informed Consent process. Once Informed Consent is 
obtained, the clinical investigation-specific screening procedures may begin.   
Subjects must be screened for clinical investigation eligibility by member(s) of the site’s clinical 
investigation team (physician, research coordinator and/or site heart team) previously trained to 
the CIP, and if applicable, will be entered into a site-specific screening log.  
Patients meeting general inclusion criteria and no exclusion criteria will be asked to sign an 
Informed Consent form if they wish to participate in the clinical investigation.  
Screening of a subject for possible inclusion in the trial may commence once a subject has been 
identified as being symptomatic with severe TR despite optimal medical therapy. Subject’s 
general medical eligibility must be assessed by the site through subject interviews and medical 
record review prior to the TriClipTM procedure and within the time windows stipulated (see Table 
1 for more details).  Relevant standard of care tests performed prior to obtaining informed 
consent can be used to determine eligibility if those tests were within the screening time 
window.  Signed and dated informed consent must be obtained prior to any test/evaluation that 

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is not standard of care.  Additionally, signed and dated informed consent is required prior to 
any transmission of patient data to the ECL or Sponsor. 
Screening assessments within 90 days prior to Eligibility Committee Review: 
• 
Transthoracic and transesophageal echocardiographic (TTE and TEE) images to be 
obtained and submitted to the ECL. Site must review the TEE images and confirm that 
subject has TR and suitable tricuspid valve anatomy, without intracardiac mass, 
thrombus or vegetation.  Abbott personnel may provide support to sites in reviewing TEE 
images.  See Appendix X and XI for echo protocol. 
o If the TEE is not standard of care at the site, the subject must provide informed 
consent prior to the echocardiographic study. 
• 
Medical history must be obtained, including review of subject’s medical records. 
• 
Physical exam including vital signs (weight, heart rate and blood pressure)  
• 
Blood test performed. 
• 
Right heart catheterization to assess and rule out pulmonary hypertension as the cause 
of TR. 
• 
Subject is examined by the site investigator experienced in treating heart failure, to 
assess the subject for appropriateness and optimization of medical and device therapy. 
• 
Subject is evaluated by the site local heart team to confirm that they are adequately 
treated per applicable standards, including for coronary artery disease, left ventricular 
dysfunction, mitral regurgitation, TR and heart failure.  Subjects with current or prior 
symptoms of heart failure and reduced LVEF must be on stable GDMT recommended 
according to current guidelines as standard of care for heart failure therapy in the United 
States.  See ‘APPENDIX II: Definitions’ for definition of optimal therapy.  
• 
NYHA Functional Class assessment. 
• 
A 12-lead ECG must be performed. 
• 
Subject’s pertinent medical information will be assessed by the EC. After the ECL has 
confirmed subject eligibility, sites will be notified by Sponsor to compile and submit 
information to assess clippability to the EC.  
The following screening information must be captured on the appropriate electronic Case 
Report Forms (eCRFs): 
• 
Inclusion and Exclusion criteria 
• 
Demographics (e.g., age at time of consent, gender, race/ethnicity)  
• 
Informed Consent date 
In case the subject does not meet all inclusion criteria or meets any of the exclusion criteria, the 
subject is considered a screening failure. The Principal Investigator or the delegated clinical 
investigation personnel will record the screening failure in the hospital records and on a 
screening log as required.  
6.2.2 Informed Consent  
The Investigator or his/her authorized designee (if applicable) will conduct the Informed Consent 
process, as required by applicable regulations and the center’s IRB/EC. This process will 
include a verbal discussion with the subject on all aspects of the clinical investigation that are 

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relevant to the subject’s decision to participate, such as details of clinical investigation 
procedures, anticipated benefits, and potential risks of clinical investigation participation. 
Subjects must be informed about their right to withdraw from the clinical investigation at any 
time and for any reason without sanction, penalty or loss of benefits to which the subject is 
otherwise entitled. Withdrawal from the clinical investigation will not jeopardize their future 
medical care or relationship with the investigator.   
During the discussion, the Principal Investigator or his/her authorized designee will avoid any 
improper influence on the subject and will respect subject’s legal rights. Financial incentives will 
not be given to the subject. Subjects may be compensated for time and travel directly related to 
the participation in the clinical investigation. The subject shall be provided with the Informed 
Consent form written in a language that is understandable to the subject and has been 
approved by the center’s IRB/EC. The subject shall have adequate time to review, ask 
questions and consider participation. The Principal Investigator or his/her authorized designee 
will make efforts to ensure that the subject understands the information provided. If the subject 
agrees to participate, the Informed Consent form must be signed and dated by the subject and 
thereafter by the person obtaining the consent prior to any clinical investigation-specific 
procedures. The signed original will be filed in the subject’s hospital or research charts, and a 
copy will be provided to the subject.  
Failure to obtain informed consent from a subject prior to clinical investigation enrollment should 
be reported to Sponsor within 5 working days and to the reviewing center’s IRB/EC according to 
the IRB’s/ EC’s reporting requirements.  
If, during the clinical investigation, new information becomes available that can significantly 
affect a subject's future health and medical care, the Principal Investigator or his/her authorized 
designee (if applicable) will provide this information to the subject. If relevant, the subject will be 
asked to confirm their continuing informed consent in writing. 
6.2.2.1 Special Circumstances for Informed Consent 
Incapacitated individuals, defined as persons who are mentally ill, mentally handicapped, or 
individuals without legal authority, are excluded from the study population. 
Sites may enroll individuals unable to read or write in this clinical investigation. 
 
Sites will obtain informed consent through a supervised oral process. An independent witness will 
be present throughout the Informed Consent process. A member of the site’s clinical investigation 
team previously trained to the CIP will read the written Informed Consent form and any other 
information aloud and explain to the prospective subject or his/her legally acceptable 
representative and will sign and personally date the Informed Consent form. The witness will also 
sign and personally date the Informed Consent form attesting that the information was accurately 
explained, and that informed consent was freely given. In addition, no incentives or financial 
inducements will be provided to these patients or their legally authorized representatives for their 
participation in the clinical investigation. 
 
Individuals under the age of 18 or age of legal consent are excluded from the study population. 
Pregnant or breastfeeding women are excluded from the study population. 

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In addition, an authorization for use and disclosure of the subject’s protected health information, 
in accordance with the Health Insurance Portability and Accountability Act (HIPAA), must be 
obtained from the subject.   
 
6.3 Eligibility Criteria  
Assessment for general eligibility criteria is based on medical records of the site and interview 
with a candidate patient. If some of the clinical and laboratory tests are not included in site 
standard tests, they must be done but after written informed consent is obtained.  
  
6.3.1 Inclusion Criteria 
Subjects must meet all of the following inclusion criteria in order to participate in the trial: 
1. In the judgment of the site local heart team, subject has been adequately treated per 
applicable standards (including medical management) and stable for at least 30 days as 
follows: 
• 
Optimized medical therapy for treatment of TR (e.g. diuretics) 
• 
Medical and/or device therapy, for mitral regurgitation, atrial fibrillation, coronary 
artery disease and heart failure 
The EC will confirm that the subject has been adequately treated medically.  
2. Subject is symptomatic with Severe TR despite being optimally treated as described in 
(1). TR severity is determined by the assessment of a qualifying TTE and confirmed by 
the ECL.  The ECL will also request a TEE to confirm TR etiology.  Note: If any cardiac 
procedure(s) occur after eligibility was determined, TR severity will need to be re-
assessed 30 days after the cardiac procedure(s).  
3. The cardiac surgeon of the site local heart team concur that the patient is at intermediate 
or greater estimated risk for mortality or morbidity with tricuspid valve surgery.  
4. New York Heart Association (NYHA) Functional Class II, III or ambulatory class IV 
5. In the judgment of the TriClipTM implanting Investigator, femoral vein access is 
determined to be feasible and can accommodate a 25 Fr catheter.  
6. Age ≥18 years at time of consent. 
7. Subject must provide written informed consent prior to any trial related procedure. 
6.3.2 Exclusion Criteria  
Subjects who meet any of the following exclusion criteria may not participate in the trial: 
1. Systolic pulmonary artery pressure (sPAP) > 70 mmHg or fixed pre-capillary pulmonary 
hypertension as assessed by right heart catheterization (RHC).  
2. Severe uncontrolled hypertension Systolic Blood Pressure (SBP) ≥ 180 mmHg and/or 
Diastolic Blood Pressure (DBP) ≥ 110 mm Hg) 
3. Any prior tricuspid valve procedure that would interfere with placement of the TriClipTM 
device 
4. Indication for left-sided (e.g. severe aortic stenosis, severe mitral regurgitation) or 
pulmonary valve correction prior 60 days.  Note: Patients with concomitant Mitral and 
tricuspid valve disease will have the option of getting their MR treated, and wait 60 days 
prior to being reassessed for the trial.  

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5. Pacemaker or ICD leads that would prevent appropriate placement of the TriClipTM Clip.   
6. Tricuspid valve stenosis - Defined as a tricuspid valve orifice of ≤ 1.0 cm2 and/or mean 
gradient ≥5 mmHg as measured by the ECL 
7. Left Ventricular Ejection Fraction (LVEF) ≤20% 
8. Tricuspid valve leaflet anatomy which may preclude clip implantation, proper clip 
positioning on the leaflets or sufficient reduction in TR.  This may include: 
a. Evidence of calcification in the grasping area  
b. Presence of a severe coaptation defect (> 2cm) of the tricuspid leaflets.  
c. Severe leaflet defect(s) preventing proper device placement  
d. Ebstein Anomaly - Identified by having a normal annulus position while the valve 
leaflets are attached to the walls and septum of the right ventricle. 
9. Tricuspid valve anatomy not evaluable by TTE and TEE 
10. Active endocarditis or active rheumatic heart disease or leaflets degenerated from 
rheumatic disease (i.e. noncompliant, perforated). 
11. MI or known unstable angina within prior 30 days  
12. Percutaneous coronary intervention within prior 30 days  
13. Hemodynamic instability defined as systolic pressure < 90 mmHg with or without 
afterload reduction, cardiogenic shock or the need for inotropic support or intra-aortic 
balloon pump or other hemodynamic support device. 
14. Cerebrovascular Accident (CVA) within prior 90 days 
15. Chronic dialysis 
16. Bleeding disorders or hypercoagulable state 
17. Active peptic ulcer or active gastrointestinal (GI) bleeding 
18. Contraindication, allergy or hypersensitivity to dual antiplatelet and anticoagulant therapy 
Note: Contraindication to either antiplatelet or anticoagulant therapy (individually not 
both therapies) is not an exclusion criterion. 
19. Ongoing infection requiring current antibiotic therapy (if temporary illness, patients may 
enroll 30 days after discontinuation of antibiotics with no active infection). 
20. Known allergy or hypersensitivity to device materials 
21. Evidence of intracardiac, inferior vena cava (IVC), or femoral venous mass, thrombus or 
vegetation. 
22. Life expectancy of less than 12 months 
23. Subject is currently participating in another clinical trial that has not yet completed its 
primary endpoint. 
24. Subject is currently participating in another clinical investigation for valvular heart 
disease(s). 
25. Pregnant or nursing subjects and those who plan pregnancy during the clinical 
investigation follow-up period.  Female subjects of child-bearing potential are required to 
have a negative pregnancy test done within 7 days of the baseline visit per site standard 
test. Female patients of childbearing potential should be instructed to use safe 
contraception (e.g., intrauterine devices, hormonal contraceptives: contraceptive pills, 
implants, transdermal patches hormonal vaginal devices, injections with prolonged 
release.) It is accepted, in certain cases, to include subjects having a sterilized regular 
partner or subjects using a double barrier contraceptive method. 
26. Presence of other anatomic or comorbid conditions, or other medical, social, or 
psychological conditions that, in the investigator’s opinion, could limit the subject’s ability 
to participate in the clinical investigation or to comply with follow-up requirements, or 
impact the scientific soundness of the clinical investigation results.  
   

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6.4 Subject Enrollment  
A patient is considered enrolled in the clinical investigation from the moment the patient 
provides written informed consent and has been confirmed to meet all inclusion criteria and 
none of the exclusion criteria. .  
 
Subjects will be assigned a subject ID upon informed consent and entry into the database. Such 
subjects are registered in the trial.   
  
6.4.1 Enrollment of Medicare Beneficiaries 
This clinical trial will enroll appropriate Medicare beneficiaries that qualify based on the inclusion 
and exclusion criteria set forth in the trial. This IDE clinical trial adheres to all standards of 
Medicare coverage requirements set forth by the IDE and clinical trial coverage policies of the 
Center for Medicare and Medicaid Services (CMS). Section 16, Risks Analysis section, 
describes how all enrolled subjects, including Medicare beneficiaries, may be affected by the 
device under investigation. 
Subjects enrolled in the clinical investigation are expected to be consistent with the Medicare 
population based on age range, demographic characteristics and cardiovascular risk factors 
representative of the Medicare patient population, so as such, the clinical investigation results 
are expected to be generalizable to the Medicare population. 
 
6.4.2  Historically Under-Represented Demographic Subgroups  
The Sponsor intends to implement FDA's guidance on sex-specific data in medical device 
clinical investigations to ensure adequate representation of women and other traditionally under-
represented demographic subgroups in this clinical investigation.  To date, experience with 
transcatheter technologies for the tricuspid valve have shown the treatment population to be a 
majority female. As noted in the guidance, some barriers to participation of women and ethnic 
minorities in clinical investigations have traditionally been:  
• 
Lack of understanding about main obstacles to participation of such subgroups in clinical 
research   
• 
Inclusion/exclusion criteria potentially not needed to define the clinical investigation 
population may unintentionally exclude specific subgroups   
• 
Under diagnosis of disease etiologies and pathophysiology leading to under referral of 
demographic subgroups   
• 
Avoidance of specific subgroups by investigators and Sponsors due to the perception 
that it takes more time and resources to recruit them   
• 
Fear of fetal consequences (for female participants)   
• 
Family responsibilities limiting women's ability to commit time for follow-up requirements 
The Sponsor will take the following steps to ensure adequate representation of women and 
racial or ethnic minorities in this clinical investigation:   
• 
The Sponsor will provide training to investigational site personnel to ensure adequate 
representation of these demographic subgroups   

TRILUMINATE Pivotal CIP 
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• 
The Sponsor will regularly review enrollment data to investigate whether there is 
underrepresentation of these demographic subgroups   
• 
The Sponsor will regularly review withdrawal rates for under-represented subgroups and 
compare these rates with that in the overall clinical investigation population  
• 
As appropriate and necessary, the Sponsor will retrain sites on the importance of 
recruiting and retaining subjects in the clinical investigation  
• 
The Sponsor will approach sites without bias or consideration for specific demographic 
subgroups   
• 
The Sponsor will have informed consent materials in alternative languages and will work 
with sites and IRBs/ECs on recruitment materials   
6.5 Subject Withdrawal  
Each enrolled subject shall remain in the clinical investigation until completion of the required 
follow-up period; however, a subject’s participation in any clinical investigation is voluntary and 
the subject has the right to withdraw at any time without penalty or loss of benefit. Conceivable 
reasons for discontinuation may include, but not be limited to, the following:  
• 
Subject death  
• 
Subject voluntary withdrawal   
• 
Subject lost-to follow-up as described below   
The Sponsor must be notified of the reason(s) for subject discontinuation. The site will provide 
this information to the Sponsor. Investigators must also report this to their respective IRB/EC as 
defined by their institution’s procedure(s).   
No additional follow-up will be required or data recorded from subjects once withdrawn from the 
clinical investigation, except for the status (deceased/alive). 
  
However, if a subject withdraws from the investigation due to problems related to the safety or 
performance of the device under investigation, the investigator shall ask for the subject's 
permission to follow his/her status/condition outside of the clinical investigation.    
In case of subject withdrawal, the site should make attempts to schedule the subject for a final 
clinical investigation visit. At this final follow-up visit, the subject will undergo the following 
assessments:   
• 
12-lead ECG 
• 
Blood draw (Same as required for follow-up visits) 
• 
Physical exam including vital signs (weight, heart rate and blood pressure) 
• 
Echocardiogram – TTE 
• 
Modified Rankin Scale (Assessment of mRS should be done only after onset of 
stroke; not required after 12 months)  
• 
6-Minute Walk Test (6MWT) – See APPENDIX XIII for 6 Minute Walk Test 
Guidelines 
• 
Concomitant cardiovascular medications assessment 
• 
NYHA Functional Class assessment 
• 
KCCQ QoL questionnaire to be completed by the subject – must be administered by 
“blinded” study personnel.  Note: To minimize bias and undue influence, the QoL 
questionnaires will be completed by the subject, unless the subject is unable to 

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complete the questionnaire on their own (a note to file must be completed to 
document the inability of subject to complete the questionnaire) 
• 
Assess and record adverse events 
• 
Assess and record protocol deviations 
 
Lost-to-Follow-up  
If the subject misses two consecutive scheduled follow-up time points and the attempts at 
contacting the subject detailed below are unsuccessful, then the subject is considered lost-to-
follow-up. Site personnel shall make all reasonable efforts to locate and communicate with the 
subject (and document these efforts in the source documents), including the following, at each 
contact time point:  
• 
A minimum of three telephone calls over a period of 10 days to contact the subject or 
his/her relative/caregiver (where allowed per local regulations) should be recorded in the 
source documentation, including date, time and initials of site personnel trying to make 
contact.  
• 
If these attempts are unsuccessful, a letter (certified if applicable) should be sent to the 
subject.  The registered letter will request the subject to contact the site.  
• 
If the above attempts are unsuccessful, the patient’s general practitioner shall be 
contacted to investigate about the subject’s whereabouts and his/her health status 
(where allowed per local regulations). 
If a subject misses one or more non-consecutive follow-up contact time points, it will be 
considered a missed visit. The subject may then return for subsequent visits. If the subject 
misses two consecutive time points and the above-mentioned attempts at communicating with 
the subject are unsuccessful, the subject will be considered lost-to-follow-up.   
Note: Telephone contact with General Practitioner, non-clinical investigation cardiologist or 
relative without the presence of the subject or indirect documentation obtained via discharge 
letters will not be considered as subject contact. 
6.6 Total Expected Duration of the Clinical Investigation  
The clinical investigation duration is expected to be approximately 11 years, including 6 years 
for enrollment and 5 years of follow-up.  
6.7 Expected Duration of Each Subject’s Participation  
Each subject will be expected to participate for a duration of five years from Treatment visit.  
6.8 Number of Subjects   
Approximately 450 subjects will be enrolled in the clinical investigation and randomized 1:1 to 
either the Device Group or to the Control Group. Enrollment into the Randomized cohort will 
continue until (1) the sample size re-estimation results are received and (2) enrollment meets 
the re-estimated sample size. The Single-arm cohort will enroll up to 200 eligible subjects, with 
enrollment continuing until the Randomized cohort has completed enrollment. Up to 3 roll-in 
subjects will be permitted per implanter without prior experience with the TriClipTM device.   

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No site may enroll more than 25% of the total subjects.  
  
6.9 Estimated Time Needed to Select Required Number of Subjects  
   
7 
TREATMENT AND EVALUATION OF ENDPOINTS  
7.1 Eligibility Committee Review 
The EC must confirm the following and determine in which cohort the patient will be placed: 
• 
Tricuspid valve leaflet anatomy is amenable to TriClipTM implantation 
• 
Subject is on optimal medical therapy for both drug and device regimen for any cardiac 
conditions, per applicable standards. 
o Optimized medical therapy for treatment of TR (e.g. diuretics) 
o Medical and/or device therapy, for mitral regurgitation, atrial fibrillation, coronary 
artery disease and heart failure 
Confirmation of the above eligibility review will be documented. 
7.2 Roll-in Subjects 
The decision to identify a subject as a roll-in will depend on the level of experience of the 
Implanter with the device.  Roll-in subjects will be designated by the Sponsor as such prior to 
treatment and will not undergo randomization.  An implanter may perform up to 3 roll-in 
procedures prior to beginning the randomization phase of the trial based on the following 
criteria: 
• 
Implanters that do not have prior experience with the TriClipTM device OR that have not 
performed a TriClipTM procedure in the prior 12 months may perform up to 3 roll-in 
procedures upon approval from the Sponsor 
The site must receive authorization from the Sponsor to enroll each roll-in case.  
7.3 Baseline  
7.3.1 Baseline Clinical Assessments  
Baseline visit must be performed within 14-days after eligibility has been confirmed by the EC. 
Baseline assessments may occur on the day of treatment but prior to randomization (for 
randomized subjects): 
• 
Baseline TTE imaging must be obtained.  If screening TTE imaging was performed 
within 14 days, then screening images may be used as baseline. 
• 
A physical exam including an assessment of subject’s cardiac status and vital signs 
measures must be completed. 
• 
Blood tests performed. 
• 
Concomitant cardiovascular medications must be documented. 
• 
A 12-lead ECG must be performed. 

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• 
Site must reassess subject eligibility and reconfirm that the subject meets eligibility 
criteria.  If there has been significant change in subject’s overall condition (i.e. due to 
recent MI, stroke, etc.), it may be necessary to update assessments completed during 
the screening process, such as TTE, etc. 
• 
If site is participating in the imaging sub-study, subject must undergo an MRI and CT. 
• 
A standardized script will be used when administering the following assessments: 
o KCCQ and SF-36 QoL questionnaires must be completed by the subject; Note: 
To minimize bias and undue influence, the QoL questionnaires will be completed 
by the subject, unless the subject is unable to complete the questionnaire on 
their own (in such cases a note to file must be completed to document the 
inability of subject to complete the questionnaire). 
o The 6-Minute Walk Test (6MWT) must be administered according to the ATS 
Statement: Guidelines for the Six-Minute Walk Test, Official Statement of the 
American Thoracic Society, approved March 2002 (See APPENDIX XIII: 6 
Minute Walk Test Guidelines). 
o An assessment of NYHA Functional Class must be completed.   
7.4 Randomization 
Randomization shall occur within 14-days after eligibility has been confirmed by the EC. 
Randomization may occur on the day of treatment, but only after baseline assessments have 
been completed. 
For a subject in the randomized arm, the subject will be randomized in a 1:1 ratio between the 
Device Group or the Control Group according to a computer-generated randomization scheme 
accessed via the electronic data capture (EDC) system used for data submission.  
Subjects will either be assigned the Device Group or the Control Group.  Subjects who are 
randomized to the Device Group must be scheduled for the index procedure within 14 days. 
7.5 Blinding  
See Section 4.2.3 for blinding regarding administration of assessments. 
7.6 Index Procedure (Roll-In, Device Group and Single-arm Cohort) 
The index procedure must be performed within 0 to 14 days after randomization (baseline visit 
for Single- cohort and Roll-in cohort).  If complications arise during the procedure, it may be 
necessary to convert to an open surgical procedure.  Emergency surgical back-up should be 
available as per the institution’s standard procedures. 
The Sponsor will be available to provide technical support to answer questions regarding the 
function and operation of the TriClipTM System.  Refer to the IFU for specific instruction on the 
use TriClipTM device, including handling requirements, preparation for use and precautions. 
7.6.1 Subject Preparation 
Subjects will be prepared for the procedure as per the institution’s standard practice for a 
percutaneous procedure and TEE. 

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Note:  Prior to performing the procedure, all Investigators must also undergo documented 
training by the Sponsor on the TriClipTM System and the CIP.  In addition, all Investigators must 
read and understand the IFU that accompanies the Device.   
Femoral vein catheterization will be completed in accordance with the IFU. 
7.6.2 Pre-Procedure 
7.6.2.1 Pre-Procedure Anticoagulation/Antiplatelet Therapy 
Perform pre-procedure anticoagulation/antiplatelet therapy according to institution standard of 
care for transcatheter cardiac procedures.  Otherwise, perform anticoagulation/antiplatelet 
therapy according to the recommended therapy in this section. 
Discontinue the use of warfarin for at least three (3) days prior to the scheduled TriClipTM 
procedure and it is suggested that the international normalized ratio (INR) is ≤1.7 prior to the 
TriClipTM procedure.  Similarly, discontinue dabigatran or factor Xa inhibitors medications for a 
sufficient duration to ensure restoration of normal coagulation, or per institution standard of 
care.  Subjects may be treated with heparin during this period at the treating physician’s 
discretion.  If heparin is used, it should be discontinued ≥8 hours prior to the TriClipTM procedure 
for subcutaneous low molecular weight heparin (LMWH) and ≥4 hours prior to the TriClipTM 
procedure for intravenous unfractionated heparin (UFH).  
7.6.2.2 Clopidogrel 
A loading dose of clopidogrel (≥300 mg) is recommended within 24 hours prior to the procedure 
(6-24 hours prior if possible) or immediately following the procedure.   
Note: A loading dose of clopidogrel may be considered even if the patient is taking clopidogrel 
on a daily basis either at home or in the hospital, as long as no other clopidogrel loading dose 
has been given within 24 hours.  However, clopidogrel use is optional and its use is left to the 
discretion of the investigator.   
Aspirin may also be used at operator discretion. If aspirin is to be used, a loading dose of 325 
mg acetylsalicylic acid (ASA) may be administered either pre- or immediately post- TriClipTM 
procedure. 
7.6.2.3 Antibiotic Therapy 
It is recommended to administer a single dose of intravenous broad spectrum antibiotics 
approximately one hour prior to initiation of the procedure. The type, dosage and timing of 
antibiotic is at the Investigator’s discretion or institution’s standard of care. 
7.6.2.4 Pre-procedure TEE Imaging  
Prior to the TriClipTM procedure, Device group and roll-in subjects must be assessed to ensure 
there is no significant change in subject’s overall condition (e.g., stroke, MI, active infection, 
endocarditis, hemodynamic instability, etc. post-randomization) that would preclude treatment.  
If the subject has experienced any significant change that would preclude treatment, the subject 
must be treated and rescheduled for the TriClipTM procedure as soon as possible.  Subjects are 
required to complete an additional transesophageal (TEE) echocardiogram study within 3 
days prior to the procedure to rule out the presence of intracardiac mass, thrombus or 
vegetation.  This echocardiogram may be performed immediately preceding initiation of the 

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TriClipTM procedure.  This echocardiogram will not be submitted to the ECL.  If an 
intracardiac mass, thrombus or vegetation or other change in echocardiographic eligibility is 
identified in the TEE performed immediately preceding the procedure, the procedure should be 
postponed until the change can be carefully evaluated by site and sponsor. If a thrombus is 
identified, the subject should be pharmacologically treated to resolve the thrombus and, if 
successful, the subject should be reassessed as soon as possible to undergo the TriClipTM 
procedure.  Such subjects will be considered enrolled even if they do not undergo the TriClipTM 
procedure. 
7.6.2.5 Pre-procedure ECG and Physical Exam  
A 12-lead ECG and physical exam must be performed within 24 hours prior to the procedure. 
7.6.2.6 Activated Clotting Time 
Prior to the TriClipTM procedure, baseline activated clotting time (ACT) will be determined 
following femoral vein puncture for the TriClipTM procedure.  ACT and heparin administration (or 
alternative anticoagulation therapy, e.g., bivalirudin) should be recorded. 
7.6.2.7 Procedural Anticoagulation Therapy 
Following femoral vein puncture, administer intravenous heparin (or alternative anticoagulation 
therapy, e.g., bivalirudin) in accordance with standard hospital practice.  Maintain an ACT 
(activated clotting time) of > 250 seconds throughout the procedure. Low molecular weight 
heparin and fondaparinux may not be used for procedural anticoagulation. 
7.6.3 TriClipTM Device Placement Procedure 
Please refer to IFU including storage and handling requirements, preparation for use, pre-use 
checks of safety and performance, and precautions to be taken after use.  All Investigators must 
read and understand the IFU that accompanies the Device. 
Femoral vein catheterization will be completed in accordance with the IFU. 
The Steerable Guide Catheter (Guide) is inserted into the femoral vein.  Fluoroscopic and 
echocardiographic (2D and/or 3D-TEE) guidance will be used during the procedure to visualize 
the device, vasculature and cardiac/valve anatomy.  See Appendix XIV: Monitoring Exposure 
to Ionizing Radiation for requirements for training and data gathering on ionizing radiation 
required per this protocol. For subjects with renal dysfunction, intravenous contrast should not 
be used during the procedure unless absolutely necessary.   
The Guide is positioned in the Inferior Vena Cava/Right Atrium (IVC/RA) and the TriClipTM 
Delivery System is inserted into the Guide and properly positioned over the tricuspid valve.  The 
TriClipTM Delivery Catheter is advanced until the TriClipTM emerges from the tip of the Guide into 
the right atrium.  Manipulations of the catheter tip (via the control knobs on the handles) will 
continue in the right atrium until the Clip is properly oriented perpendicular to the line of 
coaptation of the tricuspid valve leaflets.  The Clip is opened and advanced across the tricuspid 
valve into the ventricle then pulled back to grasp the leaflets.  2- and/or 3-dimensional 
echocardiography and color flow Doppler are used to evaluate leaflet insertion, Clip position and 
TR severity.  If the Clip is not positioned properly or TR has not been adequately reduced, 
additional grasping may be attempted and the Clip may be inverted and retracted into the right 
atrium as required for additional grasping attempts.  When placement is successful, the Clip is 

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closed and deployed from the Delivery Catheter.  The catheters are then removed from the 
subject. 
If placement of one Clip does not result in reduction in TR to a level deemed acceptable by the 
operator, then additional Clip(s) may be placed to further reduce TR. The Investigator should 
determine if there is adequate tricuspid valve orifice area to accommodate the additional Clip(s) 
without creating tricuspid stenosis. A maximum of four (4) Clips will be allowed to be implanted 
in subjects enrolled in this trial.  However, a fifth Clip may be used in the special circumstance if 
a previous Clip has detached from one leaflet or to stabilize excessive mobility of a previous 
Clip. 
Procedural echocardiograms (TTE and TEE) may be collected immediately post-procedure by 
the site.  Procedural echocardiographic images do not need to be submitted to the ECL. 
7.6.4 Post-Implant  
Post-implant imaging will be used to confirm any occurrence(s) of worsening of TR severity, 
tricuspid valve and leaflet condition, and any evidence of device embolization, Single Leaflet 
Device Attachment (SLDA), bleeding, perforation, etc. Treatments for these will be per 
physicians’ discretion.  Final TTE and TEE echocardiograms may be acquired and saved by the 
site.   
Immediately following the TriClipTM procedure, heparin (or alternative anticoagulation therapy, 
e.g., bivalirudin) should be discontinued and the ACT should be monitored in accordance with 
hospital protocols.  Vascular sheaths should be removed according to usual hospital practice. 
Post- TriClipTM procedure anticoagulation is recommended per the Investigator’s discretion or as 
described in Section 7.7.3. 
7.7 Post-procedure (Roll-in, Device Group and Single-arm Cohort; In-hospital)  
Subjects will receive standard post-cardiac catheterization procedure care as judged 
appropriate by the Investigator.  Subjects should be advised to limit strenuous physical activity 
for the first month following the TriClipTM procedure or longer, as deemed appropriate by the 
Investigator.  
The medication recommendations below are reflective of the device arm only. For the Control 
group, subjects should be optimized on medical management prior to enrollment. Frequent 
changes to medications in the control group should be avoided and only performed if clinically 
indicated.  
7.8 Discharge (Roll-in, Device Group and Single-arm Cohort) 
Prior to discharge (Discharge occurs when subject leaves the implanting hospital), the following 
required tests and procedures should be completed (> 16 hours post TriClipTM procedure and no 
later than day of discharge) as outlined below, and the information should be captured on the 
appropriate eCRFs: 
• 
12-lead ECG 
• 
Blood draw 
• 
Concomitant cardiovascular medication logs 

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• 
Physical exam including vital signs (weight, heart rate and blood pressure) 
• 
Echocardiogram (TTE)  
• 
Adverse events 
• 
Protocol deviations 
• 
Device deficiency 
• 
NYHA Functional Class assessment 
 
Each subject implanted with a Clip(s) must be provided the Implant Identification Card, included 
in each TriClipTM System package.  The subject must be instructed to keep this Implant 
Identification Card on their person at all times.  The serial number of all implanted TriClipTM (s) 
must be recorded on the Implant Identification Card. 
7.8.1 Post-Procedure Medications 
7.8.1.1 Antibiotic Therapy 
Administer additional intravenous doses of antibiotics at approximately 6 and 12 hours (or per 
institutional guidelines) after the completion of the procedure. 
The Investigator should instruct all subjects who receive the TriClipTM device of the need for 
endocarditis prophylaxis, as recommended in the ACC/AHA 2008 Guideline Update on Valvular 
Heart Disease: Focused Update on Infective Endocarditis.  Subjects should be instructed to 
notify the Investigator or the subject’s primary care physician in the event that a procedure 
recommended by this Guideline is planned, so that prophylactic antibiotics can be prescribed.  A 
prescription for endocarditis prophylaxis may be provided to the subject at discharge. 
7.8.1.2 Antiplatelet/Anticoagulation Therapy 
Following placement of the TriClipTM device, anticoagulation therapy is prescribed.  If a loading 
dose of clopidogrel was not given prior to the TriClipTM procedure, it may be administered after 
the procedure at investigator discretion.  Post- TriClipTM procedure anticoagulation is as follows: 
1. Reinitiate warfarin, dabigatran or factor Xa inhibitor (if discontinued for the TriClipTM 
procedure) at pre-procedure levels or as appropriate.  If chronic oral anticoagulation is 
used, aspirin and clopidogrel use are not recommended, but are allowed if otherwise 
indicated for other conditions. 
2. If chronic oral anticoagulation is not used, it is strongly recommended that either daily 
clopidogrel (75 mg) and/or aspirin (≥75 mg) is administered for 6 months or longer. If 
aspirin is to be used, a loading dose of 325 mg acetylsalicylic acid (ASA) may be 
administered either pre- or immediately post- TriClipTM procedure followed by ≥75 mg 
per day for 6 months or longer at the Investigator’s discretion. 
7.8.1.3 Management of Hypertension 
Subjects should have their blood pressure checked prior to discharge. Subjects should be 
prescribed medication as necessary following current standard of care to maintain normotensive 
blood pressure. 
7.8.1.4 Cardiovascular Medications 
Subjects must continue to take baseline medications without change during follow-up, unless 
clinically (medically) necessary.  If there are any cardiovascular medication changes (including 

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dosage changes), these changes, and the reason for change must be documented on the 
electronic case report form.   
7.9 “Treatment” Visit (Control Group) 
The “Treatment” visit in the Control group must occur between 0 and 14 days after 
randomization.  At the “Treatment” visit, Control group subjects will be seen by the HF specialist 
investigator, and will undergo a physical exam, including vital signs, cardiac health status and 
evaluation of heart failure medications.   
7.10 Follow-up Assessments   
7.10.1 Follow-up CIP Medications  
Subjects must continue to take baseline medications without change during follow-up, unless 
clinically (medically) necessary.  If there are any cardiovascular medication changes (including 
dosage changes), these changes, and the reason for change must be documented on the 
electronic case report form.     
Subjects should have their blood pressure checked. Subjects should be prescribed medication 
as necessary following current standard of care to maintain normotensive blood pressure. 
7.10.2 Follow-up for All Subjects  
Required clinical follow-up will be performed at the following intervals (based on treatment visit) 
for all subjects with TriClipTM procedure attempt, regardless of whether a TriClipTM was 
successfully implanted:  
• 
Discharge post-TriClipTM procedure 
• 
30 days (-3/+14 days) follow-up visit (this visit must be conducted even if subject is in 
hospital) 
• 
6 months (180 days ± 28 days) follow up visit 
• 
1 year (365 days ± 28 days) follow up visit 
• 
18 months (545 days ± 28 days) follow up visit 
• 
2 years (730 days ± 28 days) follow up visit 
• 
3 years (1095 days ± 28 days) follow up visit 
• 
4 years (1460 days ± 28 days) follow up visit 
• 
5 years (1825 days ± 28 days) follow up visit 
 
Follow-up visits will be calculated from the date of the Index Procedure (for subjects receiving 
the device) and the Treatment visit for subjects in the Control group.  Follow-up assessments 
can be performed at any point in the window, and should be conducted, whenever possible, by 
the same individual who performed the baseline tests.  The subject should be followed at the 
investigational site where the subject was enrolled and may be followed at another 
investigational site only with prior agreement from that site’s Investigator and from the Sponsor. 
At the 30-day follow-up visit, the echocardiographer shall examine the integrity of the TriClipTM.   
Subjects must continue to take baseline medications without change during follow-up, unless 
clinically (medically) necessary. If there are any cardiovascular medication changes (including 
dosage changes), these changes should be documented on the electronic case report form. In 
general, neurohormonal antagonists should not be changed. Subjects implanted with the 

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TriClipTM must also be evaluated for device integrity. Required tests and procedures outlined 
below must be completed.  Timing of specific tests will follow the Clinical Evaluation Schedule 
(Table 1) outlined below. These clinical assessments are standard assessments for most 
cardiac/structural heart interventional procedures and therefore should be administered per 
standard of care at each Institution.  All visits and tests must be completed even if the subject is 
in hospital. Refer to the Schedule of Events table section 7.15 for timing of below listed tests. 
• 
12-lead ECG 
• 
Blood draw 
• 
Physical exam including vital signs (weight, heart rate and blood pressure) 
• 
Echocardiogram – TTE at all follow-up visits  
• 
Modified Rankin Scale (Required at visits occurring after onset of stroke)  
• 
6-Minute Walk Test (6MWT)– See APPENDIX XIII for 6 Minute Walk Test Guidelines 
• 
Concomitant cardiovascular medications assessment 
• 
NYHA Functional Class assessment 
• 
KCCQ QoL and SF-36 questionnaires to be completed by the subject – must be 
administered by “blinded” study personnel. Note: To minimize bias and undue 
influence, the QoL questionnaires will be completed by the subject, unless the 
subject is unable to complete the questionnaire on their own (a note to file must be 
completed to document the inability of subject to complete the questionnaire) 
• 
Assess and record adverse events 
• 
Assess and record protocol deviations 
 
All subjects should continue to be monitored and treated per applicable standards of care 
consistent with the subject’s condition.  The site Principal Investigator should collaborate with 
the other site investigators as applicable in determining the treatment strategy for all subjects 
enrolled at their site. The electronic case report forms will document changes in treatment 
strategy (i.e. new use of CRT, PCI, tricuspid valve surgery, and/or mitral valve surgery) and who 
was involved with determining changes in treatment strategy.  Subjects implanted with the Clip 
must be evaluated for device integrity.  
 
7.11 TriClipTM Intervention in Control Group Subjects or Additional TriClipTM 
Intervention in Roll-in, Device Group or Single-arm Cohort Subjects 
Control group subjects will not be allowed to undergo the TriClipTM procedure until after completion 
of the 12-month visit. TriClipTM intervention in the Control group prior to the 12-month visit will be 
considered a major protocol deviation.  Prior to TriClipTM procedure attempt in, a Control group 
subject upon completion of 12-month visit, the subject must be rescreened and evaluated by the 
ECL and EC to assess eligibility. A 30-Day Post-TriClipTM Follow-up visit must be completed 30 
days (-3/+14 days) after the TriClipTM procedure.  This visit should still be completed even if the 
subject is in hospital.  The same assessments shall be performed as done for the 30-day follow-
up. Following the 30-day post procedure visit the patient will continue with their predetermined 
visit schedule. 
It may be necessary for a roll-in, Device group, single-arm, or cross-over subject to undergo 
additional TriClipTM procedures.  A TTE must be performed within 90 days prior to a TriClipTM 
procedure in either group.  A 30-day Post- TriClipTM Follow-up visit must be completed 30 days (-
3/+14 days) after the additional TriClipTM procedure.  This visit should still be completed even if 

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the subject is in hospital.  The same assessments shall be performed as done for the 30-day 
follow-up. If this visit window overlaps with another study follow-up visit window, only one study 
visit is needed to satisfy these requirements.  
7.12 
Tricuspid Valve Surgery 
For inclusion into this trial, all subjects prior to enrollment are expected to be at intermediate or 
greater risk for mortality or morbidity post tricuspid valve surgery. If a subject’s condition 
worsens considerably due to TR (regardless of study arm or group assignment), then the 
subject can undergo tricuspid valve surgery provided that both the heart failure specialist and 
the surgeon deem that tricuspid valve surgery is required. The sponsor will be notified of this 
occurrence. A TTE must be performed within 90 days prior to tricuspid valve surgery and 
provided to the ECL for assessment.     
A 30-Day Post-Tricuspid Valve Surgery Follow-up visit must be completed 30 days (-3/+14 
days) after the tricuspid valve surgery.  This visit should still be completed even if the subject is 
in hospital. If this visit window overlaps with another study follow-up visit window, only one study 
visit is needed to satisfy these requirements. Subjects will continue to be followed per this 
Clinical Investigational Plan. 
7.12.1 30-Day Post-Tricuspid Valve Surgery Follow-up 
Requirements for the 30-day Post-Tricuspid Valve Surgery Follow-up visit are described below. 
• 
12-lead ECG 
• 
Blood draw 
• 
Physical exam including vital signs (weight, heart rate and blood pressure) 
• 
Echocardiogram (TTE) 
• 
Modified Rankin Scale (Assessment of mRS should be performed only after onset of 
stroke, if stroke occurred) 
• 
Concomitant cardiovascular medications assessment 
• 
NYHA Functional Class assessment 
• 
Assess and record adverse events  
• 
Assess and record protocol deviations 
7.13 
Explanted TriClipTM Device  
The TriClipTM device may be explanted during tricuspid valve surgery or an autopsy.  If possible, 
fluoroscopic images with side views of the device should be obtained prior to explant.  Following 
explant of the TriClipTM device(s) during surgery, the subject will continue follow-up schedule 
based on index procedure date.  Explant information will be captured on the Tricuspid Valve 
Surgery Form or Death Form.   
7.14 Patient Reported Outcome (PRO) Measures  
The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a 23-item self-administered 
questionnaire/PRO developed to independently measure the patient’s perception of their health 

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status, which includes heart failure symptoms, impact on physical and social function, and how 
their heart failure impacts their quality of life (QOL) within a 2-week recall period. 
The SF-36 is a 36 item scale constructed to survey health status and quality of life.  The form 
asks participants to reply to questions according to how they have felt in the previous week.  
The SF-36 can be summarized into two summary scores representing physical and mental 
components of health and can also be used to derive health related quality of life index values. 
A blinded coordinator or designee will administer KCCQ and SF-36 questionnaires during the 
follow up visits (30-day visit and afterwards).  KCCQ and SF-36 questionnaires must be 
completed by the subject.  It is important the subject understands the meaning of all words and 
instructions in the questionnaires. The subject should be instructed to ask any questions about 
the questionnaires if further explanation is needed. Once the questionnaires are completed, the 
Coordinator or designee will review for completeness to verify that all questions have been 
answered according to the directions provided. 
To minimize bias and undue influence, the KCCQ and SF-36 questionnaires will be completed 
by the subject, unless the subject is unable to complete the questionnaires on their own (in such 
cases a note to file must be completed to document the inability of subject to complete the 
questionnaire). 
 
 

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c Only required for subjects in the imaging sub study. 
d Only required for sites with capability. 
e Not required at 18 months.  
f Only required at visit after onset of stroke, if stroke occurred. 
g These assessments during these visits should be completed by blinded personnel 
 
 
8 
ADVERSE EVENTS  
To comply with worldwide standards and guidelines on clinical investigation adverse event 
reporting, the Sponsor has adopted uniform and worldwide applicable standard definitions and 
reporting timelines to be used and adhered to by the investigators.   
8.1 Definition  
8.1.1 Adverse Event  
An adverse event (AE) is any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, users or other 
persons, whether or not related to the medical device under investigation.  
As part of ISO 14155 Section 3.2, the Adverse Event definition has the following notes: 
Note 1: This definition includes events related to the medical device under investigation or the 
comparator.  
Note 2: This definition includes events related to the procedures involved.  
Note 3: For users or other persons, this definition is restricted to events related to medical 
devices under investigation.  
8.1.2 Serious Adverse Event  
If the AE meets any of the criteria below, it is regarded as a serious adverse event (SAE).   
  
a) 
Led to a death,  
b) 
Led to a serious deterioration in health of the subject, that either resulted in: 
1. 
a life-threatening illness or injury, or  
2. 
a permanent impairment of a body structure or a body function, or  
3. 
in-patient hospitalization or prolongation of existing hospitalization, or  
4. 
medical or surgical intervention to prevent life threatening illness or injury 
or permanent impairment to a body structure or a body function or 
5. 
chronic disease   
c) 
fetal distress, fetal death or a congenital abnormality or birth defect.  
 
Note: A planned hospitalization for a pre-existing condition, or a procedure required by the CIP, 
without a serious deterioration in health, is not considered to be an SAE.  
8.2 Device Relationship  
Determination of whether there is a reasonable possibility that an investigational product or 
device under investigation caused or contributed to an AE is to be determined by the 
Investigator and recorded on the appropriate CRF form. Determination should be based on 

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assessment of temporal relationships, evidence of alternative etiology, medical/biologic 
plausibility, and patient condition (pre-existing condition).  
8.2.1 Unanticipated (Serious) Adverse Device Effect [U(S)ADE] 
U(S)ADE refers to any serious adverse effect on health or safety or any life-threatening problem 
or death caused by, or associated with, a device, if that effect, problem, or death was not 
previously identified in nature, severity, or degree of incidence in the investigational plan or 
application (including a supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare of subjects. 
8.2.2 Device Deficiency/Device Malfunction 
Device deficiency is defined as an inadequacy in the identity, quality, durability, reliability, 
usability, safety of performance of an investigational device including malfunction,  use errors, or 
inadequacy in the information supplied by the manufacturer including labeling. This includes the 
failure of the device to meet its performance specifications or otherwise perform as intended.  
Note 1: The definition includes device deficiencies related to investigational medical device or 
the comparator. 
Note 2: Cyber-security incidents related to the investigational product, shall be reported as 
device deficiencies 
 
A device malfunction is the failure of an investigational medical device to perform in accordance 
with its intended purpose when used in accordance with the instructions for use or CIP, or IB.  
8.3 Adverse Event and Device Deficiency/Device Malfunction Reporting  
8.3.1 Adverse Event Reporting  
Safety surveillance and reporting starts as soon as the patient is enrolled in the clinical 
investigation. Safety surveillance and reporting will continue until the last follow-up visit has 
been performed, the subject is deceased, the subject concludes participation in the clinical 
investigation, or the subject withdraws from the clinical investigation. All adverse event data, 
including deaths and device deficiency data, will be collected throughout the time period defined 
above and will be reported to the Sponsor on an eCRF within an Electronic Data Capture (EDC) 
database. Additional information, with regard to an adverse event, should be updated on the 
appropriate eCRF within the EDC.   
Unchanged, chronic, non-worsening or pre-existing conditions are not AEs and should not be 
reported. 
Non-cardiac related abnormal laboratory values will not be considered AEs unless:  
1) the investigator determined that the value is clinically significant,  
2) the abnormal lab value required intervention, or  
3) the abnormal lab value required subject termination from the study. 
An offline form will be made available to allow the investigator to report SAEs in the event the 
entry cannot be made in the EDC. This does not replace the EDC reporting system. All 
information must still be entered into the EDC system as soon as feasible.  

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SAE Reporting  
The investigator must report all SAEs to the Sponsor as soon as possible but no later than 
outlined below.  
Clinical Site  
Reporting timelines  
All Sites  
SAEs must be reported to the Sponsor no later than 3 calendar days from the  
day the site personnel became aware of the event or as per the investigative  
site’s local requirement, if the requirement is more stringent than those outlined.  
 
Sites must record the date the site staff became aware that the event met the criteria of an SAE 
in the source document.  The Investigator will further report the SAE to the local IRB/EC 
according to the institution’s IRB/EC reporting requirements. 
8.3.2 Unanticipated Serious Adverse Device Effect Reporting to Sponsor and IRB 
The Sponsor requires the Investigator to report any USADE to the Sponsor within 3 calendar 
days of the investigator’s knowledge of the event, unless local requirements are more stringent, 
and to the IRB/EC per IRB/EC requirements. 
8.3.3  Device Deficiency/Malfunction Reporting  
Sites should report all device deficiencies/malfunctions should be reported on the appropriate 
eCRF form.  
The investigator must report all device deficiencies/malfunctions to the Sponsor as soon as 
possible but no later than outlined below.  
Clinical Sites 
Reporting timelines 
All Sites 
Sites must report device deficiencies/malfunctions to the Sponsor no 
later than 3 calendar days from the day the site personnel became 
aware of the event or as per the investigative site’s local 
requirements, if the requirement is more stringent than those outlined. 
 
Sites must report device deficiencies/malfunctions to the IRB/EC per the investigative site’s local 
requirements. 
 
Sites should return the device, if not implanted or not remaining in the subject, to the Sponsor.   
Device deficiencies/malfunctions should be reported to the IRB/EC per the investigative site’s 
local requirements. 
 
An offline form will be made available to allow the investigator to report device 
deficiencies/malfunctions in the event that the entry cannot be made in the EDC system. This 
does not replace the EDC reporting system. All information must still be entered in the EDC 
system as soon as feasible.   

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9.2.1.2.4 Change in 6MWT at 12 Months over Baseline 
Improvement in the 6MWT at 12 months from baseline is an important secondary effectiveness 
endpoint in the comparison of the Device group to the Control group.  
The null and alternative hypotheses are stated as:  
H0: 𝜇𝜇𝐷𝐷, ∆6MWD −𝜇𝜇𝐶𝐶, ∆6MWD = 0 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
  
9.2.1.2.5 Recurrent HF Hospitalizations at 24 Months  
Treatment with the TriClipTM device is expected to reduce the risk of recurrent HF 
hospitalizations. The null and alternative hypotheses are stated as: 
 
  
 
 
 
 
 
 
 
  
 
  
The endpoint will be assessed when all subjects complete 24 months of follow-up. All available 
follow-up through 24 months at the time of data cut-off will be included in the analysis. Subjects 
who do not experience any HF hospitalizations will be censored on their data cut-off date. 

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9.11 Deviations from Statistical Plan  
 
 
    
 
10 DIRECT ACCESS TO SOURCE DATA/DOCUMENTS  
The investigator/institution will permit direct access to source data/documents for the purpose of  
performing clinical investigation-related monitoring, audits, IRB/EC review and regulatory 
inspections. 
Subjects providing informed consent are agreeing to allow clinical investigation monitors or 
regulatory authorities, including foreign countries, to review in confidence any records identifying 
the subjects in this clinical investigation. This information may be shared with regulatory 
agencies; however, Sponsor undertakes not to otherwise release the subject's personal and 
private information. 
11 QUALITY CONTROL AND QUALITY ASSURANCE  
11.1 Selection of Clinical Sites and Investigators  
The Sponsor will select investigators qualified by training and experience to participate in the 
clinical investigation. Sites will be selected based upon review of a recent site assessment, if 
applicable, and the qualifications of the investigators who will participate in the clinical 
investigation. 
 
11.2 Site Principal Investigator Responsibilities 
The role of the Site Principal Investigator is to implement, oversee the management of the day-
to-day conduct of the clinical investigation as well as ensure data integrity and the rights, safety 
and well-being of the subjects involved in the clinical investigation. The principal investigator 
shall support monitoring and reporting to IRB/EC and local competent authorities as necessary, 
throughout the conduct of the clinical investigation. 
The principal investigator is responsible for ensuring adequate training and qualification of the 
investigation site team and for maintaining oversight of their activities. The principal investigator 
may delegate tasks to members of the investigation site team but retains responsibility for the 
clinical investigation. This also applies when activities are outsourced to an external 
organization by the principal investigator in which case he/she shall exercise oversight to ensure 
the integrity of all tasks performed and any data generated by this external organization. 
 
 
11.3  Clinical Investigation Finances and Agreements 
 
Abbott will finance the clinical investigation and will compensate investigational sites for 
participation in the clinical investigation per the conditions of agreement between Abbott and the 
investigational site. 

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11.4 CIP Amendments   
The Sponsor will provide approved CIP amendments to the prior to implementing the 
amendment. The Principal Investigator is responsible for notifying the IRB/EC or equivalent 
committee of the CIP amendment (administrative changes) or obtaining IRB’s/EC’s approval of 
the CIP amendment (changes in subject care or safety), according to the instructions provided 
by the Sponsor with the CIP amendment. 
Sites must document in writing acknowledgement/approval of the CIP amendment by the IRB/EC 
prior to implementation of the CIP amendment. Sites must also provide copies of this 
documentation to the Sponsor. 
11.5 Training  
All Investigators and clinical investigation personnel are required to attend Sponsor training 
sessions, which may be conducted at an Investigator's meeting, a site initiation visit or other 
appropriate training sessions.  Over-the-phone, web-based or self-training may take place as 
required. Training of Investigators and clinical investigation personnel will include, but is not 
limited to, the CIP requirements, investigational device usage (if applicable),) echocardiographic 
imaging, electronic case report form completion and clinical investigation personnel 
responsibilities.  All Investigators and clinical investigation personnel that are trained must sign 
a training log (or an equivalent) upon completion of the training. Prior to signing the training log, 
Investigators and clinical investigation personnel must not perform any CIP-related activities that 
are not considered standard of care at the site.   
11.6 Monitoring   
Sponsor and/or designee will monitor the clinical investigation over its duration according to the 
CIP-specific monitoring plan which will include the planned extent of source data verification. 
Prior to initiating any procedure, the Sponsor monitor (or delegate) will ensure that the following 
criteria are met: 
• 
The Principal investigator understands and accepts the obligation to conduct the clinical 
investigation according to the CIP and applicable regulations, and has signed the 
Investigator Agreement [for US clinical investigations] or the Clinical Trial Agreement [for 
OUS clinical investigations].   
• 
The Investigator and his/her staff should have sufficient time and facilities to conduct the 
clinical investigation and should have access to an adequate number of appropriate 
subjects to conduct the clinical investigation.   
• 
Source documentation (including original medical records) must be available to 
substantiate proper informed consent procedures, adherence to CIP procedures, 
adequate reporting and follow-up of adverse events, accuracy of data collected on case 
report forms, and device information.   
• 
The Investigator/site will permit access to such records. A monitoring visit log will be 
maintained at the site. The Investigator will agree to dedicate an adequate amount of 
time to the monitoring process. The Investigator and/or research coordinator will be 
available for monitoring visits. It is expected that the Investigator will provide the monitor 

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with a suitable working environment for review of clinical investigation-related 
documents. 
11.7 Deviations from CIP  
The Investigator should not deviate from the CIP for any reason except in cases of medical 
emergencies when the deviation is necessary to protect the rights, safety and well-being of the 
subject or eliminate an apparent immediate hazard to the subject. In that event, the Investigator 
will notify Sponsor immediately by phone or in writing.   
No waivers for CIP deviations will be granted by the Sponsor.  All deviations must be reported to 
the Sponsor using the Deviation CRF. The occurrence of CIP deviations will be monitored by 
the Sponsor for evaluation of investigator compliance to the CIP and regulatory requirements 
and dealt with according to written procedures. Investigators will inform their IRB/EC or 
equivalent committee of all CIP deviations in accordance with their specific IRB/EC or 
equivalent committee reporting policies and procedures.   
In the event of repeated non-compliance, as determined by the Sponsor, a Sponsor’s monitor or 
company representative will attempt to secure compliance by one or more of the following (and 
not limited to):   
• 
Visiting the investigator and/or delegate  
• 
Telephoning the investigator and/or delegate  
• 
Corresponding with the investigator and/or delegate  
Repeated non-compliance with the signed agreement, the CIP or any other conditions of the 
clinical investigation may result in further escalation in accordance with the Sponsor’s written 
procedures, including securing compliance or, at its sole discretion, Sponsor may terminate the 
investigator's participation in the clinical investigation.   
11.8 Quality Assurance Audit  
A Sponsor representative or designee may request access to all clinical investigation records, 
including source documentation, for inspection during a Quality Assurance audit. 
In the event that an investigator is contacted by a Regulatory Agency in relation to this clinical 
investigation, the Investigator will notify Sponsor immediately. The Investigator and Research 
Coordinator must be available to respond to reasonable requests and audit queries made during 
the audit process. The Investigator must provide Sponsor with copies of all correspondence that 
may affect the review of the current clinical investigation (e.g., Form FDA 483, Inspectional 
Observations, Warning Letters, Inspection Reports, etc.). Sponsor may provide any needed 
assistance in responding to regulatory audits. 
11.9 Committees 
11.9.1 Steering Committee   
The Steering Committee is responsible for overseeing the scientific and operational aspects of 
the clinical investigation. This committee will meet regularly to monitor subject enrollment, 
general data collection and non-compliance with the CIP at individual centers, to review and act 
upon recommendations of the Data Monitoring Committee (DMC), to review operational issues 

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that may arise and warrant a CIP amendment or other corrective action and to determine policy 
regarding any publications arising from data generated from the performance of the clinical 
investigation. 
11.9.2 Publications Committee  
A Publication Committee shall be established to oversee clinical investigations publications, 
including publication planning and authorship determinations. Publication Committee 
membership may include members of the Steering Committee, Principal Investigators, a 
representative of the Sponsor and a statistician. The Publication Committee will determine 
policy and strategies regarding individual presentations and/or publications arising from clinical 
investigation generated data. The committee will also review all external requests for accessing 
clinical investigation-related data and strategies aligning with the Sponsor’s presentation and 
publication team expectations. The committee will also follow the Sponsor’s applicable policies 
and Standard Operating Procedures.  
11.9.3 Data Monitoring Committee (DMC)  
The DMC is an independent multidisciplinary group restricted to individuals free of significant 
conflicts of interest. The source of these conflicts may be financial, scientific, or regulatory in 
nature. The DMC will be composed of at least two physicians with experience relevant to the 
clinical investigation and a biostatistician.    
The DMC will serve in an advisory role to the Sponsor by reviewing cumulative data from the 
clinical investigation at prescribed intervals for the purpose of safeguarding the interests of 
enrolled subjects and those patients yet to be enrolled, as well as the continuing validity and 
scientific merit of the clinical investigation. The committee composition, frequency of meetings, 
and the data monitoring report guidelines are described in the DMC Charter.  
The DMC may consider a recommendation for modifications or termination of the clinical 
investigation based on any perceived safety concerns regardless of statistical significance. The 
recommendations of the DMC are not binding, and all final decisions related to clinical 
investigation modifications rest with Abbott and the Steering Committee. 
11.9.4 Clinical Events Committee (CEC)  
The CEC is an independent adjudication body comprised of qualified physicians who are not 
participants in the clinical investigation. The CEC will review and adjudicate prespecified events 
reported by investigators or identified by Safety personnel for the clinical investigation as 
defined in the CEC charter and according to definitions provided in this CIP.    
11.9.5 Eligibility Committee 
The EC consisting of a Heart Failure Specialist, Implanters (Interventional Cardiologist and 
Cardiac Surgeon) and an Echocardiologist reviews data provided by the investigational site and 
echo data from the echo core laboratory, and conducts clinical assessment.  The EC finally 
decides whether a patient can be enrolled in the clinical trial or not, and whether they will be in 
the Randomized or Single-arm.  

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11.9.6 Imaging Committee 
The Imaging Committee will consist of imaging experts in the field of Echocardiography and 
Radiology. Members will meet as required and provide input on determining imaging criteria as 
well as provide oversite on the imaging sub-study. 
12 DATA HANDLING AND RECORD KEEPING   
Sponsor and/or its affiliates will maintain documentation of the systems and procedures used in 
data collection for the duration of the clinical investigation.  CRF data collection will be 
performed through a secure web portal and only authorized personnel will access the EDC 
system using a unique username and password to enter, review or correct data. Passwords and 
electronic signatures will be strictly confidential.   The data will be subjected to consistency and 
validation checks within the EDC system and supplemental review by the Sponsor. 
At the conclusion of the clinical investigation, completed CRF images with the date-and-time 
stamped electronic audit trail indicating the user, the data entered, and any reason for change (if 
applicable) will be provided to the investigational sites, if requested.   
 For the duration of the clinical investigation, the Investigator will maintain complete and 
accurate documentation including, but not limited to, medical records, clinical investigation 
progress records, laboratory reports, CRFs, signed ICFs, device accountability records (if 
applicable), correspondence with the IRB/EC and clinical investigation monitor/Sponsor, 
adverse event reports, and information regarding subject discontinuation or completion of the 
clinical investigation.   
12.1 Protection of Personally Identifiable Information  
The Sponsor respects and protects personally identifiable information collected or maintained 
for this clinical investigation.  
The Sponsor implements technical and physical access controls to ensure that Personal 
Information is accessible only to and processed only on a ‘need to know’ basis, including 
periodic review of access rights, and revocation of access when an individual’s employment is 
terminated or the individual transitions to a role that does not require access to Personal 
Information, and appropriate restrictions on physical access to premises, facilities, equipment, 
and records containing Personal Information. 
The Sponsor requires the investigational sites to transfer into Sponsor’s data management 
systems only pseudonymous Personal Information (key-coded) necessary to conduct the 
Clinical Investigation, such as the patient’s medical condition, treatment, dates of treatment, etc. 
The Sponsor discloses as part of the clinical investigation informed consent process that some 
Sponsor representatives still may see Personal Information at the participating sites for 
technical support of the participating physicians on the device implant or procedures, monitoring 
and quality control purposes. Confidentiality of Personal Information will be observed by all 
parties involved at all times throughout the clinical investigation. The privacy of each subject and 
confidentiality of his/her information will be preserved in reports and when publishing any data. 
The Sponsor data management systems and processes were designed, developed, and tested 
according to industry standards to appropriately safeguard Confidential Information (including 

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any Personal Information) against unauthorized access and/or interference by third parties, 
intrusion, theft, destruction, loss or alteration. Clinical Investigation data are encrypted in transit 
and at rest.  
The Sponsor maintains a Privacy Incident procedure that complies in all respects with 
Applicable Law and industry best practices. 
12.2  Data Management Plan  
A Data Management Plan (DMP) will describe procedures used for data review, data cleaning, 
and issuing and resolving data discrepancies. If appropriate, the DMP may be updated 
throughout the duration of the clinical investigation. All revisions will be tracked and document 
controlled. 
12.3 Source Documentation   
Regulations and GCP require the Investigator to maintain information in the subject’s original 
medical records that corroborates data collected on the CRFs. In order to comply with these 
regulatory requirements/GCP, the following information should be included in the subject record 
at a minimum and if applicable to the clinical investigation:  
• 
Medical history/physical condition of the subject before involvement in the clinical 
investigation sufficient to verify CIP entry criteria  
• 
Dated and signed notes on the day of entry into the clinical investigation referencing the 
Sponsor, CIP number, subject ID number and a statement that informed consent was 
obtained  
• 
Dated and signed notes from each subject visit (for specific results of procedures and 
exams)  
• 
Adverse events reported and their resolution, including supporting documents, such as 
discharge summaries, catheterization laboratory reports, ECGs, and lab results including 
documentation of site awareness of SAEs and of investigator assessment of device 
relationship for SAEs.  
• 
CIP-required laboratory reports and 12-lead ECGs, reviewed and annotated for clinical 
significance of out of range results (if applicable).   
Note: With electronic medical records some clinical sites may be able to annotate that the labs 
or ECG have been reviewed in the system. For those sites that do not have such capability, the 
labs or ECG may be able to be printed or signed.  
• 
Notes regarding CIP-required and prescription medications taken during the clinical 
investigation (including start and stop dates)  
• 
Subject’s condition upon completion of or withdrawal from the clinical investigation  
• 
Any other data required to substantiate data entered into the CRF 
12.4 Case Report Form Completion   
Primary data collection based on source-documented hospital and/or clinic chart reviews will be 
performed clearly and accurately by site personnel trained on the CIP and CRF completion. The 
investigator will ensure accuracy, completeness, legibility and timeliness of the data reported to 
the Sponsor on the CRFs and in all required reports.   

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Data on CRFs will be collected for all subjects who sign an informed consent form, including 
subjects who may not meet all inclusion/exclusion criteria during screening, prior to 
randomization.  
Only authorized site personnel will be permitted to enter the CRF data through the EDC system 
deployed by the Sponsor. An electronic audit trail will be used to track any subsequent changes 
of the entered data. 
12.5 Record Retention  
The Sponsor and Investigator/Site will archive and retain all documents pertaining to the clinical 
investigation as per the applicable regulatory record retention requirements. The Investigator 
must obtain permission from Sponsor in writing before destroying or transferring control of any 
clinical investigation records. 
12.6 Investigational Devices Accountability (Applicable for US and Canada Only)  
The Sponsor ships investigational products only to the Principal Investigator (the responsible 
leader of the investigational site) or his/her legal designee of each site, after sites receive 
documentation of site activation and shipping authorization is complete.    
The Investigator or an authorized designee must maintain adequate records of the receipt and 
disposition of each investigational device, including part number, batch number, and serial 
number (if applicable), date used, subject identification, and treating physician.  
Storage locations for the devices at investigational sites must be locked with access restricted 
only to investigators and authorized personnel. 
   
Inventory Accountability Log supplied by the Sponsor will be used. The Inventory Accountability 
Log must document the disposition of all investigational devices including those that have been 
returned to Sponsor.  
All investigational devices that are associated with a device failure or device deficiency must be 
returned immediately to the Sponsor.  
13 ETHICAL CONSIDERATION  
 
13.1 Institutional Review Board/Medical Ethics Committee Review and Approval  
Institutional Review Board (IRB)/Ethics Committee approval for the CIP, ICF and other written 
information provided to the patient will be obtained by the Principal Investigator at each 
investigational site prior to consenting and enrolling patients in this clinical investigation. The 
approval letter must be received prior to the start of this clinical investigation and a copy must 
be provided to the Sponsor.   
Any amendments to the CIP as well as associated ICF changes will be submitted to the IRB/ 
Ethics Committee and written approval obtained prior to implementation, according to each 
institution’s IRB/Ethics Committee requirements.  
No changes will be made to the CIP or ICF or other written information provided to the patient 
without appropriate approvals, including IRB/Ethics Committee, the Sponsor, and the regulatory 
agencies (if applicable). 

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Until the clinical investigation is completed, the Investigator will advise his/her IRB/EC of the 
progress of this clinical investigation, per IRB/Ethics Committee requirements. Written approval 
must be obtained from the IRB/Ethics Committee yearly to continue the clinical investigation, or 
according to each institution’s IRB/Ethics Committee requirements.   
No investigative procedures other than those defined in this CIP will be undertaken on the 
enrolled subjects without the written agreement of the IRB/Ethics Committee and the Sponsor. 
14 CLINICAL INVESTIGATION CONCLUSION  
The clinical investigation will be concluded when:  
• 
All sites are closed AND  
• 
The final report has been provided to investigators or the Sponsor has provided formal 
documentation of clinical investigation closure. 
The sponsor will submit the clinical investigation report within one year of the end of the 
investigation. 
15 PUBLICATION POLICY  
The data and results from the clinical investigation are the sole property of the Sponsor. The 
Sponsor shall have the right to access and use all data and results generated during the clinical 
investigation. The Investigators will not use this clinical investigation-related data without the 
written consent of the Sponsor for any purpose other than for clinical investigation completion or 
for generation of publication materials, as referenced in the Clinical Trial Agreement. Single-
center results are not allowed to be published or presented before the multi-center results. Any 
proposals for publications or presentations by the investigators must be reviewed and approved 
by the Sponsor in a timely manner to enable Sponsor review in compliance with the Sponsor’s 
publication policy set forth in the Clinical Trial Agreement.  
Upon receiving IDE approval from the FDA, the Sponsor will be responsible for registering this 
clinical investigation on www.clinicaltrials.gov or any other clinical trials, in accordance with the 
International Committee of Medical Journal Editors guidelines, or any other applicable 
guidelines.  Sponsor shall be responsible for any such registration and results posting as 
required by the ClinicalTrials.gov website. Institution and/or Principal Investigator(s) shall not 
take any action to register the clinical investigation. A full report of the pre-specified outcomes, 
regardless of the results, will be made public through the ClinicalTrials.gov website no later than 
12 months after clinical investigation completion, as required by section 801 of the FDA 
Amendments Act. If this clinical investigation is terminated early, the Sponsor will make every 
effort to hasten the release of the pre-specified outcomes through the ClinicalTrials.gov website. 
 
16 RISK ANALYSIS  
  
16.1 Anticipated Clinical Benefits  
There are no guaranteed clinical benefits associated with participation in this clinical 
investigation.  It is expected that patients participating in this trial will experience the same 

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benefit that were observed from an ongoing trial with the TriClipTM device. These benefits 
include, but may not be limited to, the following: 
• 
Reduction in heart failure hospitalization rate 
• 
Improved symptomatic status and quality of life  
• 
A potential for reduced mortality 
16.2 Foreseeable Adverse Events and Anticipated Adverse Device Effects  
Risks associated with the specified device and procedure, together with their likely incidence, 
are described in the IFU and Appendix V.  There may be risks related to the device under 
investigation that are unknown at present.  Likewise, the exact frequency of the risk may be 
unknown.  
16.3 Residual Risks Associated with the Device Under Investigation, as Identified 
in the Risk Analysis Report  
Risk analysis for the TriClipTM device has been performed in accordance with the Risk Analysis 
Plan. The risk analysis utilizes Failure Mode Effect Analysis (FMEA) tool to systematically 
identify potential hazards associated with the process, design, components and use of the 
devices.   Based upon the preclinical, clinical and bench-testing data, all risks have been 
identified and determined to be within acceptable levels. The benefit of treating patients with 
TriClipTM device outweigh the potential risks. 
16.4 Risks Associated with Participation in this Clinical Investigation  
Protocol required assessments are summarized in Section 7.15, Table 1, Clinical Visits and 
Schedule of Assessments. Most of these clinical assessments are standard for most 
cardiac/structural heart interventional procedures and are administered per the standard of care 
at each institution, and do not constitute an additional risk for the clinical investigation participants. 
Study specific assessments that may not be considered standard of care include protocol 
required transesophageal echocardiography (TEE) assessments performed at screening, 
baseline and during protocol defined follow up visits.  TEE is a commonly used safe technique 
in cardiac interventions that requires conscious sedation or general anesthesia, depending on 
hospital standard practice. In the exceptional occasion if complications arise during the TEE 
procedure, it may be necessary to convert to an open surgical procedure. Emergency surgical 
back-up should be available as per the institution’s standard procedures. 
16.5 Possible Interactions with Protocol-Required Concomitant Medications (if 
applicable)  
All medications at baseline and post -procedure (Section 7.8.1) are administered per the current 
guidelines and are standard of care. Although are no protocol -required medications being used 
as part of this study, post-procedure antiplatelet/anticoagulation therapy and prophylactic 
antibiotics for endocarditis as per the standard care (refer to section 7.8.1) are highly 
recommended. The risks associated with these medications are described in the drug summary 
of product characteristics. 

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16.6 Steps Taken to Control or Mitigate Risks  
In-depth recommendations, special precautions and instructions regarding patient selection, 
device handling, device placement and system removal are included in the IFU.  It is also stated 
in the IFU that the devices can only be used by physicians who have received appropriate 
training on how to use the device. This statement is interpreted to mean that the physician users 
are expected to be aware of the known and foreseeable safety risks associated with the use of 
the devices including the surgical and/or non-surgical treatment of these conditions. Each 
site/investigator will have access to the IFU.   
All investigators involved in the conduct of the clinical investigation will be qualified by 
education, training, or experience to perform their tasks and this will be documented 
appropriately.  Patients enrolled in the trial will be selected based on the eligibility criteria 
defined in section 6.3. 
Risks associated with the use of the TriClipTM device are minimized through device design. The 
Delivery System is comprised of the Steerable Sleeve, Delivery Catheter and Implant. The 
Delivery Catheter is designed to deliver and deploy the Implant. Acceptable performance of the 
TriClipTM device was confirmed in bench studies.  
 
16.7 Risk to Benefit Rationale  
TR results from failure of the tricuspid valve to close completely during systole.  The symptoms 
of TR are not evident until the condition has significantly worsened.   Medical therapy for TR is 
directed towards reducing symptoms by decreasing the fluid overload. Many patients are 
refractory to medical therapy and continue to suffer.  Tricuspid valve surgery is only 
recommended as a Class I recommendation when the patient is undergoing left sided heart 
surgery. Isolated tricuspid valve surgery carries a high mortality rate.  
The TriClipTM device was studied in TRILUMINATE trial (CE Mark trial) which has demonstrated 
clinically meaningful reduction in tricuspid valve regurgitation, functional status and quality of life 
at 30 days post procedure. The study has demonstrated good safety profile with no acute 
mortality, no major cardiac AEs, low re-intervention for TR and low procedural AEs such as 
endocarditis and pericardial effusion.  Treatment with TriClipTM Device offers a percutaneous, 
minimally invasive, safe option to reduce TR with short recovery time, amelioration of symptoms 
and improvement in cardiac function and quality of life in patients with severe TR.   
Based on the clinical experience, and bench data, the benefit of TR reduction and improvement 
of TR symptoms with TriClipTM device outweighs any potential risk associated with this 
procedure. 
 
 

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17 APPENDIX I: ABBREVIATIONS AND ACRONYMS  
6MWT– Six Minute Walk Test 
AE – Adverse Event 
APS – Acute Procedural Success 
CRO – Contract Research Organization 
CRF – Case Report Form 
CRT or CRT-D – Cardiac Resynchronization Therapy Device 
CV - Cardiovascular 
CVA – Cerebrovascular Accident 
DBP – Diastolic Blood Pressure 
DD or DM – Device Deficiency or Device Malfunction 
DMC – Data Monitoring Committee 
EC – Eligibility Committee 
ECL – Echocardiographic Core Laboratory 
eCRF – Electronic Case Report Form 
EDC – Electronic Data Capture 
EFS – Early Feasibility Study 
EROA – Effective Regurgitant Orifice Area 
ESC – European Society of Cardiology 
FDA – Food and Drug Administration 
HF – Heart Failure 
IB – Investigator Brochure 
ICD - Implantable cardioverter-defibrillator 
ICF – Informed Consent Form 
IFU - Instructions for Use 
IRB – Institutional Review Board 
IVC – Inferior Vena Cava 
KCCQ – Kansas City Cardiomyopathy Questionnaire 
LVEDV – Left Ventricle End Diastolic Volume 

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LVESV – Left Ventricle End Systolic Volume 
LVEF – Left Ventricular Ejection Fraction 
MAE – Major Adverse Event 
MI – Myocardial Infarction 
MR – Mitral Regurgitation 
NYHA – New York Heart Association 
PAP – Pulmonary Artery Pressure 
PISA – Proximal Isovelocity Surface Area 
QoL – Quality of Life 
RA – Right Atrium 
RV – Right Ventricle 
RVEDD - Right Ventricular End Diastolic Dimension 
RVEF - Right Ventricular Ejection Fraction 
RVSP - Right Ventricular Systolic Pressure 
SBP – Systolic Blood Pressure 
SF-36 – Short Form 36 
SLDA – Single Leaflet Device Attachment 
STS – Society of Thoracic Surgery 
TAPSE - Tricuspid Annular Plane Systolic Excursion 
TEE – Trans-esophageal Echocardiogram 
TR – Tricuspid Regurgitation 
TTE – Transthoracic Echocardiogram 
VC – Vena Contracta   
 

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18 APPENIX II: DEFINITIONS  
ANTICIPATED ADVERSE EVENT 
Derived from ISO14155, MEDDEV 2.7.3: an effect which by its nature, incidence, severity or 
outcome has been previously identified as in the IFU or CIP (Appendix V). 
ASCITES 
The accumulation of fluid in the peritoneal cavity, causing abdominal swelling. 
ATRIAL FIBRILLATION (AF) 
Per Heart Rhythm Society Guidelines 
• 
Paroxysmal: Recurrent (≥ 2) atrial fibrillation episodes that terminate spontaneously 
within 7 days. 
• 
Persistent:  Atrial fibrillation that is sustained beyond 7 days, or lasting less than 7 days 
but necessitating pharmacologic or electrical cardioversion. 
• 
Longstanding Persistent AF: Continuous atrial fibrillation of greater than 1 year 
duration. 
• 
Permanent:  Atrial fibrillation in which cardioversion has failed or not been attempted.  
BNP/NT-proBNP 
B-type natriuretic peptide (BNP) is a hormone produced by your heart. N-terminal (NT)-pro 
hormone BNP (NT-proBNP) is a non-active prohormone that is released from the same 
molecule that produces BNP. Both BNP and NT-proBNP are released in response to changes in 
pressure inside the heart. These changes can be related to heart failure and other cardiac 
problems. Levels goes up when heart failure develops or gets worse, and levels goes down 
when heart failure is stable. In most cases, BNP and NT-proBNP levels are higher in patients 
with heart failure than people who have normal heart function. 
CARDIOGENIC SHOCK  
Sustained SBP ≤90 mmHg for >30 min or the need for intervention (vasopressors/inotropes 
etc.) to maintain SBP >90 mm Hg 
DEATH (All Cause) 
All deaths regardless of cause. Death is further divided into 2 categories 
1. CARDIOVASCULAR DEATH (VARC-2) 
Per the Valve Academic Research Consortium (VARC-2) as any one of the following: 
• 
Any death due to proximate cardiac cause (e.g. MI, cardiac tamponade, worsening 
heart failure) 
• 
Unwitnessed death and death of unknown cause 
• 
All procedure-related deaths, including those related to a complication of the 
procedure or treatment for a complication of the procedure 

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• 
Death caused by non-coronary vascular conditions such as cerebrovascular disease, 
pulmonary embolism, ruptured aortic aneurysm, dissecting aneurysm, or other 
vascular disease 
• 
All valve-related deaths including structural or non-structural valve 
• 
dysfunction or other valve-related adverse events 
 
2. NON-CARDIOVASCULAR DEATH 
Any death in which the primary cause of death is clearly related to 
another condition (e.g. trauma, cancer, suicide)  
DEVICE EMBOLIZATION 
Detachment of the deployed TriClipTM from the tricuspid leaflets as assessed by the study site. 
Diagnosis and management of any occurrence or suspected occurrence of device embolization 
will be per the site investigator’s best medical judgment.  Some recommendations for clinical 
diagnosis and management of device embolization include but are not necessarily limited to 
those outlined below: 
• 
Diagnosis:  
o Observation of patient’s clinical symptoms,  
o Assessment of Clip status via TTE examination of valve, and/or  
o Fluoroscopy and/or x-ray imaging. 
• 
Management will depend on the specific patient’s clinical situation and will be determined 
by the site investigator’s best medical judgment including assessment of overall risks and 
benefits of further intervention.  Some methods of management to consider are:  
o Continued regular clinical monitoring of the patient and the embolized device; 
o Transcatheter manipulation method(s) to stabilize device position;  
o Removal through percutaneous approach and/or  
o Removal through surgical approach. 
 
DEVICE THROMBOSIS 
Formation of an independently moving thrombus on any part of the TriClipTM evidenced by 
echocardiography or fluoroscopy.  If the TriClipTM is explanted or an autopsy is performed, this 
diagnosis should be confirmed. 
ENDOCARDITIS 
A diagnosis of endocarditis based on the following modified Duke criteria, from Infective 
Endocarditis (IE) in Adults: Diagnosis, Antimicrobial Therapy, and Management of 
Complications: A Scientific Statement for Healthcare Professionals From the American Heart 
Association. Circulation. 2015 Oct 13;132(15):1435-86. 
 
Endocarditis is based on the confirmation of either Pathological Criteria or Clinical Criteria below 
in the table.   

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Definite IE 
 Pathological criteria 
  Microorganisms demonstrated by culture or histological examination of a vegetation, a 
vegetation that has embolized, or an intracardiac abscess specimen; or pathological lesions; 
vegetation or intracardiac abscess confirmed by histological examination showing active 
endocarditis 
 Clinical criteria 
  2 Major criteria, 1 major criterion and 3 minor criteria, or 5 minor criteria 
Possible IE 
 1 Major criterion and 1 minor criterion, or 3 minor criteria 
Rejected 
 Firm alternative diagnosis explaining evidence of IE; or resolution of IE syndrome with antibiotic 
therapy for ≤4 d; or no pathological evidence of IE at surgery or autopsy with antibiotic therapy 
for ≤4 d; or does not meet criteria for possible IE as above 
 
Clinical Criteria 
 
Major Criteria 
 
Blood culture positive for IE 
  
Typical microorganisms consistent with IE from 2 separate blood cultures: Viridans 
streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or 
community-acquired enterococci in the absence of a primary focus, or microorganisms 
consistent with IE from persistently positive blood cultures defined as follows: at least 2 
positive cultures of blood samples drawn >12 h apart or all 3 or a majority of ≥4 separate 
cultures of blood (with first and last sample drawn at least 1 h apart) 
  
Single positive blood culture for Coxiella burnetii or anti–phase 1 IgG antibody titer 
≥1:800 
  
Evidence of endocardial involvement 

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Echocardiogram positive for IE (TEE recommended for patients with prosthetic valves, 
rated at least possible IE by clinical criteria, or complicated IE [paravalvular abscess]; 
TTE as first test in other patients) defined as follows: oscillating intracardiac mass on 
valve or supporting structures, in the path of regurgitant jets, or on implanted material in 
the absence of an alternative anatomic explanation; abscess; or new partial dehiscence 
of prosthetic valve or new valvular regurgitation (worsening or changing or pre-existing 
murmur not sufficient) 
 
Minor Criteria 
Predisposition, predisposing heart condition, or IDU 
  
Fever, temperature >38°C 
  
Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic 
aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions 
  
Immunological phenomena: glomerulonephritis, Osler nodes, Roth spots, and 
rheumatoid factor 
  
Microbiological evidence: positive blood culture but does not meet a major criterion as 
noted above (excludes single positive cultures for coagulase-negative staphylococci and 
organisms that do not cause endocarditis) or serological evidence of active infection with 
organism consistent with IE 
 
ETIOLOGY OF TRICUSPID REGURGITATION 
Will be determined as Degenerative, Functional, or Lead-Induced.  
• 
Degenerative Tricuspid Regurgitation 
Tricuspid regurgitation primarily due to abnormality of the tricuspid apparatus 

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• 
Functional Tricuspid Regurgitation 
Global or regional right ventricular wall motion abnormalities causing leaflet 
restriction or tethering with or without dilatation of the tricuspid annulus, but with no 
significant abnormalities of the tricuspid leaflets 
• 
Lead-Induced Tricuspid Regurgitation 
ICD or pacemaker trans-tricuspid lead directly interfering with leaflet coaptation. 
 
GAMMA-GT/GAMMA-GLUTAMYL TRANSFERASE (GGT) 
GGT is an enzyme that is found in many organs throughout the body, with the highest 
concentrations found in the liver. GGT is elevated in the blood in most diseases that cause 
damage to the liver. 
 
GASTROINTESTINAL COMPLICATIONS 
Complications as a result of the TriClipTM procedure affecting the gastrointestinal tract requiring 
surgery.  May include fecal impaction, bowel obstruction, etc. 
 
HOSPITALIZATION (ALL-CAUSE) 
Defined as admission to inpatient unit or ward in the hospital for at least 24 hours, including 
emergency department stay.  Excludes hospitalizations planned for pre-existing conditions, 
unless there is worsening in the baseline condition.  
 
HEART FAILURE (HF) HOSPITALIZATION 
Defined as an event that meets the following criteria:  
1) Hospitalization (≥ 24 hours) with the primary reason for admission as acute 
decompensated HF and administration of intravenous or mechanical heart failure 
therapies, especially IV administration of diuretic therapy  
2) An unscheduled or unplanned admission to the emergency department, hospital 
outpatient observation unit, or hospital inpatient unit, and IV administration of diuretic 
therapy.  
3) Subject arrives in emergency department with clinical presentation meeting the 
criteria of heart failure, but dies in the emergency department before hospital admission. 
Overnight stays at nursing home facilities, physical rehab or extended care facilities, 
including hospice, will be included in the definition of hospitalization if related to a heart 
failure event. Elective heart failure “tune-ups” that occur following the TriClipTM procedure 
and prolong the Index hospitalization will not count as a heart failure hospitalization. 
OTHER CARDIOVASCULAR HOSPITALIZATION 

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Defined as treatment in any inpatient unit or ward in the hospital for at least 24 hours, 
including emergency department stay for conditions such as coronary artery disease, 
acute myocardial infarction, hypertension, cardiac arrhythmias, cardiomegaly, pericardial 
effusion, atherosclerosis and peripheral vascular disease, not related to heart failure as 
defined. 
NON-CARDIOVASCULAR HOSPITALIZATION 
Hospitalizations that are not heart failure or other cardiovascular hospitalizations, as 
defined above, will be categorized as non-cardiovascular hospitalizations. 
 
LIVER FAILURE 
New onset liver failure is defined as elevated alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) greater than 15 times the ULN. 
 
MAJOR ADVERSE EVENT (MAE) 
MAE is a composite of cardiovascular mortality, new onset renal failure, endocarditis requiring 
surgery, and non-elective cardiovascular surgery for TriClipTM device related adverse events 
occurring after the index procedure 
 
 
 
 
 
MAJOR BLEEDING  
Major bleeding is defined as bleeding ≥ Type 3 based on a modified Bleeding Academic 
Research Consortium (BARC) 1 definition: 
• 
Type 3  
o 
Type 3a  
 
Overt bleeding plus hemoglobin drop of 3 to <5 g/dL* (provided  
hemoglobin drop is related to bleed)  
 
Any transfusion with overt bleeding 
o 
Type 3b  
 
Overt bleeding plus hemoglobin drop ≥5 g/dL* (provided hemoglobin drop 
is related to bleed)  
 
Cardiac tamponade 
 
1 Mehrana R, Rao SV, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus 
report from the Bleeding Academic Research Consortium. Circulation 2011;123:2736-2747. 

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 
Bleeding requiring surgical intervention for control (excluding 
dental/nasal/skin/hemorrhoid) 
 
Bleeding requiring intravenous vasoactive agents 
o 
Type 3c  
 
Intracranial hemorrhage (does not include microbleeds or hemorrhagic 
transformation, does include intraspinal) 
 
Subcategories confirmed by autopsy or imaging or lumbar puncture 
 
Intraocular bleed compromising vision 
• 
Type 4: CV Surgery-related bleeding  
o 
Perioperative intracranial bleeding within 48 h 
o 
Reoperation after closure of sternotomy for the purpose of controlling bleeding 
o 
Transfusion of ≥5 U whole blood or packed red blood cells within a 48-h period† 
o 
Chest tube output ≥2L within a 24-h period 
• 
Type 5: Fatal bleeding  
o 
Type 5a  
 
Probable fatal bleeding; no autopsy or imaging confirmation but clinically 
suspicious 
o 
Type 5b  
 
Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation  
*Corrected for transfusion (1 U packed red blood cells or 1 U whole blood=1 g/dL hemoglobin) 
†Cell saver products are not counted 
 
MAJOR VASCULAR COMPLICATION 
Any major complication, relating to, or affecting, the circulatory system as a result of the 
TriClipTM procedure, including new onset of any of the following:   
• 
Hematoma at access site >6 cm.; 
• 
Retroperitoneal hematoma; 
• 
Arterio-venous fistula; 
• 
Symptomatic peripheral ischemia/ nerve injury with clinical signs or symptoms lasting >24 
hours;  
• 
Vascular surgical repair at catheter access sites;  
• 
Pulmonary embolism; 
• 
Ipsilateral deep vein thrombus; or 
• 
Access site-related infection requiring intravenous antibiotics and/or extended 
hospitalization. 
 
MELD SCORE 
The Model for End-Stage Liver Disease, or MELD, is a scoring system for assessing the 
severity of chronic liver disease. The following parameters are used to determine MELD score: 
Creatinine level, Bilirubin level, INR (international normalized ratio), and serum sodium level. 
The score is calculated as follows: 
Candidates who are at least 12 years old receive an initial MELD(i) score equal to:  
0.957 x Loge(creatinine mg/dL) + 0. 378 x Loge(bilirubin mg/dL) + 1.120 x Loge (INR) + 0.643 
Laboratory values less than 1.0 will be set to 1.0 when calculating a candidate’s MELD score. 

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The following candidates will receive a creatinine value of 4.0 mg/dL:  
• Candidates with a creatinine value greater than 4.0 mg/dL 
• Candidates who received two or more dialysis treatments within the prior 7 days 
• Candidates who received 24 hours of continuous veno-venous hemodialysis (CVVHD) within 
the prior 7 days  
The maximum MELD score is 40. The MELD score derived from this calculation will be rounded 
to the tenth decimal place and then multiplied by 10.  
For candidates with an initial MELD score greater than 11, the MELD score is then re-calculated 
as follows: MELD = MELD(i) + 1.32*(137-Na) – [0.033*MELD(i)*(137-Na)] Sodium values less 
than 125 mmol/L will be set to 125, and values greater than 137 mmol/L will be set to 137. 
MODIFIED RANKIN SCALE SCORE DESCRIPTIONS 
0. No symptoms at all 
1. No significant disability despite symptoms; able to carry out all usual duties and activities 
2. Slight disability; unable to carry out all previous activities, but able to look after own affairs 
without assistance 
3. Moderate disability; requiring some help, but able to walk without assistance 
4. Moderately severe disability; unable to walk without assistance and unable to attend to own 
bodily needs without assistance 
5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention 
6. Dead 
 
MYOCARDIAL INFARCTION 
Myocardial infarction (MI) classification and criteria for diagnosis is defined as follows:  
Peri-procedural MI (≤ 72 hours after TriClipTM procedure) 
Mandatory: CK-MB (preferred) ≥10x ULN within 72 hrs. post- TriClipTM procedure in 
patient with normal baseline CK-MB  
OR 
Mandatory: CK-MB ≥5x ULN within 72 hrs. post- TriClipTM procedure in patient with 
normal baseline CK-MB plus new pathological Q-waves in ≥2 contiguous leads, or new 
LBBB  
 
Post-surgery 
Mandatory: CK-MB ≥10x ULN (preferred) within 24 hrs. of cardiothoracic surgery plus 1 
of the following: 
• 
New pathological Q-waves in ≥2 contiguous leads or new persistent LBBB on ECG 
≥30 min. and ≤72 hrs. post-CABG cardiothoracic surgery, or 
 

TRILUMINATE Pivotal CIP 
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• 
New substantial wall motion abnormalities by imaging except new septal or apical 
abnormalities. 
 
Spontaneous MI (>72 hours after TriClipTM procedure)  
Any one of the following criteria: 
• 
Detection of rise and/or fall of cardiac biomarkers (CK-MB) with at least one 
value above the upper limits of normal (ULN), together with evidence of 
myocardial ischemia with at least one of the following:  
 
o ECG changes indicative of new ischemia [new ST-T changes or new left 
bundle branch block (LBBB)] 
o New pathological Q waves in at least two contiguous leads 
o Imaging evidence of new loss of viable myocardium or new wall motion 
abnormality 
 
• 
Sudden, unexpected cardiac death, involving cardiac arrest, often with symptoms 
suggestive of myocardial ischemia, and accompanied by presumably new ST 
elevation, or new LBBB, and/or evidence of fresh thrombus by coronary 
angiography and/or at autopsy, but death occurring before blood samples could 
be obtained, or at a time before the appearance of cardiac biomarkers in the 
blood. 
 
• 
Pathological findings of an acute myocardial infarction. 
 
NEW YORK HEART ASSOCIATION CLASSIFICATION (NYHA CLASS) 
 
Class I 
Patients with cardiac disease but without resulting limitations of physical 
activity. 
Class II 
Patients with cardiac disease resulting in slight limitation of physical activity.  
Patients are comfortable at rest.  Ordinary physical activity results in fatigue, 
palpitation, dyspnea, or anginal pain. 
Class III 
Patients with cardiac disease resulting in marked limitation of physical activity.  
Patients are comfortable at rest.  Less than ordinary physical activity causes 
fatigue, palpitation dyspnea, or anginal pain. 
Class IV 
Patients with cardiac disease resulting in inability to carry on any physical 
activity without discomfort.  Symptoms of cardiac insufficiency or of the 
anginal syndrome may be present even at rest.  If any physical activity is 
undertaken, discomfort is increased. 
 

TRILUMINATE Pivotal CIP 
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NON-ELECTIVE (i.e., URGENT or EMERGENT) CARDIOVASCULAR SURGERY FOR 
DEVICE RELATED EVENTS 
Cardiovascular surgical procedure performed for device related complication requiring surgery 
within 24 hours of onset of adverse event, including events found during scheduled follow-up.  If 
non-urgent surgery was performed within 24 hours of the onset of the adverse event but was 
not required within this timeframe, it will not be considered “non-elective”.   Examples of Device 
Related Complications that may lead to non-elective cardiovascular surgery include, myocardial 
perforation, Single Leaflet Device Attachment (confirmed by Echo Core Lab), embolization of 
the TriClipTM or TriClipTM System components, iatrogenic atrial septal defect, or the need for 
tricuspid valve replacement instead of repair due at least in part to the TriClipTM procedure or 
the presence of the TriClipTM. 
 
OPTIMAL MEDICAL THERAPY OR OPTIMAL THERAPY  
For Tricuspid Regurgitation:  Currently per ESC 2012 guidelines, the only medical therapy 
described is, “Diuretics reduce congestion. Specific therapy of the underlying disease is 
warranted.”  Subjects should be on stable dose of diuretics for 30 days before the screening 
assessments (such as TTE/TEE). Stable dose is defined as no more than a 100% increase or a 
50% decrease in dose. 
For Mitral Regurgitation: Subjects with current or prior symptoms of heart failure and reduced 
LVEF should be on stable optimally uptitrated medical therapy recommended according to 
current guidelines (J Am Coll Cardiol. 2013 Jun 5. doi:pii: S0735-1097(13)02114-1.) as standard 
of care for heart failure therapy in the United States. This minimally includes an ACE-inhibitor 
(ACE-I) at stable doses for 30 days prior to subject enrollment in the trial, if tolerated, and a beta 
blocker (carvedilol, sustained release metoprolol succinate, or bisoprolol) for 90 days prior to 
subject enrollment in the trial, if tolerated, with a stable up-titrated dose for 30 days prior to 
subject enrollment in the trial. This also includes an Angiotensin II Receptor Blocker (ARB) at 
stable doses for 30 days prior to subject enrollment in the trial, if tolerated, when ACE-I is not 
tolerated. Stable is defined as no more than a 100% increase or a 50% decrease in dose. 
If the subject is intolerant to ACE-I, ARB, or beta blockers, documented evidence must be 
available. In those intolerant to both ACE-I and ARB, combination therapy with hydralazine and 
oral nitrate should be considered. Therapeutic equivalence for ACE-I substitutions is allowed 
within the trial enrollment stability timelines. Aldosterone receptor antagonists [or 
mineralocorticoid receptor antagonists] are recommended in patients with NYHA class II-IV 
heart failure and who have LVEF of 35% or less, unless contraindicated, to reduce morbidity 
and mortality. Patients with NYHA class II should have a history of prior cardiovascular 
hospitalization or elevated plasma natriuretic peptide levels to be considered for aldosterone 
receptor antagonists. If aldosterone inhibitor therapy is to be administered, it must be initiated 
and optimized at least 30 days prior to trial enrollment. Stability criteria are the same as for other 
neurohormonal antagonists. Eplerenone requires dosage stability for 30 days prior to subject 
enrollment in the trial similar to the other agents. Diuretics may be used as necessary to keep 
the subject euvolemic. All heart failure therapeutics and dosages should be documented in the 
electronic case report forms.  

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It is recognized that approximately two-thirds of patients with HF have underlying CAD 
(ischemic cardiomyopathy). Therefore, it is imperative that appropriate treatment for CAD be 
used, according to the ACC/AHA Guidelines for Heart Failure. Specific recommendations listed 
in those guidelines are listed as follows: 
• 
Use of nitrates and beta blockers for the treatment of angina, 
• 
Coronary revascularization according to recommended guidelines in patients who have 
both HF and angina, 
• 
Patients with coronary artery disease and HF should be treated in accordance with 
recommended guidelines for chronic stable angina, 
• 
Use of antiplatelet agents for prevention of MI and death in patients with HF who have 
underlying coronary artery disease 
In addition, revascularization (i.e., percutaneous coronary intervention, etc.) should occur prior 
to subject enrollment in the trial as applicable. 
 
PERIPHERAL EDEMA 
Accumulation of fluid causing swelling in tissues perfused by the peripheral vascular system, 
usually in the lower limbs 
 
RENAL FAILURE 
For this trial, new onset renal failure is defined as new need for dialysis or a creatinine 
increasing to 3.5 mg/dL or greater 
Note: Increase of creatinine less 1.0 mg/dL over baseline is NOT considered renal failure 
 
SINGLE LEAFLET DEVICE ATTACHMENT (SLDA) 
Defined as unilateral TriClipTM detachment from one leaflet as assessed by the study site and 
confirmed by the ECL.  Reasons for TriClipTM Detachment include leaflet tearing, TriClipTM 
unlocking, TriClipTM fracture or inadequate TriClipTM placement.  Not included are any fractures 
or other failures of the TriClipTM that do not result in TriClipTM detachment from one or both 
leaflets.   
 
STROKE/CEREBROVASCULAR ACCIDENT and TIA 
Cerebrovascular Accident (Stroke) is defined as an acute episode of focal or global neurological 
dysfunction caused by brain, spinal cord, or retinal vascular injury as a result of hemorrhage or 
infarction.  Stroke may be classified as ischemic or hemorrhagic with appropriate sub-definitions 
or as undetermined if there is insufficient information to allow categorization as ischemic or 
hemorrhagic. 

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An entity closely related to ischemic stroke is transient ischemic attack (TIA).  TIA is defined as 
a transient episode of focal neurological dysfunction caused by brain, spinal cord, or retinal 
ischemia, without acute infarction.  The difference between TIA and ischemic stroke is the 
presence of infarction.  In the absence of affirmative evidence confirming the presence or 
absence of infarction, a symptom duration of 24 hours will be used to distinguish TIA from 
ischemic stroke.  By definition, TIA does not produce lasting disability. 
The assessment of disability resulting from the stroke will be performed by the modified Rankin 
Scale (mRS).  Assessment of the mRS is only required at scheduled visits through 24 months 
after onset of stroke, if stroke occurred.  This approach will maximize the detection of new 
strokes, assist in ongoing evaluation of events previously determined to be TIAs, and provide an 
accepted and reliable indicator of the long-term impact of a given stroke.  A disabling stroke is 
one that results (at 90 days after stroke onset) in an mRS score of 2 or more and in an increase 
of at least one mRS category from the individual’s pre-stroke baseline.  A non-disabling stroke is 
one that results (at 90 days after stroke onset) in an mRS score of less than 2 or that does not 
result in an increase of at least one mRS category from an individual’s pre-stroke baseline. 
Although imaging (typically, MRI for acute and chronic ischemia and haemorrhage, and CT for 
acute and chronic haemorrhage and chronic ischemia) is often used to supplement the clinical 
diagnosis of stroke, a diagnosis of stroke may be made on clinical grounds alone.   
 
Diagnostic criteria 
Acute episode of a focal or global neurological deficit with at least one of the following: 
change in level of consciousness, hemiplegia, hemiparesis, numbness or sensory loss 
affecting one side of the body, dysphasia or aphasia, hemianopia, amaurosis fugax, or 
other neurological signs or symptoms consistent with stroke 
Stroke – Duration of a focal or global neurological deficit ≥24 h; OR <24 h if available 
neuroimaging documents a new hemorrhage or infarct; OR the neurological deficit 
results in death 
TIA – Duration of a focal or global neurological deficit <24 h, any variable neuroimaging 
does not demonstrate a new hemorrhage or infarct 
No other readily identifiable non-stroke cause for the clinical presentation (e.g. brain 
tumor, trauma, infection, hypoglycemia, peripheral lesion, pharmacological influences), 
to be determined by or in conjunction with designated neurologist* 
Confirmation of the diagnosis by at least one of the following: 
– Neurologist or neurosurgical specialist 
– Neuroimaging procedure (CT scan or brain MRI), but stroke may be diagnosed on 
clinical grounds alone 

TRILUMINATE Pivotal CIP 
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Stroke classification 
Ischemic – An acute episode of focal cerebral, spinal, or retinal dysfunction caused by 
infarction of central nervous system tissue. 
Hemorrhagic – An acute episode of focal or global cerebral or spinal dysfunction caused 
by intraparenchymal, intraventricular, or subarachnoid hemorrhage. 
Undetermined – An acute episode where there is insufficient information to allow 
categorization as ischemic or hemorrhagic. 
Stroke definitions† 
Disabling stroke –  a mRS score of 2 or more at 90 days and an increase of at least one 
mRS category from an individual’s pre-stroke baseline 
Non-disabling stroke – a mRS score of less than 2 at 90 days or one that does not result 
in an increase of at least one mRS category from an individual’s pre-stroke baseline 
*Patients with non-focal global encephalopathy will not be reported as a stroke without 
unequivocal evidence of cerebral infarction based upon neuroimaging studies (CT scan 
or Brain MRI). 
†Modified Rankin Scale assessments should be made by qualified individuals according 
to a certification process. 
 
SYMPTOMATIC TRICUSPID REGURGITATION 
Symptomatic refers to limitation of physical activity (i.e. NYHA Classification II, III or IV) 
 
TRICUSPID VALVE STENOSIS 
Defined as a tricuspid valve orifice of ≤ 1.0 cm2 and/or mean gradient ≥5 mmHg as measured by 
the Echocardiography Core Laboratory. Other parameters (PHT ≥ 190 msec or CW TV VTI >60 
cm) may also suggest significant tricuspid stenosis. 
 
TRICUSPID REGURGITATION SEVERITY 
TR grading will be based on a 5-point scale: mild (1), moderate (2), severe (3, 4, 5).  Mild, 
moderate, and severe will be graded based on the 2017 ASE Guidelines (Zoghbi 2017).  
Further stratification of severe into 3, 4 and 5 have been developed by the Echo Scientific 
Committee to provide further granularity in the range beyond severe.   See Appendix XII for 
further grading information.  
 
 
 

TRILUMINATE Pivotal CIP 
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Study Name: TRILUMINATE Pivotal 
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 Page 97 of 136 
20 APPENDIX IV: REFERENCES 
1. American College ofCardiology/American Heart Association Task Force on Practice 
Guidelines. 2014 AHA/ACC guideline for the management of patients with valvular heart 
disease: a report of the American College of Cardiology/American Heart Association Task F. 
Nishimura, RA, et al. 22, Jun 10, 2014, J Am Coll Cardiol, Vol. 63, pp. e57-e185. 
2. Impact of tricuspid regurgitation on long-term survival. Nath, J, Foster, E and Heidenreich, 
PA. 3, Feb 4, 2004, J Am Coll Cardiol., Vol. 43, pp. 405-409. 
3. Management of tricuspid valve regurgitation. Antunes, MJ and JB., Barlow. 2, Feb 2007, 
Heart, Vol. 93, pp. 271-276. 
4. The tricuspid valve: current perspective and evolving management of tricuspid regurgitation. 
Rogers JH, Bolling SF. 20, May 26, 2009, Circulation, Vol. 119, pp. 2718-2725. 
5. Conservative management of tricuspid regurgitation in patients undergoing mitral valve 
replacement. Braunwald NS, Ross J, Morrow AG. 1967, Circulation, Vol. 4 Suppl, pp. I63-I69. 
6. Management of tricuspid regurgitation. De Bonis, M, et al. 6, Jul 2014, F1000Prime Rep., 
Vol. 8, p. 58. 
7. Outcomes With Transcatheter Mitral Valve Repair in the United States: An STS/ACC TVT 
Registry Report. Sorajja P, Vemulapalli S, Feldman T, Mack M, Holmes DR Jr, Stebbins A, 
Kar S, Thourani V, Ailawadi G. 19, Nov 7, 2017, J Am Coll Cardiol, Vol. 70, pp. 2315-2327. 
8. Impact of tricuspid regurgitation on survival in patients with chronic heart failure: unexpected 
findings of a long-term observational study. Neuhold S, Huelsmann M, Pernicka E, Graf A, 
Bonderman D, Adlbrecht C, Binder T, Maurer G, Pacher R, Mascherbauer J. 11, Mar 2013, 
Eur Heart J., Vol. 34, pp. 844-852. 
9. Association of tricuspid regurgitation with clinical and echocardiographic outcomes after 
percutaneous mitral valve repair with the MitraClip System: 30-day and 12-month follow-up from 
the GRASP Registry. Ohno Y, Attizzani GF, Capodanno D, Cannata S, Dipasqua F, Immé S, 
Barbanti M, Ministeri M, Caggegi A, Pistritto AM, Chiarandà M, Ronsivalle G, Giaquinta S, 
Farruggio S, Mangiafico S, Scandura S, Tamburino C, Capranzano P, Grasso C. 11, Nov 
2014, Eur Heart J Cardiovasc Imaging., Vol. 15, pp. 1246-1255. 
10. 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of 
Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American 
Heart Association Task Force on Clinical Practice Guidelines. Nishimura, RA, et al. 2, Jul 11, 
2017, J Am Coll Cardiol. , Vol. 70, pp. 252-289. 
11. Tricuspid valve repair: durability and risk factors for failure. McCarthy, PM, et al. 3, Mar 
2004, Thorac Cardiovasc Surg., Vol. 127, pp. 674-685. 
12. Reoperations after tricuspid valve repair. Bernal, JM, et al. 2, Aug 2005, J Thorac 
Cardiovasc Surg. , Vol. 130, pp. 498-503. 

TRILUMINATE Pivotal CIP 
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 Page 98 of 136 
13. 2017 ESC/EACTS Guidelines for the management of valvular heart. Baumgartner H, Falk 
V, Bax JJ, De Bonis M, Hamm C, Holm PJ, Iung B,. 36, Sep 21, 2017, Eur Heart J., Vol. 38, 
pp. 2739-2791. 
14. Predictors of secondary tricuspid regurgitation after left-sided valve replacement. . Wang G, 
Sun Z, Xia J, Deng Y, Chen J, Su G, Ke Y. 9, 2008, Surg Today., Vol. 38, pp. 778-783. 
15. Transcatheter treatment of severe tricuspid regurgitation using the MitraClip system. 
Presentation at TCT 2016 Conference. Jorg Hausleiter, et al. s.l. : TCT, October 31, 2016. 
16. Transcatheter Treatment of Severe Tricuspid Regurgitation with the Edge-to-Edge: MitraClip 
Technique. . Nickenig G, et al.,. s.l. : Circulation. , 2017 Mar 23. 
 
 
 

TRILUMINATE Pivotal CIP 
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Study Name: TRILUMINATE Pivotal 
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 Page 102 of 136 
References-  
1. 
Rogers JH, Bolling SF. The Tricuspid Valve: Current perspective and evolving management 
of tricuspid regurgitation. Circulation (May) 2009; 119 (20): 2718-2725 
2. 
Zhu TY, Min XP, Zhang HB, Meng X. Preoperative risk factors for residual tricuspid 
regurgitation after isolated left-sided valve surgery, Cardiology 2014; 129(4): 242–249 
3. 
Nickenig G, et al. Transcatheter Treatment of Severe Tricuspid Regurgitation with the 
Edgeto‐Edge MitraClip Technique. Circulation 2017; 135(19):1802‐1814 
4. 
Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O'Gara PT, 
Ruiz CE, Skubas NJ, Sorajja P., Sundt TM 3rd, Thomas JD. 2014 AHA/ACC Guideline for 
the Management of Patients with Valvular Heart Disease. Circulation (Jun) 2014; 129 (23): 
2440-2492 
5. 
Matsunaga A, Duran CMG. Progression of tricuspid regurgitation after repaired functional 
ischemic mitral regurgitation. Circulation 2005; 112 [suppl I]: I-453–I-457 
6. 
Filsoufi F, Anyanwu AC, Salzberg SP, Frankel T, Cohn LH, Adams DH. Long-term outcomes 
of tricuspid valve replacement in the current era. Ann Thorac Surg (Sep) 2005; 80 (3): 845–
850 
  
  
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
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 Page 103 of 136 
22 APPENDIX VI: LABELS  
 
 
  
 

TRILUMINATE Pivotal CIP 
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Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 104 of 136 
23 APPENDIX VII: CASE REPORT FORMS  
 
  
  
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 105 of 136 
24 APPENDIX VIII: INFORMED CONSENT FORM  
 
  
  
  
  
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 111 of 136 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is a quality record which will be retained per 
the local retention policy.  
 
 Page 117 of 136 
 
28 APPENDIX XII:  ECHOCARDIOGRAPHY TR GRADING 
 
 
 
  
 
   
 
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is a quality record which will be retained per 
the local retention policy.  
 
 Page 118 of 136 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 119 of 136 
 
29 APPENDIX XIII: SIX MINUTE WALK TEST GUIDELINES – AMERICAN 
THORACIC SOCIETY 
 
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 120 of 136 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 123 of 136 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 129 of 136 
• 
The study will not be submitted for review to the Competent Authority, only standard 
vigilance reporting will be observed. Local and/or regional requirements might be still 
applicable and will be tracked in a study specific Safety Plan. 
• 
Financial disclosures will not be collected from the Investigators. 
• 
separate study risk assessment will not be applied, the applicable risks are described 
and communicated in the current Clinical Investigational Plan and IFUs for the medical 
devices under investigation 
 
 
 

TRILUMINATE Pivotal CIP 
(Version F) 
Study Document No: ABT-CIP-10249 
Study Name: TRILUMINATE Pivotal 
CONFIDENTIAL: May not be reproduced outside of Abbott without written permission from Document Control. This is 
a quality record which will be retained per the local retention policy.  
 
 Page 134 of 136 
32.6 Schedule of Events  
a If performed within 14 days of assessment for screening, then screening can be used for baseline.