Early Feasibility Study of the Edwards FORMA Tricuspid Transcatheter Repair System
Phase: NA
Conditions: Tricuspid Valve Regurgitation
Sponsor: Edwards Lifesciences

Edwards FORMA Tricuspid Transcatheter Repair System Early Feasibility Study 
 
 
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Early Feasibility Study of the Edwards  
FORMA Tricuspid Transcatheter Repair System 
 
 
CLINICAL PROTOCOL 
(Clinical Investigational Plan) 
 
 
Study Number:  2014-04 
Version:  M 
Effective Date:   February 4, 2019 
 
 
CONFIDENTIAL 
 
Study Sponsor: 
 
 
 
 
 
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TABLE OF CONTENTS 
SYNOPSIS ................................................................................................................................................. 5 
1 
INTRODUCTION ............................................................................................................................ 10 
1.1 
CLINICAL BACKGROUND ...................................................................................................................... 10 
1.1.1 
Disease Process ..................................................................................................................... 10 
1.1.2 
Etiology .................................................................................................................................. 10 
1.2 
ALTERNATIVE TREATMENT/THERAPIES ................................................................................................... 12 
1.2.1 
Surgical Tricuspid Valve Intervention .................................................................................... 12 
1.2.2 
Medical Therapy .................................................................................................................... 13 
1.2.3 
Percutaneous Tricuspid Valve Repair .................................................................................... 13 
1.2.4 
Transcatheter Tricuspid Valve Replacement ......................................................................... 13 
2 
STUDY PURPOSE ........................................................................................................................... 14 
2.1 
INTENDED USE .................................................................................................................................. 14 
2.2 
PRIOR TESTING ................................................................................................................................. 14 
2.3 
CLINICAL EXPERIENCE ......................................................................................................................... 14 
2.4 
STUDY DEVICE .................................................................................................................................. 19 
2.4.1 
General Device Description and Components ....................................................................... 19 
2.4.2 
Edwards FORMA Tricuspid Transcatheter Spacer System ..................................................... 19 
2.4.3 
Access Sheaths ...................................................................................................................... 22 
2.4.4 
Edwards FORMA Tricuspid Transcatheter Railing Delivery System ....................................... 24 
2.4.5 
Edwards FORMA Tricuspid Transcatheter Retrieval System ................................................. 25 
3 
RISK ANALYSIS .............................................................................................................................. 25 
3.1 
POTENTIAL RISKS ............................................................................................................................... 25 
3.2 
RISK MANAGEMENT .......................................................................................................................... 28 
3.3 
BENEFITS ......................................................................................................................................... 28 
3.4 
JUSTIFICATION .................................................................................................................................. 29 
4 
STUDY OBJECTIVES ....................................................................................................................... 29 
5 
STUDY ENDPOINTS........................................................................................................................ 29 
5.1 
FEASIBILITY ENDPOINTS ...................................................................................................................... 29 
5.1.1 
Safety Endpoint ..................................................................................................................... 29 
5.1.2 
Performance Endpoint ........................................................................................................... 29 
5.1.3 
Other Endpoints..................................................................................................................... 30 
6 
STUDY DESIGN .............................................................................................................................. 30 
7 
PATIENT POPULATION .................................................................................................................. 31 
7.1 
DEMOGRAPHIC AND CLINICAL CHARACTERISTICS...................................................................................... 31 
7.2 
INCLUSION CRITERIA .......................................................................................................................... 31 
7.3 
EXCLUSION CRITERIA .......................................................................................................................... 31 
8 
PROCEDURES AND METHODS ....................................................................................................... 33 
8.1 
INFORMED CONSENT .......................................................................................................................... 33 
8.2 
PATIENT ENROLLMENT ....................................................................................................................... 34 
8.3 
BASELINE EVALUATION ....................................................................................................................... 34 
8.4 
ANTIPLATELET / ANTICOAGULATION THERAPY ......................................................................................... 37 
8.5 
DEVICE PREPARATION ........................................................................................................................ 38 
8.6 
IMPLANT PROCEDURE ........................................................................................................................ 38 
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8.6.1 
Antibiotic Prophylaxis ............................................................................................................ 40 
8.6.2 
Contrast Media ...................................................................................................................... 40 
8.6.3 
Day 1 Post-Implant ................................................................................................................ 40 
8.6.4 
Discharge ............................................................................................................................... 40 
8.7 
FOLLOW UP VISITS ............................................................................................................................ 42 
8.7.1 
Visit & Assessment Windows................................................................................................. 43 
8.8 
MISSED PATIENT VISITS ...................................................................................................................... 48 
8.9 
WITHDRAWAL CRITERIA AND PROCEDURES ............................................................................................ 48 
8.10 
PATIENT STUDY COMPLETION .............................................................................................................. 49 
9 
TRAINING ...................................................................................................................................... 49 
9.1 
INVESTIGATORS DEVICE TRAINING ........................................................................................................ 49 
9.2 
TRAINING OF INVESTIGATIONAL SITE PERSONNEL ..................................................................................... 49 
9.3 
TRAINING DOCUMENTATION ............................................................................................................... 50 
10 
INVESTIGATIONAL DEVICE MANAGEMENT ................................................................................... 50 
10.1 
DEVICE SHIPMENTS ............................................................................................................................ 50 
10.2 
DEVICE ACCOUNTABILITY .................................................................................................................... 50 
10.3 
DEVICE STORAGE ............................................................................................................................... 50 
10.4 
DEVICE RETURN ................................................................................................................................ 51 
11 
DATA COLLECTION AND REPORTING ............................................................................................. 51 
11.1 
DATA COLLECTION METHODS .............................................................................................................. 51 
11.2 
CASE REPORT FORMS ......................................................................................................................... 51 
11.3 
SOURCE DOCUMENTATION REQUIREMENTS ............................................................................................ 52 
11.4 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES ...................................................................... 52 
12 
REPORTABLE EVENTS / EFFECTS .................................................................................................... 53 
12.1 
DEFINITIONS ..................................................................................................................................... 53 
12.1.1 Adverse Event ........................................................................................................................ 53 
12.1.2 Adverse Device Effect ............................................................................................................ 53 
12.1.3 Serious Adverse Event ........................................................................................................... 53 
12.1.4 Serious Adverse Device Effect ................................................................................................ 54 
12.1.5 Unanticipated Serious Adverse Device Effect ........................................................................ 54 
12.1.6 Device Deficiency and Malfunction ....................................................................................... 54 
12.2 
REPORTING PROCEDURE ..................................................................................................................... 54 
12.3 
FINDINGS EXPECTED TO OCCUR WITH TREATMENT OF TRICUSPID REGURGITATION AND/OR INTERVENTIONAL CARDIAC 
PROCEDURES THAT DO NOT REQUIRE REPORTING TO THE SPONSOR ......................................................................... 57 
12.4 
DEATHS AND EXPLANTS ...................................................................................................................... 58 
12.4.1 Patient Deaths ....................................................................................................................... 58 
12.4.2 Device Explants ...................................................................................................................... 58 
13 
STATISTICAL ANALYSIS .................................................................................................................. 59 
13.1 
SAMPLE SIZE .................................................................................................................................... 59 
13.2 
ANALYSIS POPULATION ....................................................................................................................... 59 
13.3 
DEVICE SUCCESS ENDPOINT ANALYSIS ................................................................................................... 59 
13.4 
PROCEDURE SUCCESS ENDPOINT ANALYSIS ............................................................................................. 60 
13.5 
CLINICAL SUCCESS ENDPOINT ANALYSIS............................................................................................... 60 
13.6 
ADDITIONAL SAFETY ANALYSIS ............................................................................................................. 60 
13.7 
MISSING DATA ................................................................................................................................. 60 
13.8 
ANALYSIS SOFTWARE ......................................................................................................................... 60 
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14 
MONITORING ............................................................................................................................... 61 
14.1 
MONITORING METHODS .................................................................................................................... 61 
14.2 
MONITORING PLAN ........................................................................................................................... 61 
14.3 
PROTOCOL DEVIATION ....................................................................................................................... 62 
14.4 
COMMUNICATION PROCEDURES ........................................................................................................... 63 
15 
DATA MONITORING COMMITTEE ................................................................................................. 63 
16 
APPLICABLE REGULATIONS AND GUIDELINES ............................................................................... 63 
16.1 
DATA PROTECTION AND PATIENT CONFIDENTIALITY ................................................................................. 64 
16.2 
INVESTIGATOR RESPONSIBILITIES .......................................................................................................... 64 
16.2.1 General Duties ....................................................................................................................... 64 
16.2.2 Investigator Records .............................................................................................................. 64 
16.2.3 Investigator Reports .............................................................................................................. 65 
16.3 
SPONSOR RESPONSIBILITIES ................................................................................................................. 65 
16.3.1 General Duties ....................................................................................................................... 65 
16.4 
SELECTION OF INVESTIGATORS ............................................................................................................. 65 
16.4.1 Monitoring the Study ............................................................................................................ 66 
16.4.2 Sponsor Records .................................................................................................................... 66 
16.4.3 Sponsor Reports .................................................................................................................... 66 
16.5 
STUDY CHANGES ............................................................................................................................... 67 
16.6 
STUDY COMPLETION OR TERMINATION AND CLOSE-OUT .......................................................................... 67 
16.7 
AUDITS AND INSPECTIONS ................................................................................................................... 67 
16.8 
PUBLICATION POLICY ......................................................................................................................... 67 
17 
REFERENCES .................................................................................................................................. 68 
18 
DEFINITIONS ................................................................................................................................. 69 
19 
APPENDIX A - SAMPLE INFORMED CONSENT FORM ..................................................................... 90 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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SYNOPSIS 
 
Study Number: 
2014-04  
Title: 
Early Feasibility Study of the Edwards FORMA Tricuspid Transcatheter 
Repair System 
Study Sponsor 
Contacts:  
 
 
  
 
 
Study Principal 
Investigator: 
 
  
Study 
Objective: 
The objectives of this early feasibility study are to: 
• 
Evaluate the safety and function of the Edwards FORMA Tricuspid 
Transcatheter Repair System 
• 
Provide guidance for future clinical study designs utilizing the 
Edwards FORMA Tricuspid Transcatheter Repair System 
• 
Provide guidance for future Edwards FORMA Tricuspid 
Transcatheter Repair System development efforts 
Study Devices: 
The Edwards FORMA Tricuspid Transcatheter Repair System: 
• 
Edwards FORMA Tricuspid Transcatheter Spacer System, Model 
9900SSA  
• 
Edwards FORMA Tricuspid Transcatheter Guide Sheath, Model 
9900GSA 
• 
Edwards FORMA Tricuspid Transcatheter Introducer Sheath, Model 
9900IS 
• 
Edwards FORMA Tricuspid Transcatheter Railing Delivery System, 
Model 9900DSA  
• 
Edwards FORMA Tricuspid Transcatheter Retrieval System, Model 
9900RSA 
Intended Use: 
The Edwards FORMA Tricuspid Transcatheter Repair System is intended 
for patients with tricuspid regurgitation who are deemed to be 
candidates for transcatheter tricuspid valve repair with the Edwards 
FORMA Tricuspid Transcatheter Repair System by the local Heart Team 
(a minimum of one cardiologist and one cardiac surgeon).  
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Study Design: 
This is a multi-site, prospective, early feasibility study. 60 patients will be 
enrolled in the study.  All enrolled study patients will be assessed for 
clinical follow-up at the following intervals:  1 month, 6 months, 1 year 
and annually for 3 years post implant procedure. 
Study Population: 
Adult patients with clinically significant, symptomatic, functional, 
tricuspid regurgitation who are deemed to be candidates for 
transcatheter tricuspid valve repair by the local Heart Team (a minimum 
of one cardiologist and one cardiac surgeon). 
Enrollment Criteria 
(Inclusion): 
 
1.  Age ≥ 18 years old 
2. Symptomatic severe (Stage D) functional, tricuspid regurgitation 
(per applicable guidelines) 
3. Symptomatic despite medical therapy; patient must be on diuretic 
therapy. 
4. The local site Heart Team determines that the patient is 
appropriate for transcatheter tricuspid repair  
5. Patient is willing and able to comply with all specified study 
evaluations and provides written informed consent. 
 
Enrollment Criteria 
(Exclusion): 
1. Echocardiographic/CT parameters (any of the following): 
a. Vessel access or right heart anatomy precluding proper 
device introduction, deployment and function 
b. LVEF < 30% 
c. Severe right ventricular dysfunction as assessed by the 
core lab 
d. Patients with systolic pulmonary artery pressure > 60 
mmHg 
2. Primary tricuspid disease (e.g. rheumatic, myxomatous 
degeneration, tricuspid valve prolapse, tricuspid stenosis)  
3. Previous tricuspid leaflet repair or tricuspid valve replacement 
4. Presence of two or more trans-tricuspid leads or any single 
trans-tricuspid lead: 
a. Precluding proper placement of or interferes with 
device 
b. Implanted within the last 180 days 
c. With pacemaker dependency 
5. Severe aortic, mitral and/or pulmonic valve stenosis and/or 
regurgitation  
6. Active endocarditis within 90 days of the scheduled implant 
7. Significant pericardial effusion 
8. Intra-cardiac mass, thrombus, or vegetation 
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9. Untreated clinically significant coronary artery disease 
requiring revascularization 
10. Recurrent (>2 per 12 months) hospitalizations or ER visit for 
COPD exacerbation 
11. MI or known unstable angina within 30 days prior to the index 
procedure 
12. Any therapeutic invasive cardiac procedure within 30 days prior 
to the index procedure, or any dual anti-platelet therapy 
(DAPT) requirement which cannot be interrupted for 7 days  
13. Any cardiac surgery, within 3 months prior to procedure 
14. Hemodynamic instability or on IV inotropes within 30 days of 
the scheduled implant 
15. Severe uncontrolled hypertension (SBP ≥ 180 mmHg and/or 
DBP ≥ 110 mm Hg) 
16. Cerebrovascular Accident (CVA) or TIA within the past 30 days 
17. Kidney dysfunction with estimated Glomerular Filtration Rate 
(eGFR) < 30 ml/min/1.73 m2 or patient is on chronic dialysis 
18. Any physical impairment which limits the patient’s capacity to 
complete functional testing due to other medical conditions 
independent of their TR  (e.g. orthopedic condition) 
19. Significant frailty (i.e. Katz Index of Independence in Activities 
of Daily Living (ADL) ≤ 2) within 90 days of scheduled implant 
procedure 
20. Continuous home oxygen for primary severe COPD  
21. Chronic anemia (Hgb < 9 g/dL) not corrected by transfusion 
22. Thrombocytopenia (Platelet count< 100,000/mm3) or 
thrombocytosis (Platelet count > 750,000/mm3) 
23. Bleeding disorders or hypercoagulable state 
24. Active peptic ulcer or active gastrointestinal (GI) bleeding 
within 90 days of the scheduled implant 
25. Cardiac cachexia 
26. Contraindication to anticoagulants or antiplatelet agents 
27. Currently or history of IV drug use 
28. Pregnant or lactating; or female of childbearing potential with a 
positive pregnancy test 24 hours before any study-related 
radiation exposure 
29. Patients in whom transesophageal echocardiography is 
contraindicated 
30. Known allergy to cobalt chromium, nitinol, titanium or contrast 
agents that cannot be adequately pre-medicated. 
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31. Known hypersensitivity or contraindication to procedural 
medications which cannot be adequately managed medically 
32. Impaired judgment and/or is undergoing emergent or urgent 
treatment for tricuspid insufficiency 
33. Currently participating in another investigational drug or device 
study that has not completed the primary endpoint or that 
clinically interferes with the endpoints of this study 
34. Co-morbid condition(s) that, in the opinion of the Investigator, 
limit life expectancy to < 12 months 
35. Co-morbid condition(s) that, in the opinion of the investigator, 
could limit the patient’s ability to participate in the study, 
including compliance with follow-up requirements, or that 
could impact the scientific integrity of the study 
36. Patient is under guardianship 
 
Feasibility 
Endpoints: 
Safety:  
Composite of major adverse events (MAE) defined as cardiovascular 
mortality, myocardial infarction, new need for renal replacement 
therapy, severe bleeding, re-intervention and major access site and 
vascular complications at 30 days. 
 
Performance:  
• 
Device success: device is deployed as intended and the delivery 
system is successfully retrieved as intended at the time of the 
patient’s exit from the cardiac catheterization laboratory.  
 
• 
Procedural success: device success with evidence of tricuspid 
regurgitation (TR) reduction as evidenced by a relative reduction in 
EROA of ≥ 30% from baseline to discharge and without the need for 
a surgical or percutaneous intervention prior to hospital discharge.  
 
• 
Clinical success: procedural success without MAEs at 30 days.  
(MAEs: cardiovascular mortality, myocardial infarction, new need 
for renal replacement therapy, severe bleeding, re-intervention 
and major access site and vascular complications) 
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Study Committees: 
Independent Data Monitoring Committee (DMC)  
 
The DMC will consist of a minimum of 3 members, all members being 
physicians; one cardiothoracic surgeon, one interventional cardiologist 
and one cardiologist 
Echocardiography 
Core Laboratory: 
  
  
  
 
 
 
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1 INTRODUCTION 
1.1 
CLINICAL BACKGROUND 
1.1.1 DISEASE PROCESS 
Tricuspid Regurgitation (TR), tricuspid insufficiency or tricuspid incompetence describes a 
condition in which blood flow through the tricuspid valve flows in the incorrect direction 
during part of the cardiac cycle. Normally, during diastole, the tricuspid valve opens as a 
result of atrial pressure from the right atrium, allowing blood to flow through the tricuspid 
valve, into the right ventricle.  Diastole ends with atrial contraction and the tricuspid valve 
closing to prevent a reversal of blood flow.  However, in patients with TR, the tricuspid 
valve is unable to form a tight seal at diastole end (when it should be closed), allowing 
blood to flow back into the right atrium.  
 
Although TR often accompanies mitral or aortic valve disease, it is usually asymptomatic, 
traditionally considered less clinically significant, and left untreated.  This scenario where 
the tricuspid valve is left untreated has resulted in the tricuspid valve being commonly 
referred to as the “forgotten” valve.  While trace to mild levels of TR are commonly found 
in a large number of patients without clinical consequence, moderate and severe levels 
can have detrimental effects on a patients quality of life [1]. Patients with severe TR 
usually present with signs or symptoms of right heart failure (HF), including peripheral 
edema and ascites[2].  
1.1.2 ETIOLOGY 
TR can have many underlying etiologies, but the majority of these can be divided into two 
major categories: degenerative and functional TR.  Degenerative (primary, organic or 
structural) TR refers to regurgitation resulting from disease processes affecting the 
integrity of the tricuspid valve leaflets and/or valve apparatus, such as in rheumatic heart 
disease, tricuspid valve prolapse or endocarditis.  In contrast, functional (secondary or 
non-structural) TR refers to regurgitation occurring in the absence of significant structural 
disease of the tricuspid valve and/or apparatus.  Functional TR occurs in approximately 
80% of cases of significant TR[2], resulting from annular dilation and right ventricular 
enlargement, which is often secondary to left heart failure from myocardial or valvular 
causes, right ventricular volume and pressure overload, and dilation of cardiac chambers. 
Significant TR may be clinically silent for a prolonged period, during which time 
progressive right ventricle (RV) dilatation and dysfunction may develop, similar to 
changes that can occur with asymptomatic mitral regurgitation (MR) and its effect on LV 
function. 
 
 
 
 
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Figure 1: Dilation of the Tricuspid Annulus – Dreyfus et al.[3] 
 
 
Tricuspid regurgitation is a common echocardiographic finding that is often considered 
benign unless associated with significant pulmonary hypertension or RV or LV 
dysfunction. It has been shown that increasing TR severity is associated with worse 
survival regardless of left ventricular ejection fraction (LVEF) or pulmonary artery 
pressure[1]. Severe TR is associated with a poor prognosis, independent of age, 
biventricular systolic function, RV size, and IVC dilation[1]. 
 
Figure 2: Kaplan-Meier survival curves for all patients with tricuspid regurgitation 
(TR).[1] 
 
 
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1.2 
ALTERNATIVE TREATMENT/THERAPIES 
1.2.1 SURGICAL TRICUSPID VALVE INTERVENTION 
The decision as to treat TR has been controversial over the years, but has recently become 
recommended in symptomatic patients and in some cases asymptomatic patients as 
prophylactic treatment at the time of MR surgery[4]. The decision as to whether repair or 
replacement is recommended is demonstrated in the diagram below. 
 
Figure 3: 2014 AHA/ACC Indications for Tricuspid Surgery[2] 
 
 
 
Several techniques are available to correct functional tricuspid regurgitation. These 
include the stitch annuloplasty, such as semicircular (classical De Vega repair) or simple 
lateral annuloplasty (Kay), novel techniques such as edge-to-edge or clover technique and 
suture bicuspidization technique, use of flexible and rigid prosthetic rings or 3D rings, 
flexible prosthetic bands, and use of artificial chordae with polytetrafluoroethylene 
sutures for anterior and septal tricuspid leaflet pathology. Whereas the short-term 
outcomes of these techniques are satisfactory, the majority are limited in the mid- and 
long term by unacceptably high rates of residual and/or recurrent regurgitation[5]. 
  
While repair, specifically annuloplasty is considered the procedure of choice, if repair is 
not feasible or unsuccessful, replacement may be considered[6]. For replacement both 
bioprosthetic as well as mechanical valves provide viable options. 
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1.2.2 MEDICAL THERAPY 
TR patients may be managed with diuretics for symptoms and only considered for surgery 
after advanced RV dysfunction, liver dysfunction or cirrhosis have developed. 
Additionally, medical therapies may be used to reduce elevated pulmonary artery 
pressures and/or pulmonary resistance[2].  
For the patient population that would benefit from surgical intervention, but is 
characterized as high-risk or non-surgical, medical management is likely to only provide 
temporary symptom relief. The lack of benefit from medical therapies has prompted the 
search for alternative repair or replacement therapies.   
1.2.3 PERCUTANEOUS TRICUSPID VALVE REPAIR 
Percutaneous tricuspid valve repair therapies have considerable interest due to the 
minimally invasive nature of the procedures, particularly since surgery in functional 
patients is only indicated when they are undergoing concomitant valve surgery[2, 7].   
 
Percutaneous devices are being investigated which mimic surgical repair techniques. 
These devices are targeted for patients who are at high operative risk for surgery. These 
devices aim to approximate the leaflets by anchoring in the annulus and pulling the 
anterior leaflet towards the posterior leaflet, simulating a bicuspidization. Another 
emerging technology is a device which uses pledgets in the annulus to reduce the size of 
the annulus.  Edwards is also currently exploring annular reconstruction devices and edge 
to edge repair techniques.  However all of the devices mentioned are in the 
investigational phase and are not commercially available. 
1.2.4 TRANSCATHETER TRICUSPID VALVE REPLACEMENT 
Transcatheter valve replacement with the Edwards Sapien or Medtronic Melody valve has 
been described in the published literature on only single case studies or limited 
retrospective clinical series but primarily for valve-in-valve patients or patients with 
rheumatic disease.  This is not the patient population that the Edwards FORMA Tricuspid 
Transcatheter Repair system is intended for as the Edwards device is intended for 
functional tricuspid regurgitation. 
 
Percutaneous devices are being investigated for tricuspid valve replacement.  
Additionally, percutaneous bicaval valve implantation has been used to treat tricuspid 
regurgitation by placing a valve in both the inferior vena cava and the superior vena cava. 
While this does not directly correct the TR, it prevents back flow beyond the right atrium 
with the goal of reducing symptoms, normalizing liver function, and improving physical 
capacity. 
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2 STUDY PURPOSE 
The early feasibility study of the Edwards FORMA Tricuspid Transcatheter Repair System 
is a multi-site, prospective, early feasibility study to evaluate the safety and function of 
the Edwards FORMA Tricuspid Transcatheter Repair System. 
 
Data collected in this clinical study will include safety and function of the investigational 
system as well as up to 3 year clinical outcomes. 
2.1 
INTENDED USE 
The Edwards FORMA Tricuspid Transcatheter Repair System is intended for treatment of 
patients with tricuspid regurgitation who are deemed to be candidates for transcatheter 
tricuspid valve repair with the Edwards FORMA Tricuspid Transcatheter Repair System by 
a local team comprised of a minimum of one Cardiologist, and one Cardiac Surgeon 
(herein after referred to as the local Heart Team). 
2.2 
PRIOR TESTING 
A Report of Priors (Clinical Investigator’s Brochure (CIB)) has been prepared for the 
Edwards FORMA Tricuspid Transcatheter Repair System.  This document provides the 
prior testing conducted on the system components. 
2.3 
CLINICAL EXPERIENCE 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
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Total 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                 
 
 
 
 
 
 
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Fina

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2.4 
STUDY DEVICE 
2.4.1 
GENERAL DEVICE DESCRIPTION AND COMPONENTS 
The Edwards FORMA Tricuspid Transcatheter Repair System (herein after referred to as 
the FORMA System) is comprised of five (5) different sub-systems as listed below (Table 
5).   A general device description will be provided for all components of the Edwards 
FORMA System.  Further detailed information such as materials, manufacturing, testing, 
etc. however, will be provided in the Report of Priors (Clinical Investigator’s Brochure 
(CIB)).   
 
The following table includes the device names and model numbers of the components 
that make up the FORMA System: 
 
Table 5 – Device Names and Model Numbers 
 
Product Name 
Models 
Edwards FORMA Tricuspid Transcatheter Spacer System 
 
Edwards FORMA Tricuspid Transcatheter Guide Sheath 
 
Edwards FORMA Tricuspid Transcatheter Introducer Sheath  
 
Edwards FORMA Tricuspid Transcatheter Railing Delivery System 
  
Edwards FORMA Tricuspid Transcatheter Retrieval System 
   
2.4.2 
EDWARDS FORMA TRICUSPID TRANSCATHETER SPACER SYSTEM 
 
 
 
 
.   
2.4.2.1 Spacer Device  
 
 
 
 
 
 
 
 
 
 
 
  
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Fi

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Figure 11: Edwards FORMA Tricuspid Transcatheter Guide Sheath, Model 9900GSA 
 
  
 
 
 
 
 
 
 
 
 
 

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Edwards FORMA Tricuspid Transcatheter Repair System Early Feasibility Study 
 
 
   
 
 
 
  
 
  
 
 
 
 
 
 
 
   
 
 
 
3 RISK ANALYSIS 
A risk analysis has been conducted, in accordance with ISO 14971:2012 “Application of 
risk management to medical devices”. The risks associated with this investigational device 
have been identified by performing Failure Mode and Effect Analysis (FMEA)/Risk 
Analysis. Risks have been proven minimized through appropriate design control, 
confirmed by bench testing, pre-clinical animal testing and clinical surveillance presented 
in the Clinical Investigator’s Brochure.  
 
During the conduct of the clinical study, the existing risk control measures shall be 
reviewed to identify if other hazards have been introduced.  If any new hazards were 
introduced by any risk control measures, the associated risk(s) shall be re-assessed and 
addressed.  
3.1 
POTENTIAL RISKS 
The potential risks of use of the FORMA System are similar to those encountered with 
standard cardiac catheterization and use of anesthesia and have been listed in two 
categories below. First, there are the potential complications associated with the overall 
procedure including standard cardiac catheterization and the use of anesthesia. Second, 
there are the additional potential risks associated with the use of the FORMA System.  
Estimated occurrence rankings of the potential risks are provided in the Sample Informed 
Consent Form in Appendix A.  
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Risks related to the overall procedure including standard cardiac catheterization and the 
use of anesthesia may include, but may not be limited to, the following:  
 
• abnormal lab values; 
• access site AV fistula or pseudoaneurysm; 
• allergic reaction to anesthesia or to contrast media; 
• anemia; 
• angina; 
• arrhythmia; 
• bleeding; 
• cardiovascular or vascular injury including perforation, obstruction, or dissection 
of valvular structures that may require intervention, including access sites; 
• conduction system injury (defect) which may require replacement or 
implantation of a pacemaker (permanent or temporary); 
• death; 
• dyspnea (e.g., orthopnea); 
• electrolyte imbalance; 
• embolization including air, particulate, calcific material, or thrombus; 
• exercise intolerance or weakness; 
• fever; 
• heart failure; 
• heart murmur; 
• hematoma; 
• hemorrhage requiring transfusion or intervention; 
• hypertension/hypotension; 
• infection, including septicemia and endocarditis; 
• inflammation; 
• leaflet damage; 
• myocardial infarction; 
• pain or changes at the access site; 
• paralysis; 
• pericardial effusion/cardiac tamponade; 
• permanent disability; 
• pleural effusion; 
• pulmonary edema; 
• renal failure; 
• renal insufficiency; 
• reoperation; 
• restenosis; 
• retroperitoneal bleed; 
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• skin burn; 
• syncope; 
• systemic peripheral ischemia/nerve injury; 
• thromboembolic events, stroke, transient ischemic attack, clusters, or 
neurological changes; 
• wound dehiscence, delayed or incomplete healing. 
 
In addition to the risks listed above, additional potential risks associated with the use of 
the FORMA System may include, but may not be limited to, the following: 
 
• cardiac arrest; 
• cardiac dysrhythmias requiring replacement or implantation of a pacemaker 
(temporary or permanent); 
• cardiac failure/low cardiac output; 
• cardiogenic shock; 
• chordal damage, rupture; 
• damage to or interference with function of pacemaker or implantable 
cardioverter-defibrillator (ICD); 
• deterioration of native valve (leaflet tear/tearing, leaflet retraction, leaflet 
thickening, leaflet stenosis, or other); 
• device degeneration;  
• device explants;  
• device migration, malposition or embolization requiring intervention;  
• device thrombosis requiring intervention;  
• emergency cardiac surgery;  
• hemolysis;  
• leakage around device; 
• non-emergent reoperation;  
• nonstructural implant dysfunction;  
• papillary muscle damage; 
• pneumothorax; 
• pulmonary artery outflow tract obstruction;  
• structural deterioration (wear, fracture, calcification, shaft creep, or other);  
• thromboembolism (permanent or transient pulmonary and/or neurological 
events); 
• transvalvular flow disturbances; 
• valvular regurgitation; 
• ventricular or atrial wall damage, abrasion, or perforation; 
• worsening of heart failure; 
• worsening of valvular insufficiency. 
 
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There may be other risks that are unknown at this time. All safety events will be collected 
and reviewed throughout the entire study and follow-up period. The Investigators will be 
notified of any additional risks identified that could affect the health, safety or welfare of 
the study patients. 
3.2 
RISK MANAGEMENT 
All efforts will be made to minimize the identified risks by selecting Investigators, team 
members and study sites who meet the following criteria: 
 
• Interventional Cardiologist - must be board certified (or equivalent), experienced with 
performing transcatheter heart valve repair and replacement, and skilled in 
percutaneous coronary interventions and structural heart interventions. 
• Access Management Physician - must be board certified (or equivalent), experienced 
with access management (subclavian/axillary vein access) and right heart 
interventions.  
There will be strong interdepartmental collaboration between interventional cardiology 
and cardiovascular surgery operators and a designated team of nurses, technicians and 
colleagues from supporting medical disciplines (e.g., anesthesiologist, heart failure 
specialist, echo-cardiographer, radiologist).  
 
The procedural location is to be an operating room, catheterization lab or hybrid 
operating room with fluoroscopic and echocardiographic imaging capabilities. 
 
Adverse events will be reviewed by the Study Sponsor, Data Safety Monitoring Board and 
Clinical Events Committee as defined in the respective charters.   
3.3 
BENEFITS 
The clinical benefits of using the FORMA System for the treatment of tricuspid 
regurgitation are not known at the present time.  There are no guaranteed benefits from 
participation in this clinical study and being treated with the investigational FORMA 
System. 
 
Tricuspid valve repair with the FORMA System may result in one or more of the following 
benefits for patients typically considered high risk for tricuspid repair or replacement: 
decrease in tricuspid regurgitation, acute alleviation of symptoms related to tricuspid 
insufficiency, and/or improved morbidity and mortality.  
Information gained from the conduct of this study may be of benefit to other people with 
the same medical condition in the future as the indication for the system is expanded.  
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3.4 
JUSTIFICATION  
This study, the first with the FORMA System, is designed as a multi-site, prospective, early 
feasibility study. This study is designed to confirm that the safety and function observed 
in non-clinical testing is also observed in a limited human population. 
 
The treatments currently available for this patient population include palliative medical 
therapy and high-risk surgical replacement or repair of the tricuspid valve.    Treatment 
with the FORMA System may enable patients with tricuspid regurgitation to undergo 
tricuspid valve repair via a minimally invasive approach.   
4 STUDY OBJECTIVES 
The objectives of this early feasibility study are to: 
 
• Evaluate the safety and function of the FORMA System 
• Provide guidance for future clinical study designs utilizing the FORMA System 
• Provide guidance for future FORMA System development efforts 
5 STUDY ENDPOINTS 
5.1 
FEASIBILITY ENDPOINTS  
5.1.1 SAFETY ENDPOINT 
Composite of major adverse events (MAE) defined as cardiovascular mortality, 
myocardial infarction, new need for renal replacement therapy, severe bleeding, re-
intervention and major access site and vascular complications at 30 days. 
5.1.2 PERFORMANCE ENDPOINT 
5.1.2.1 Device Success  
Device is deployed as intended and the delivery system is successfully retrieved as 
intended at the time of the patient’s exit from the cardiac catheterization laboratory. 
5.1.2.2 Procedural Success  
Device success with evidence of TR reduction as evidenced by a relative reduction in EROA 
of ≥ 30% from baseline to discharge and without the need for a surgical or percutaneous 
intervention prior to hospital discharge. 
5.1.2.3 Clinical Success  
Procedural success without MAEs at 30 days.  (MAEs: cardiovascular mortality, myocardial 
infarction, new need for renal replacement therapy, severe bleeding, re-intervention and 
major access site and vascular complications) 
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5.1.3 OTHER ENDPOINTS 
5.1.3.1 
Echocardiographic parameters 
A. Reduction in TR severity (assessed by TR grade and quantitative measures) as assessed by 
TEE pre- and post-implant  in the procedure room.  
Additional echocardiographic parameters will be compared to baseline: 
B. TTE parameters assessed at baseline, discharge, 30 days, 6 months, 1 year and 
annually until 3 years post procedure. 
1. 
TR grade- qualitative assessment 
2. 
Vena Contracta (2D) 
3. 
EROA (PISA/2D or 3D/3D color doppler) 
4. 
Regurgitant volume  
5. 
Tricuspid annular diameter (end-diastolic – S-L) 
6. 
Tricuspid annular area (2D/3D mid-diastolic) 
7. 
Tenting area and distance 
8. 
Forward stroke volume 
9. 
RV dimensions 
10. Right atria volume 
11. Left ventricular Ejection Fraction 
12. Inferior Vena Cava dimensions/respiratory variations 
13. Hepatic vein flow reversal 
14. Pulmonary artery pressure (peak) 
15. Right ventricular function 
 
6 STUDY DESIGN 
This is a multi-site, prospective, early feasibility study designed to evaluate the safety and 
function of the FORMA System. 
 
A total of sixty patients will be enrolled in the study.  All enrolled study patients will be 
assessed for clinical follow-up at the following intervals:  1 month, 6 months, 1 year and 
annually for 3 years post implant procedure. 
 
A description of each study visit and required study procedures is included in Section 8.0, 
Procedures and Methods.  In addition, a summary of required procedures is listed in Table 
13.  
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7 PATIENT POPULATION 
7.1 
DEMOGRAPHIC AND CLINICAL CHARACTERISTICS 
This clinical study is for adult patients with clinically significant, symptomatic, functional, 
tricuspid regurgitation who are deemed to be candidates for transcatheter tricuspid valve 
repair by the local Heart Team.   
 
All patients who meet the initial study eligibility requirements will be evaluated for study 
participation. 
 
Candidates for this study must meet all of the following inclusion criteria and none of the 
exclusion criteria: 
7.2 
INCLUSION CRITERIA  
The Investigator has the responsibility of screening potential patients to determine if the 
patients meet all the inclusion criteria.  The following are requirements for entry into the 
study:  
 
1.  Age ≥ 18 years old 
2. Symptomatic severe (Stage D) functional, tricuspid regurgitation (per applicable 
guidelines) 
3. Symptomatic despite medical therapy; patient must be on diuretic therapy. 
4. The local site Heart Team determines that the patient is appropriate for 
transcatheter tricuspid repair  
5. Patient is willing and able to comply with all specified study evaluations and 
provides written informed consent. 
7.3 
EXCLUSION CRITERIA 
The Investigator at the study site must exclude patients if any of the exclusion criteria are 
present. The following are the criteria for exclusion from participating in the clinical study: 
 
1. Echocardiographic/CT parameters (any of the following): 
a. Vessel access or right heart anatomy precluding proper device 
introduction, deployment and function 
b. LVEF < 30% 
c. Severe right ventricular dysfunction as assessed by the core lab 
d. Patients with systolic pulmonary artery pressure > 60 mmHg 
2. Primary tricuspid disease (e.g. rheumatic, myxomatous degeneration, tricuspid 
valve prolapse, tricuspid stenosis)  
3. Previous tricuspid leaflet repair or tricuspid valve replacement 
4. Presence of two or more trans-tricuspid leads or any single trans-tricuspid lead: 
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a. Precluding proper placement of or interferes with device 
b. Implanted within the last 180 days 
c. With pacemaker dependency 
5. Severe aortic, mitral and/or pulmonic valve stenosis and/or regurgitation  
6. Active endocarditis within 90 days of the scheduled implant 
7. Significant pericardial effusion 
8. Intra-cardiac mass, thrombus, or vegetation 
9. Untreated clinically significant coronary artery disease requiring revascularization 
10. Recurrent (>2 per 12 months) hospitalizations or ER visit for COPD exacerbation 
11. MI or known unstable angina within  30 days prior to the index procedure 
12. Any therapeutic invasive cardiac procedure within 30 days prior to the index 
procedure, or any dual anti-platelet therapy (DAPT) requirement which cannot be 
interrupted for 7 days  
13. Any cardiac surgery, within 3 months prior to procedure 
14. Hemodynamic instability or on IV inotropes within 30 days of the scheduled 
implant 
15. Severe uncontrolled hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mm Hg) 
16. Cerebrovascular Accident (CVA) or TIA within the past 30 days 
17. Kidney dysfunction with estimated Glomerular Filtration Rate (eGFR) < 30 
ml/min/1.73 m2 or patient is on chronic dialysis 
18. Any physical impairment which limits the patient’s capacity to complete functional 
testing due to other medical conditions independent of their TR  (e.g. orthopedic 
condition) 
19. Significant frailty (i.e. Katz Index of Independence in Activities of Daily Living (ADL) 
≤ 2) within 90 days of scheduled implant procedure 
20. Continuous home oxygen for primary severe COPD  
21. Chronic anemia (Hgb < 9 g/dL) not corrected by transfusion 
22. Thrombocytopenia (Platelet count< 100,000/mm3) or thrombocytosis (Platelet 
count > 750,000/mm3) 
23. Bleeding disorders or hypercoagulable state 
24. Active peptic ulcer or active gastrointestinal (GI) bleeding within 90 days of the 
scheduled implant 
25. Cardiac cachexia 
26. Contraindication to anticoagulants or antiplatelet agents 
27. Currently or history of IV drug use 
28. Pregnant or lactating; or female of childbearing potential with a positive 
pregnancy test 24 hours before any study-related radiation exposure 
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29. Patients in whom transesophageal echocardiography is contraindicated 
30. Known allergy to cobalt chromium, nitinol, titanium or contrast agents that cannot 
be adequately pre-medicated. 
31. Known hypersensitivity or contraindication to procedural medications which 
cannot be adequately managed medically 
32. Impaired judgment and/or is undergoing emergent or urgent treatment for 
tricuspid insufficiency 
33. Currently participating in another investigational drug or device study that has not 
completed the primary endpoint or that clinically interferes with the endpoints of 
this study 
34. Co-morbid condition(s) that, in the opinion of the Investigator, limit life 
expectancy to < 12 months 
35. Co-morbid condition(s) that, in the opinion of the investigator, could limit the 
patient’s ability to participate in the study, including compliance with follow-up 
requirements, or that could impact the scientific integrity of the study 
36. Patient is under guardianship 
8 PROCEDURES AND METHODS 
8.1 
INFORMED CONSENT  
As the study Sponsor, Edwards Lifesciences must approve any modifications to the 
Informed Consent Form prior to submission to the institutional review board (IRB), and/or 
FDA (as required).  A sample Informed Consent Form is provided in Appendix A – Sample 
Informed Consent Form.   
Once the patient’s physician has determined the patient’s eligibility for the study, the 
background of the proposed study, and the benefits and risks of the procedures and study 
should be explained to the patient.  The patient (or the patient’s legal representative) 
must sign the institution’s approved Informed Consent Form prior to participation.  
Failure to provide informed consent renders the patient ineligible for the study. 
The consent form will be written in the native language of the patient and administered 
only by the Investigator or IRB approved personnel who speak the native language of the 
patient.  The Principal Investigator or delegated person administering the consent must 
sign and date the Informed Consent Form to indicate that the purpose, risks and benefits 
of the study were explained to the patient and that their signature was witnessed. 
The Investigator will retain the original consent form, a copy will be filed in the patient’s 
medical record, and a copy of the Informed Consent Form will be provided to the patient. 
Informed consent MUST be obtained prior to any study related procedures.   Signed 
informed consent forms must be retained by the study site for verification during on-site 
monitoring visits.  
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8.2 
PATIENT ENROLLMENT  
All patients enrolled under this Revision L of the Clinical Protocol will be consented, 
treated and followed according to the requirements described herein.  Patients enrolled 
under previous versions of the Clinical Protocol will not be required to reconsent under 
Revision L and will be followed according to the requirements of the protocol version to 
which they were consented.   
A Screening/Enrollment Log, provided by the Sponsor, will be maintained at the study site 
to document the screening and enrollment of all patients assessed for study participation.  
The screening of patients qualifying for this study should be carried out in a sequential, 
prospective manner, such that all patients are offered the possibility of participating in 
the study, and are therefore evaluated according to the selection criteria defined in this 
protocol.  Patients who are consented to participate in the study but do not fulfill 
enrollment criteria, will be considered “screen failures” and will not count towards the 
overall enrollment cap.  The reason for “screen failure” will be recorded on the screen 
failure log.  Reasons for screen failure may include but are not limited to: 
• Qualifying patient is not offered an opportunity to participate by Investigator  
• Qualifying patient refuses to participate 
• Investigator opts for alternative therapy for qualifying patient   
• Potential patient fails the screening criteria  
All patients assessed for study participation that have signed the informed consent form 
will be entered on the screening log.  These patients will be assigned a sequential patient 
ID number by the study Sponsor.  The patient ID number together with the patient initials 
shall be used to identify the patient on all study-related documents. 
Patient will be considered “provisionally enrolled” when they have signed the informed 
consent form agreeing to participate in the study and have been deemed eligible for study 
participation by meeting the study criteria (Sections 7.2-7.3).  A patient will be considered 
“enrolled” at the time of skin incision to introduce the FORMA System into the body. 
8.3 
BASELINE EVALUATION  
1. Informed consent will be obtained from all patients who have been determined to 
be eligible study candidates and agreed to participate in the study.  
2. Patient demographics and medical history (includes 12 months prior 
hospitalizations including emergency department (ED) visits, paracentesis)  
3. Clinical Evaluation (includes vital signs, concomitant medical treatments, edema 
grading, ankle circumference measurements, weight and height) and NYHA 
classification  
4. Administration of Health Status Questionnaires (e.g., SF-12, KCCQ) 
5. Administration of Six Minute Walk Test  (6MWT) 
6. Administration of Katz Index of Independence in Activities of Daily Living (ADL) 
7. Administration of Canadian Study of Health and Aging (CSHA) Clinical Frailty Scale© 
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8. Administration of Patient Edema Questionnaire 
9. Administration of Patient Preference Survey  
10. Modified Rankin score (mRS) * 
11. Clinical Laboratory Tests 
a. The following lab tests shall be done within 30 days of the scheduled 
implant procedure: 
i. Troponins and cardiac enzymes (CK-MB) - MI within 30 days of the 
scheduled implant procedure is an exclusion from study 
participation 
b. The following lab tests shall be done ≤ 2 weeks before implant procedure: 
i. CBC  and platelet count  
ii. Complete metabolic panel  
iii. Liver panel including gamma-glutamyl transferase (GGT)  
iv. Serum Creatinine and eGFR  
c. The following lab tests shall be done ≤ 48 hours before the implant 
procedure: 
i. βHCG for women who are not sterile or post-menopausal- positive 
result is an exclusion from study participation. 
ii. INR and PTT/aPTT  
12. Standard 12-lead Electrocardiogram (ECG)  
13. Comprehensive Transthoracic Echocardiogram (TTE must be collected per 
Echocardiography Acquisition Protocol) 6.   
14. Transesophageal Echocardiogram (TEE), including but not limited to transgastric 
views. 
15. All candidates must have pre-implant procedure imaging (e. g., Computed 
Tomography (CT) Angiogram), that captures the anatomy of the subclavian and 
axillary 
veins, 
superior 
vena 
cava, 
tricuspid 
valve 
and 
sub-valvular 
structures/anatomy, right atrium and right ventricle.   
16. Invasive Hemodynamic Monitoring/Right Heart Catheterization that should include, 
but is not limited to, right atrial pressure (RAP), PAP, right ventricle pressure (RVP), 
cardiac output (CO), and PVR measurements.7  
17. Candidates with cardiac leads may also have a venogram (subclavian and axillary 
veins) as part of pre-implant procedure imaging, if venous patency cannot be 
determined by pre-procedure CT. 
18. Candidates with pacemaker leads must have interrogation of their device to 
determine pacing stability and pacing dependency.  Pacemaker dependency is 
defined as continuous ventricular stimulation without any pacemaker inhibition by 
                                                 
6 If candidate had new cardiac procedure since baseline TTE and TEE that were submitted for screening, 
the TTE and TEE should be repeated and resubmitted. 
7 If the screening echo confirms the PAP meets the study criteria, the right heart catheterization/ 
hemodynamic assessment at the baseline evaluation may be waived.   
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spontaneous cardiac activity determined during the last interrogation within 180 
days. 
19. Coronary angiogram 
*mRS will be conducted at baseline for all patients with a history of stroke.  For patients who 
experience a stroke during the study, mRS will be conducted closest to 90 days post event.   It is 
recognized that an assessment of stroke is incomplete without an appropriate measurement of 
the disability resulting from the stroke, hence, mRS closest to 90 days post event will be used to 
assess clinical disability. Every effort should be made to have a neurologist or neurology fellow 
perform the neurological assessments, or alternatively, a trained research team member certified 
in stroke assessment. mRS can be obtained by a certified research team member via phone 
interview with the patient or caregiver member if the patient is unable to visit the research office. 
 
Baseline data to be collected will include but is not limited to the information listed in the 
following table: 
Table 6 - Baseline Evaluation 
General Information 
Clinical Information 
Laboratory Measurements 
• Inclusion/exclusion 
evaluation 
• Informed consent 
• Age 
• Gender 
• Height 
• Weight 
 
• Local Heart Team 
determination 
• Patient demographics 
Medical history (e.g., 
EuroSCORE, STS Score) 
/prior cardiovascular 
interventions / surgeries / 
12-month prior 
hospitalizations and 
paracentesis 
• Vital signs (Blood pressure, 
heart rate) 
• Edema grading & ankle 
circumference 
measurements 
• Concomitant Medications 
and doses 
• NYHA classification 
• Echocardiographic 
measurements (TTE & TEE), 
tricuspid regurgitation & 
heart function  
•  CT 
• Coronary angiogram  
• Venogram (in patients with 
cardiac leads) if required 
Within 30 days of procedure: 
• Date of blood draw 
• Troponin1 and CK-MB1 
 
Within ≤ 2 weeks of 
procedure: 
• Date of blood draw 
• Serum Creatinine & eGFR 
• WBC 
• RBC 
• Hematocrit 
• Hemoglobin 
• Platelets 
• ALT/SGPT 
• AST/SGOT 
• Bilirubin  
• LDH 
• GGT 
• ALP 
• Albumin 
• Sodium & potassium 
• Urea  
Within ≤ 48 hours of 
procedure: 
• INR  & PTT/aPTT  
• βHCG, if applicable2 
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General Information 
Clinical Information 
Laboratory Measurements 
• Interrogation of pacemaker 
leads  
• Invasive Hemodynamic 
Monitoring/Right Heart 
Catheterization including 
pressure measurements  
• ECG results 
• Six minute walk test  
• Katz Index (ADL) test 
• CSHA Frailty scale 
• KCCQ & SF-12 
questionnaires 
• Edema Questionnaire 
• Preference Survey 
• mRS (if applicable) 
1. 
MI within 30 days of the scheduled implant procedure is an exclusion from study participation 
2. 
A positive result is an exclusion from study participation 
8.4 
ANTIPLATELET / ANTICOAGULATION THERAPY  
 
Recommendations for antiplatelet/anticoagulation therapy are detailed below and in 
Table 7.  Alternative anticoagulation/antiplatelet regimens may be considered according 
to the needs of individual patients or a hospital’s standard practice; these will not 
constitute a protocol deviation. For study patients on an existing dual antiplatelet therapy 
or with known hypersensitivity to the required medications, the investigator will 
determine the antiplatelet/anticoagulation therapy. 
 
Patients on anticoagulation (e.g. Warfarin or Apixaban) will discontinue use prior to 
implant procedure.  Patients not on anticoagulation prior to the procedure should receive 
Aspirin (at least 75 – 100 mg daily) and Plavix (300 mg or per investigator’s preference) 
prior to implant procedure.   
 
Heparin will be administered at procedure start, before introduction of any catheter into 
the vasculature.  During the procedure, ACT will be monitored and recorded on source 
documentation.  Heparin will be administered during the procedure as needed to 
maintain the patient’s ACT at ≥ 250 sec. The sheaths may be removed when ACT level is 
appropriate (e.g., reaches < 150 sec) after implantation of the study devices. 
 
Post procedure, patients on Aspirin and Plavix should continue receiving dual anti-platelet 
therapy through the 6 month follow up visit. The antiplatelet regimen past the 6-month 
follow-up visit will be determined at the Investigator’s discretion. 
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Patients on anticoagulation (e.g. Warfarin or Apixaban) will continue with their prescribed 
anticoagulation medications post implant procedure through the 6-month follow-up visit. 
 See Table 7. 
 
Table 7 – Summary of Recommended Concomitant Medical Therapy 
     *Anticoagulant: e.g., Warfarin or Apixaban 
 
8.5 
DEVICE PREPARATION  
A description of device preparation and use is provided in the IFUs, (See Report of 
Priors/Clinical Investigator’s Brochure). Investigators must be familiar with the 
information described in the IFU prior to use of the FORMA System.  
 
An Edwards Representative that has been trained on the preparation of the FORMA 
System will be in attendance at all implant procedures.  
 
 
8.6 
IMPLANT PROCEDURE  
The implant procedure shall be performed under general anesthesia with hemodynamic 
monitoring in an operating room, catheterization lab or hybrid operating room with 
fluoroscopic, angiographic and echocardiographic imaging capabilities.  The use of 
cardiopulmonary bypass is not required. 
 
The following study procedures will occur during the implant procedure: 
 
1. Safety Evaluation 
2. Transesophageal Echocardiogram  
3. Ventriculogram Imaging 
4. Invasive Hemodynamic Monitoring/Right Heart Catheterization including right 
atrial pressure measurements pre and post implant 
5. Heparin administration to achieve (and maintain) an ACT of ≥ 250 sec during the 
implant procedure 
 
Visit 
Patients on anticoagulant* prior 
to implant procedure 
Patients Not on anticoagulant* 
prior to implant procedure 
Pre Procedure 
Discontinue anticoagulant 
Start Aspirin and Plavix 
Intra-Procedure 
IV Heparin 
IV Heparin 
Post-Procedure 
through Month 6 
Resume anticoagulant 
Continue Aspirin and Plavix  
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Patients will be monitored in the operating room as needed with special attention to 
hemodynamic condition and cardiac rhythm. Subsequent monitoring of patients will be 
continued in the recovery room or ICU.  
 
The date of the implant procedure will be considered as Day 0 for the purpose of 
determining specified time intervals for the follow up visit for the implanted and non-
implanted cohorts. 
 
Procedure data to be collected will include but is not limited to the information listed in 
the following table: 
 
Table 8 – Procedure Information 
 
General Information 
Clinical Information 
Laboratory Measurements 
• Hospital admission date 
• Patient identification 
number 
• Names of 
Interventional 
Cardiologist & Access 
Management Physician 
• Procedure date 
• Access site 
• Timing of implant 
procedures 
• FORMA System 
identification & 
disposition 
• Fluoroscopy duration & 
contrast volume 
• Heparin administration 
& ACT levels 
• TEE measurements, 
tricuspid regurgitation & 
heart function  
• Ventriculogram Imaging 
• Invasive Hemodynamic 
Monitoring/Right Heart 
Catheterization and 
pressure measurements 
performed 
• Adverse events 
• Device malfunction  
Within 24 -48 hours post 
implant: 
• Troponin1 and  
CK-MB1 
• WBC 
• RBC 
• Hematocrit 
• Hemoglobin 
• Platelets 
• ALT/SGPT 
• AST/SGOT 
• Bilirubin 
• LDH 
• GGT 
• ALP 
• Albumin 
• Sodium & potassium 
• Urea 
• Serum creatinine & 
eGFR 
• PTT/aPTT & INR 
 
1. 
If an elevation was noted post implant (within 48 hours), tests must be repeated three times or 
until not clinically significant 
 
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8.6.1 ANTIBIOTIC PROPHYLAXIS  
It is recommended that all recipients be prophylactically treated for endocarditis to 
minimize the possibility of infection. 
8.6.2 CONTRAST MEDIA  
Careful management of contrast media is required for these patients. Accurate 
measurement of the dye used during the implant procedure shall be captured in the 
appropriate case report form.  
8.6.3 DAY 1 POST-IMPLANT 
The following study procedures will be performed 24-48 hours post implant procedure: 
 
1. Clinical Evaluation  
2. Safety Evaluation 
3. Clinical Laboratory Tests 
a. CBC and platelet count  
b. Complete metabolic panel  
c. Liver panel 
d. PTT/aPTT and INR  
e. Serum creatinine and eGFR 
f. Troponins and cardiac enzymes (CK-MB)  
4. Standard 12-lead ECG  
8.6.4 DISCHARGE 
The following procedures will be performed prior to discharge from the hospital/unit:  
 
1. Clinical Evaluation and Concomitant Medications  
2. Safety Evaluation 
3. Clinical Laboratory Tests 
a. CBC  and platelet count  
b. Complete metabolic panel  
c. Liver panel 
d. INR and PTT/aPTT  
e. Serum creatinine and eGFR  
f. Troponins and cardiac enzymes (CK-MB), only required if an elevation was 
noted post implant (within 48 hours) 
4. Standard 12-lead ECG 
5. Administration of Patient Edema Questionnaire 
6. Comprehensive Transthoracic Echocardiogram per echo core lab acquisition 
protocol 
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7. Modified Rankin score (mRS) mRS will be conducted for all patients who had a 
stroke since their last assessment. It is recognized that an assessment of stroke is 
incomplete without an appropriate measurement of the disability resulting from 
the stroke, hence, mRS closest to 90 days post event will be used to assess clinical 
disability. Every effort should be made to have a neurologist or neurology fellow 
perform the neurological assessments, or alternatively, a by a trained research 
team member certified in stroke assessment. mRS can be obtained by a certified 
research team member via phone interview with the patient or caregiver member 
if the patient is unable to visit the research office. 
 
Discharge data to be collected will include but is not limited to the information listed in 
the following table: 
Table 9 – Discharge Information 
 
General Information 
Clinical Information 
Laboratory Measurements 
• Discharge date & 
location 
discharged to 
(e.g., home) 
• Weight 
 
• Clinical evaluation 
(mobility, edema grading & 
ankle circumference 
measurements, ascites, 
access site) 
• Vital signs (Blood Pressure, 
Heart Rate) 
• TTE measurements, 
tricuspid regurgitation & 
heart function  
• ECG results 
• Concomitant medications 
and doses1 
• Edema Questionnaire 
• Adverse events 
• mRS (if applicable) 
 
• Date of blood draw 
• Troponin and CK-MB, if 
applicable 
• WBC 
• RBC 
• Hematocrit 
• Hemoglobin 
• Platelets 
• ALT/SGPT 
• AST/SGOT 
• Bilirubin 
• LDH 
• GGT 
• ALP 
• Albumin 
• Sodium & potassium 
• Urea 
• Serum creatinine & eGFR 
• INR & PTT/aPTT  
1. 
No changes in diuretics are allowed for at least 3 months post procedure unless patient presents 
with severe hypotension. 
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8.7 
FOLLOW UP VISITS 
Follow-up visits will be conducted at 1 month, 6 months, and annually for 3 years post 
implant procedure intervals as illustrated in Table 11. The following procedures will be 
conducted during follow up visits:  
 
1. Clinical Evaluation Hospitalizations and/or Clinic Visits and Paracentesis, 
Concomitant Medications and doses, Edema Grading, ankle circumference 
measurements, and NYHA classification 
2. Administration of Health Status Questionnaires (e.g., SF-12, KCCQ) 
3. Administration of Six Minute Walk Test 
4. Administration of Patient Edema Questionnaire 
5. Safety Evaluation  
6. Clinical Laboratory Tests : 
a. 
CBC  and platelet count  
b. 
Complete metabolic panel  
c. 
Liver panel 
d. 
INR and PTT/aPTT  
e. 
Serum creatinine and eGFR 
7. Standard 12-lead ECG 
8. Comprehensive Transthoracic Echocardiogram (TTE) per echo core lab acquisition 
protocol 
9. Modified Rankin Scale (mRS): mRS will be conducted for all patients who had a 
stroke since their last assessment. It is recognized that an assessment of stroke is 
incomplete without an appropriate measurement of the disability resulting from 
the stroke, hence, mRS closest to 90 days post event will be used to assess clinical 
disability. Every effort should be made to have a neurologist or neurology fellow 
perform the neurological assessments, or alternatively, a by a trained research 
team member certified in stroke assessment. mRS can be obtained by a certified 
research team member via phone interview with the patient or caregiver member 
if the patient is unable to visit the research office. 
  
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Follow-up data to be collected will include but is not limited to the information listed in 
the following table: 
 
Table 10 – Follow-Up Visit Information 
 
General Information 
Clinical Information 
Laboratory Measurements 
• Visit date 
• Height 
• Weight 
 
• Clinical evaluation 
(mobility, edema grading,  
ankle circumference 
measurements, 
ascites, access site) 
• Vital signs (Blood Pressure, 
Heart Rate) 
• Hospitalizations &/or clinic 
visits & paracentesis 
• NYHA classification 
• TTE measurements, 
tricuspid regurgitation & 
heart function  
• ECG results 
• Six minute walk test (pre & 
post walk data & results) 
• KCCQ & SF-12 
questionnaires 
• Edema Questionnaire 
• Concomitant Medications 
and doses1 
• Adverse events 
• mRS (if applicable) 
• Date of blood draw 
• WBC 
• RBC 
• Hematocrit 
• Hemoglobin 
• Platelets 
• ALT/SGPT 
• AST/SGOT 
• Bilirubin 
• LDH 
• GGT 
• ALP 
• Albumin 
• Sodium & potassium 
• Urea 
• Serum creatinine and eGFR 
• INR  & PTT/aPTT  
1. 
No changes in diuretics are allowed for at least 3 months post procedure unless patient presents 
with severe hypotension. 
8.7.1 VISIT & ASSESSMENT WINDOWS 
Post-procedure follow up visits will be performed on all implanted study patients at 1 
month, 6 months, and annually for 3 years post implant procedure intervals as illustrated 
in Table 11 below: 
 
 
 
 
 
 
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Table 11 – Follow-up Visit Windows 
 
Scheduled Follow-up Interval 
Follow-up Window 
1 month (30 days) 
± 7 days 
6 months (180 days) 
± 30 days 
Annually  (365 days) up to 3 years ± 45 days 
 
 
Table 12: Screening/Baseline Assessment Windows 
 
Assessment 
Window 
TTE* 
Within 60 days of submission to Sponsor 
TEE** 
Within 90 days of submission to Sponsor 
Hemodynamic Monitoring 
Within 90 days of scheduled implant procedure7 
Venogram (pacemaker 
lead patients)  
Within 90 days of scheduled implant procedure if venous 
patency cannot be determined by CT 
CT Angiogram** 
Within 180 days of submission to Sponsor 
Coronary Angiogram 
Within 180 days of scheduled implant procedure 
Pacemaker interrogation  
Within 180 days of scheduled implant procedure 
 
* TTE must be conducted after informed consent and must be collected according to echo core lab 
acquisition protocol. 
**pre-existing TEE/CT image of adequate quality capturing required anatomy for assessment can be used.   
Note: For all imaging (TTE, TEE, CT angiogram, coronary angiogram), if imaging is deemed incomplete or 
inadequate for assessment, repeat imaging may be required.   
Note: Procedure should be scheduled within 90 days of consent.  
 
During the follow up visits, medical information, findings and results will be entered in 
the appropriate electronic case report forms. 
 
Study patients who have signed the Informed Consent, have met all eligibility criteria, and 
have the study procedure attempted (at least skin incision to introduce the FORMA 
system) are considered enrolled in the study.  
 
Patients who enter the procedure room but who do not have the study procedure 
attempted (at least skin incision to introduce the FORMA system) will be classified as 
                                                 
7 If the screening echo confirms the PAP meets the study criteria, the right heart catheterization/ 
hemodynamic assessment at the baseline evaluation may be waived.   
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“non-implanted” and will be followed 30 days for safety. These patients will be exempt 
from all other study follow up visit procedures. 
 
 
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Table 13 – Summary of Required Study Procedures 
                                                 
1 Implant procedure should be scheduled within 90 days of consent. Patients who enter the procedure room but who do not have the study procedure attempted (at least skin incision to introduce the 
FORMA System) will be classified as “non-implanted” and will be followed 30 days for safety. These patients will be exempt from all other study follow up visit procedures. 
2 Discharge from hospital/unit post implant procedure. 
3 No changes in diuretics are allowed for at least 3 months post procedure unless patient presents with severe hypotension. 
4 βHCG for women who are not sterile or post-menopausal. 
5 Only required if an elevation was noted post implant (within 48 hours). 
6 mRS will be conducted at baseline for all patients with a history of stroke. For patients who experience a stroke during the study, mRS will be conducted closest to 90 days post event. It is recognized 
that an assessment of stroke is incomplete without an appropriate measurement of the disability resulting from the stroke, hence, mRS closest to 90 days post event will be used to assess clinical 
disability. Everey effort should be made to have a neurologist or neurology fellow perform the neurological assessments, or alternatively, a trained research team member certified in stroke 
assessment. mRS can be obtained by a certified research team member via phone interview with the patient or caregiver member if the patient is unable to visit the research office. 
STUDY PROCEDURES 
BASELINE 
IMPLANT 
PROCEDURE1 
(Day 0) 
DAY 1 
(24-48 hrs) 
DISCHARGE2  
1 MONTH 
 (30 ± 7 days ) 
6 MONTHS 
(180 ± 30 days) 
ANNUAL  
 (for 3 yrs)  
(365 ± 45 days) 
Informed Consent 
X 
 
 
 
 
 
 
Patient Demographics & Medical History 
X 
 
 
 
 
 
 
Clinical Evaluation/Concomitant Medications3 
X 
 
X 
X 
X 
X 
X 
Edema grading, ankle  circumference 
measurements &  Patient Edema Questionnaire 
X 
 
 
X 
X 
X 
X 
Hospitalizations &/or clinic visits &  paracentesis 
X 
 
 
 
X 
X 
X 
NYHA Class Assessment 
X 
 
 
 
X 
X 
X 
Health Status Questionnaires KCCQ, SF-12 
X 
 
 
 
X 
X 
X 
Six Minute Walk Test 
X 
 
 
 
X 
X 
X 
Katz Index (ADL),  Clinical Frailty Score© 
X 
 
 
 
 
 
 
 Patient Preference Survey 
X 
 
 
 
 
 
 
Safety Evaluation 
 
X 
X 
X 
X 
X 
X 
Pacemaker interrogation (pacemaker patients) 
X 
 
 
 
 
 
 
Coronary angiogram (within 1 year of procedure)  
X 
 
 
 
 
 
 
Complete Metabolic Panel and  Liver Panel  
X 
 
X 
X 
X 
X 
X 
CBC  and Platelet Count  
X 
 
X 
X 
X 
X 
X 
INR & PTT/aPTT  
X 
 
X 
X 
X 
X 
X 
βHCG 
X4 
 
 
 
 
 
 
Serum creatinine and eGFR 
X 
 
X 
X 
X 
X 
X 
Troponins and CK-MB 
X 
 
X 
X5 
 
 
 
ECG 
X 
 
X 
X 
X 
X 
X 
Transesophageal Echocardiogram 
X 
X 
 
 
 
 
 
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Transthoracic Echocardiogram 
X 
 
 
X 
X 
X 
X 
Pre-Implant Procedure Imaging  
(CT/ Angiographic Imaging & venogram for cardiac 
lead patients, if required) 
X 
 
 
 
 
 
 
Ventriculogram Imaging 
 
X 
 
 
 
 
 
Invasive Hemodynamic Monitoring 
X 
X 
 
 
 
 
 
Modified Rankin Scale  
X6  
 
 
X6 
X6 
X6 
X6 
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8.8 
MISSED PATIENT VISITS 
The Investigator shall inform study patients of the importance of returning for scheduled 
follow-up visits and reporting any address or telephone number changes.  The 
Investigator shall make every attempt to follow the study patients. 
 
The Investigator shall keep a separate log of the patients’ names and current contact 
information to facilitate their record keeping and ability to contact the patients for future 
follow-up.  If a patient cannot be reached for a follow-up assessment, the Investigator will 
document the missed visit and effort made to contact that patient, the patient’s primary 
health care provider, and/or hospital records on the appropriate Case Report Form.  
Patients who miss a visit will not be considered withdrawn, and an effort to contact them 
at the next follow-up visit interval will be made by the Investigator.   
8.9 
WITHDRAWAL CRITERIA AND PROCEDURES 
The Investigator will make every attempt to follow the patients at each of the required 
assessment periods. The reason for the withdrawal will be documented on the 
appropriate case report forms and in the medical records for each patient who has 
withdrawn.  
 
Patients may be withdrawn from the study for any of the following reasons:  
 
• Patient Withdrawal  
The patient may voluntarily withdraw from the clinical study at any time, without 
penalty or loss of benefits to which they are otherwise entitled.  
 
• Physician Withdrawal  
The Principal Investigator also has the right to withdraw a patient if s/he feels it is in 
the best interest of the patient to do so.  
 
•    Lost to Follow-up  
If a patient cannot be reached for a follow-up visit, the Investigator will document the 
contact efforts made to the patient and/or effort to obtain hospital records in the 
appropriate electronic case report form. If the patient cannot be reached in any way, 
or misses a visit, the patient will be considered “unable to contact” for that time 
interval. After three (3) documented attempts to make contact prove unsuccessful, a 
certified letter will be sent to the patient’s residence. If there is no response after the 
certified letter is sent, the patient will be considered “lost to follow-up.” 
 
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In all cases of withdrawal (as described above), withdrawn patients will not undergo 
further study follow-up procedures after the time of study exit. A study patient that has 
been withdrawn from the study will not be replaced. 
8.10 
PATIENT STUDY COMPLETION  
Study patients complete and exit the study when no additional follow-up visits, 
procedures, or data collection are required. Patients will then continue to be followed by 
their primary health care provider as required.   
 
A patient will also be exited from the study in the following instances:  
 
• Patient signs informed consent form, is deemed eligible but does not undergo the 
study procedure  
• 
Patient has study procedure attempted (at least skin incision to introduce the FORMA 
System) and does not have the investigational device implanted (will exit study at the 
1 month follow up visit)  
• 
If the study device is explanted, the patient will be followed for 30 days after the 
explant procedure for safety evaluations only, and will be exited from the study at 
that point. If one or more ongoing adverse event(s) related to the explant procedure 
is unresolved 30 days after the explant, the patient will remain in the study until the 
adverse event(s) have been resolved, or 180 days post explant, whichever comes first 
• 
Patient is lost-to-follow-up  
• 
Patient withdraws participation from the study or is withdrawn from the study 
• 
Patient expiration 
9 TRAINING  
9.1 
INVESTIGATORS DEVICE TRAINING 
 
 
 
   
 
 
9.2 
TRAINING OF INVESTIGATIONAL SITE PERSONNEL 
 
 
 
 
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9.3 
TRAINING DOCUMENTATION 
 
 
 
10 INVESTIGATIONAL DEVICE MANAGEMENT 
10.1 
DEVICE SHIPMENTS 
Devices will be transported to the study site when the Clinical Study Agreement is in place, 
the study site has obtained applicable regulatory (e.g., IRB, FDA) approvals, and a patient 
eligible for implant has been identified.   
 
Devices will be provided to the study site as needed for scheduled implant procedures.  
All investigational devices used in this study for investigational purposes will be labeled 
“Caution: Investigational Device, Limited by Federal (USA) law to investigational use”.   
10.2 
DEVICE ACCOUNTABILITY  
All device shipments will have inventory and shipment records. Devices may be hand 
carried to participating study sites by Study Sponsor personnel and will be accompanied 
by delivery of investigational device documentation (packing lists, transfer of 
investigational product form, etc). The Investigator(s) or designee will take inventory of 
the product and complete the delivery documentation with receipt date and signature. 
Both the study site and the Study Sponsor will retain copies of these documents. The 
Investigator will maintain a Device Accountability Log (as provided by the Sponsor) of all 
investigational devices documenting their receipt, disposition and return during this 
clinical study. The log will be kept with the documents for the clinical study and will be 
available for review during Study Sponsor monitoring visits. 
 
Upon Sponsor request or when enrollment has ended, FORMA System components must 
be returned to Edwards Lifesciences and the date of return must be recorded on the log. 
10.3 
DEVICE STORAGE 
The device inventory will be stored in a locked, controlled, cool and dry area as described 
in the IFU and/or presented on the device labeling.  This secured area will be only 
accessible to the Investigators or approved designee.  Only investigators trained and 
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identified in the Delegation of Authority form on file at Edwards Lifesciences may use the 
investigational devices. 
10.4 
DEVICE RETURN  
The Investigator will be notified in writing upon termination of the clinical study. All 
unused devices in original package and/or those in opened packages as well as those 
removed from the original package will be returned upon receipt of this notice.  The 
Investigator will receive instructions from the Study Sponsor on the return process. The 
Investigator’s copy of the Device Accountability log must document any unused devices 
that have been returned.  
 
Used devices may be handled and disposed of in the same manner as hospital waste and 
bio-hazardous materials in accordance with local regulations. There are no special risks 
related to the disposal of these devices. All returns and dispositions of devices will be 
captured on the Device Accountability Log Procedure needed. 
11 DATA COLLECTION AND REPORTING 
11.1 
DATA COLLECTION METHODS 
The Study Sponsor will provide the study site with the clinical protocol, electronic case 
report forms, sample informed consent form, and all other necessary study-related 
documents.  Study Sponsor’s Clinical Affairs Department, or designee, will conduct all 
aspects of data quality control and assurance of the study site including but not limited 
to, data reviewing, data monitoring, and form collection. 
11.2 
CASE REPORT FORMS 
Electronic CRFs will be used to collect all patient data during the study.  Paper copies will 
be available for printing on the website.  An e-mail notification will be sent to Edwards 
Lifesciences when enrollment data is collected into the website.  Electronic CRFs must be 
fully completed for each patient, and signed electronically by the investigator and/or 
designee. If for any reason the eCRFs are unavailable, or access to the electronic database 
is limited, paper CRF forms must be completed and submitted to study manager. The 
eCRFs should be completed at the first earliest opportunity. 
 
The investigator, or an individual designated by him/her, is responsible for recording all 
data from the study onto the eCRFs on a dedicated website.  All data entered is subjected 
to data type verification and range checking.  The operator is notified of errors that may 
occur, and depending on the data verification sub-routines, the operator might need to 
resolve that error before moving to the next entry field.  The investigator is required to 
provide an electronic signature on the appropriate eCRF pages to verify that he/she has 
reviewed the recorded data. 
 
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Completed eCRFs will be reviewed at the investigational site and remotely by authorized 
Edwards Lifesciences personnel at regular intervals throughout the study.  Each data 
record is evaluated with extensive electronic intra-form and inter-form edit checking at 
regular intervals.  If an error is discovered, the clinical site research Study Coordinator will 
be notified.  Corrections to the eCRFs will be made by the research Study Coordinator, 
approved by the investigator or designee and verified by the Sponsor. 
 
Data submission will be monitored closely. Sites that do not complete all data entry tasks 
in a timely manner may be prohibited from enrollment until data submission is current. 
 
The cycle of data editing will be ongoing until all the data are clean.  The Sponsor or 
designee will monitor the clinical site for source documentation verification.  If further 
data entry or source documentation errors are discovered during the site visit, additional 
queries will be generated and will have to be addressed by the clinical site. 
11.3 
SOURCE DOCUMENTATION REQUIREMENTS 
The Clinical Research Coordinator (CRC) designated by the Investigator, and documented 
on the Delegation of Authority log, will perform primary data collection drawn from 
source documentation review (patient’s medical record). All data that is entered in the 
eCRFs must have source documentation available in the patient medical records. Protocol 
deviation information can be recorded directly on the protocol deviation eCRF.  Data to 
be collected for the study purposes must not be entered directly onto eCRFs. The data 
must be recorded from original source documents and available for review by the study 
monitor. Regulations require that Investigators maintain information in the study 
patient’s medical records that corroborate data collected on the eCRFs. The source 
documentation may consist of but is not limited to: operative or procedure reports, 
progress notes, discharge summaries, laboratory reports, radiographic reports, 
medication logs, and worksheets. Source Documents may be in electronic form and/or 
hard (paper) copies. 
11.4 
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
Because of the potential for errors and inaccuracies in entering data into eCRFs, originals 
or photocopies of all relevant procedural records and reports, post-procedural 
examinations, laboratory and other test results may be kept on file in the Investigator’s 
patient study files.  Access to eCRFs and copies of test results must be available at all times 
for inspection by the study monitor. 
 
All clinical sites will be audited periodically by a study monitor employed by Edwards for 
protocol 
adherence, 
accuracy 
of 
eCRFs, 
and 
compliance 
to 
applicable 
regulations.  Evident patterns of non-compliance with respect to these standards will be 
cause for the site to be put on probation for a period of one month.  If corrective actions 
are not subsequently undertaken, the clinical site will be asked to withdraw. 
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Operational data is hosted for full security and availability internally by Edwards.  Edwards 
data management provides the highest standards of availability and security: 
 
• Hosting facility is a multi-level protected environment. 
• Access is severely restricted with high-end user recognition technology. 
• Multi-points backup of critical data is standard. 
• Firewalls and other undisclosed technologies provide strong data security. 
• Availability all year-round 24 hours a day. 
 
Passwords will be issued to appropriate data management personnel to ensure 
confidentiality and protection of the data by allowing variable levels of access to the 
computer system. 
12 REPORTABLE EVENTS / EFFECTS 
12.1 
DEFINITIONS 
12.1.1 ADVERSE EVENT  
An AE is defined in ISO 14155:2011 as any untoward medical occurrence, unintended 
disease or injury, or untoward clinical signs (including abnormal laboratory finding) in 
subjects, users or other persons, whether or not related to the investigational medical 
device. 
  
Note:  anticipated adverse events are adverse events that have been identified as possible 
adverse events related to the investigational medical device or the study procedure.  The 
anticipated events of this clinical study are outlined in Section 3.1, Potential Risks 
12.1.2 ADVERSE DEVICE EFFECT  
An adverse device effect (ADE) is defined in ISO 14155:2011 as any adverse event related 
to the use of an investigational medical device. This definition includes: 
- 
Adverse event resulting from insufficient or inadequate instructions for use, 
deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device. 
 
- 
Any event resulting from use error or from intentional misuse of the 
investigational medical device. 
12.1.3 SERIOUS ADVERSE EVENT  
A serious adverse event (SAE) is defined in ISO 14155:2011 as an adverse event that: 
1. led to death 
2. led to serious deterioration in the health of the subject that either resulted in : 
a. a life-threatening illness or injury, or 
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b. a permanent impairment of a body structure or a body function, or 
c. in-patient or prolonged hospitalization, or 
d. medical or surgical intervention to prevent life threatening illness or injury or 
permanent impairment to a body structure or a body function. 
3. led to fetal distress, fetal death or a congenital abnormality or birth defect (not 
anticipated in this study as pregnant women are excluded from the study). 
12.1.4 SERIOUS ADVERSE DEVICE EFFECT 
A serious adverse device effect (SADE) is defined in ISO 14155:2011 as an adverse device 
effect that resulted in any of the consequences characteristics of a serious adverse event 
or that might have led to any of these consequences if suitable action had not been taken 
or intervention had not been made or if circumstances had been less opportune.  
12.1.5 UNANTICIPATED SERIOUS ADVERSE DEVICE EFFECT  
Unanticipated adverse device effect (USADE) is defined in ISO 14155:2011 as any serious 
adverse device effect which by its nature, incidence, severity or outcome has not been 
identified in the risk analysis section of the study protocol. 
12.1.6 DEVICE DEFICIENCY AND MALFUNCTION  
 
Device deficiency is defined in ISO 14155:2011 as an inadequacy of a medical device with 
respects to its identity, quality, durability, reliability, safety or performance.  
 
Device malfunction is defined in ISO 14155:2011 as a failure of an investigational medical 
device to perform in accordance with its intended purpose when used in accordance with 
the Instructions for Use. 
 
Device deficiencies include malfunctions, use errors and inadequate labeling. 
 
All suspected device deficiencies, malfunctions or fractures of the study device will be 
documented on the appropriate eCRF.  In the event of a suspected device deficiency or 
other device issue, the device shall be returned to the Sponsor to the extent possible for 
analysis.  Investigational devices shall be returned to the Study Sponsor as described in 
Section 10.4. 
12.2 
REPORTING PROCEDURE 
Study patients will be carefully monitored during the clinical study (starting from the 
signing of inform consent) for any possible adverse event. All adverse events will be fully 
investigated by the Investigator. Appropriate treatment for the patient will be initiated 
while the study follow up continues. Adverse events will be followed until they are 
adequately resolved or explained. 
 
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The Investigator will attempt to assess the involvement of the investigational device and 
/ or study procedure in the adverse event. All observations and clinical findings, including 
the nature or the seriousness, will be documented on the appropriate case report form 
(CRF).  The investigator will classify the adverse events (AEs) based on the definitions in 
section 12.3 
 
Adverse events will be assessed by the Investigator for causality to the investigational 
device or index procedure as defined in MEDDEV 2.7/3 revision 3: 
 
Not related:  Relationship to the device or procedures can be excluded when: 
• The event is not a known side effect of the product category the device belongs 
to or of similar devices and procedures 
• The event has no temporal relationship with the use of the investigational device 
or the procedures 
• The serious event does not follow a known response pattern to the medical device 
(if the response pattern is previously known) and is biologically implausible 
• The discontinuation of medical device application or the reduction of the level of 
activation/exposure - when clinically feasible – and reintroduction of its use (or 
increase of the level of activation/exposure), do not impact on the serious event 
• The event involves a body-site or an organ not expected to be affected by the 
device or procedure 
• The serious event can be attributed to another cause (e.g. an underlying or 
concurrent illness/ clinical condition, an effect of another device, drug, treatment 
or other risk factors) 
• Harms to the subject are not clearly due to use error 
• In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the 
serious event 
Unlikely: The relationship with the use of the device seems not relevant and/or the event 
can be reasonably explained by another cause, but additional information may be 
obtained. 
 
Possible:  The relationship with the use of the investigational device is weak but cannot 
be ruled out completely. Alternative causes are also possible (e.g. an underlying or 
concurrent illness/ clinical condition or/and an effect of another device, drug or 
treatment). Cases were relatedness cannot be assessed or no information has been 
obtained should also be classified as possible. 
Probable: The relationship with the use of the investigational device seems relevant 
and/or the event cannot reasonably be explained by another cause, but additional 
information may be obtained. 
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Causal Relationship: The serious event is associated with the investigational device or 
with procedures beyond reasonable doubt when: 
• The event is a known side effect of the product category the device belongs to or 
of similar devices and procedures 
• The event has a temporal relationship with investigational device use/application 
or procedures 
• The event involves a body-site or organ that the investigational device or 
procedures are applied to or have an effect on 
• The serious event follows a known response pattern to the medical device (if the 
response pattern is previously known) 
• The discontinuation of medical device application (or reduction of the level of 
activation/exposure) and reintroduction of its use (or increase of the level of 
activation/exposure), impact on the serious event (when 
clinically feasible) 
• Other possible causes (e.g. an underlying or concurrent illness/ clinical condition 
or/and an effect of another device, drug or treatment) have been adequately 
ruled out 
• Harm to the subject is due to error in use 
 
In order to establish the relatedness, not all the criteria listed above might be met at the 
same time, depending on the type of device/procedures and the serious event 
 
The Investigator will report any serious adverse event, anticipated or unanticipated, to 
the Study Sponsor within three (3) calendar days after first knowledge of the event. 
Unanticipated Adverse Device Effects (UADE) should be reported to the Sponsor within 
three (3) calendar days. Notification to the Study Sponsor preferentially be made via the 
adverse event form in the electronic database (EDC). 
In the event that the EDC system is not accessible, the Sponsor may be notified initially 
 At the time of initial notification, the following 
minimal information should be provided: 
 
• Study site number 
• Patient ID 
• Date of event 
• Aware date  
• Adverse event description 
• Causal relationship to device and implant procedure 
The AE eCRF should be completed as soon as possible thereafter. 
 
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The Investigator (or designee) shall provide source documents related to reported 
adverse event as requested by Sponsor or their designee. 
 
The Sponsor will evaluate all adverse events for reportability as an UADE in accordance 
with 21 CFR part 812.46(b).  The Investigator and Sponsor will comply with reporting 
requirements per 21 CFR part 812.150.  A Sponsor who conducts an evaluation of an UADE 
under 812.46(b) shall report the results of such evaluation to FDA and to all reviewing 
IRB’s and participating Investigators within 10 business days after the Sponsor first 
receives notice of the event.  Thereafter the Sponsor shall submit such additional reports 
concerning the event as FDA requests. 
 
In addition, the Investigator will report all adverse events to their Institutional Review 
Board and / or National Regulatory Agency in accordance with the applicable 
requirements. 
 
Finally, the Investigator should follow all unresolved adverse events until the events are 
resolved or otherwise explained, or the patient is lost to follow-up or has withdrawn 
consent. 
12.3 
FINDINGS EXPECTED TO OCCUR WITH TREATMENT OF TRICUSPID 
REGURGITATION AND/OR INTERVENTIONAL CARDIAC PROCEDURES THAT DO 
NOT REQUIRE REPORTING TO THE SPONSOR 
For purposes of this study, the following findings are not considered adverse events 
requiring reporting to the Sponsor. These findings are normally expected to occur in 
association with treatment of tricuspid regurgitation, and/or are associated with 
customary, standard care of patients undergoing interventional cardiovascular 
interventions: 
• 
Post-procedure pain (within 48 hour of procedure) not requiring treatment or 
treated with non-opioids  
• 
Emesis, nausea, or headache (within 48 hours of procedure) associated with 
anesthesia 
• 
Out of range (outside the standard laboratory normal value) or “abnormal” lab 
values (including electrolyte imbalance) that are not clinically significant and do 
not require correction.  
Note: Abnormal lab values that roll up to a diagnosis should not be reported as 
separate AEs (e.g.  increased K+ in patient with renal insufficiency; elevated 
white blood count without signs or symptoms of infection)  
• 
Low grade temperature increase without signs and symptoms of infection 
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• 
Minor, localized tenderness, swelling, induration, oozing, etc. at access site(s) 
• 
Sinus bradycardia or tachycardia that does not require treatment or intervention 
• 
Systolic or diastolic blood pressure changes that do not require treatment or 
intervention 
• 
The need for insulin in a diabetic patient in the post op period 
This listing of events is intended to provide guidance to the investigational sites for the 
purpose of adverse event reporting.  The Investigator should utilize his/her clinical 
judgment in evaluating adverse experiences, and may decide that the above events 
should be reported as adverse events. 
12.4 
DEATHS AND EXPLANTS 
12.4.1 PATIENT DEATHS 
Patient death occurring during the study should be reported to the Sponsor or designee 
within one (1) business day of Investigator’s knowledge of the death.  The Adverse Event 
that resulted in death should be entered in the database on the Adverse Event form 
within one (1) business day and include a brief description of the relevant clinical 
information leading to the death of the patient. In the event of patient death, every effort 
should be made to obtain a copy of the autopsy report and/or death summary.  
Information on the cause of death and its relationship to the investigational device or 
study procedure will be determined by the Investigator. Copies of an autopsy report, if 
available, and/or a death summary are to be forwarded to the Study Sponsor.  
 
If a device is explanted during autopsy, the device should be returned to the Study 
Sponsor for analysis.  Return kits for devices will be provided upon request by the clinical 
monitor.  In addition, patient death must be reported to the IRB in accordance with IRB 
requirements. 
12.4.2 DEVICE EXPLANTS 
If the study device is explanted in the intra-operative or early post-operative period a copy 
of the explant procedure report must be provided to the Study Sponsor. Information on 
the cause of explant and its relationship to the study devices will be determined by the 
Investigator. Explanted study devices during this period must be returned to Study 
Sponsor for analysis.   
 
If the study device is explanted in the late post-operative period, every effort should be 
made to obtain a copy of the explant procedure report, as applicable. Information on the 
cause of explant and its relationship to the study device will be determined by the 
Investigator. Copies of an explant report, if available, are to be sent to the Study Sponsor. 
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Investigational devices shall be returned to the Study Sponsor as described in Section 
10.4. 
13 STATISTICAL ANALYSIS 
13.1 
SAMPLE SIZE  
This clinical study will enroll 60 patients. This sample size was established based on typical 
sample sizes for early feasibility studies and no statistical justification was utilized. 
13.2 
ANALYSIS POPULATION 
Analysis populations are defined below:  
 
• Intent-to-treat population  
The intention-to-treat (ITT) population includes all patients who signed 
informed consent, met eligibility criteria, and in whom the study procedure 
has been attempted (i.e. at least skin incision to introduce the FORMA 
System). 
 
• As-treated  population  
The as-treated population is a subset of ITT population and includes all 
patients in whom the study device is implanted and remains in position at the 
time of the patient’s exit from the procedure room. 
 
• Per-protocol population 
The per-protocol (PP) population is a subset of as-treated (implanted) 
population in whom there are no  inclusion/exclusion criteria-related protocol 
deviations. 
 
The as-treated population will be the primary analysis population for performance and 
safety assessment.  The ITT population will be used for device success, and additional 
safety analysis. Additional analyses of performance and safety data using the PP 
population will also be performed, if there is a clinically meaningful difference in sample 
size from the as-treated population. 
  
13.3 
DEVICE SUCCESS ENDPOINT ANALYSIS 
The device success endpoint will be summarized by counts and percentages for the ITT 
and as-treated cohort.  The endpoint will be assessed at the 1 month, 6-month, 1 year, 2-
year and 3-year follow-up intervals.    
 
In addition to the device success analysis, hemodynamic performance data will be 
obtained at the following time points: baseline, 1 month, 6 months and annually up to 3 
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years. Descriptive statistics such as mean, standard deviation will be calculated for the 
continuous echo variables as well as the change from baseline for each variable. 
13.4 
PROCEDURE SUCCESS ENDPOINT ANALYSIS 
The procedure success endpoint will be summarized by counts and percentages for the 
as-treated cohort.  The endpoint will be assessed at the index procedure hospital 
discharge.  
13.5 
CLINICAL SUCCESS ENDPOINT ANALYSIS 
The clinical success endpoint will be summarized by counts and percentages for the as-
treated cohort.  The endpoint will be assessed at the 1 month follow-up interval.   
 
Patient specific functional status (NYHA Class), exercise capacity (6MWT), blood test 
parameters, and quality of life (SF-12 and KCCQ) metrics will be assessed at baseline, 1 
month, 6 months and annually up to 3 years.  The distribution (numbers of patients and 
percentages) in the various NYHA classes will be tabulated at baseline, 1 month, 6 months 
and annually up to 3 years.  Patients that are missing a baseline or follow up values will 
be excluded from the analysis.  Patients that undergo any type of repair or replacement 
procedure for the tricuspid valve will be excluded from these analyses at the time of the 
reintervention and summarized in a table. 
 
Rehosptilization rates will be assessed at 1 month, 6 months and annually up to 3 years. 
13.6 
ADDITIONAL SAFETY ANALYSIS  
In addition to the above endpoints, a listing of all the AEs and SAEs for the entire study 
population will be provided. 
13.7 
MISSING DATA  
All possible steps will be taken to minimize missing data in the study, including monitoring 
of data forms for completeness by the sponsor and efforts to track and maintain contact 
with study patients during the follow-up period by the investigational sites.  
 
Unless otherwise specified, all statistical analyses for the endpoints will be performed 
using available data. No missing value imputation will be performed. 
13.8 
ANALYSIS SOFTWARE 
 
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14 MONITORING 
14.1 
MONITORING METHODS  
A study monitor will be assigned to monitor the progress of the study by the Study 
Sponsor.  The study monitor will remain in close contact with the study site throughout 
the duration of the study to provide any needed materials, (i.e. study forms, etc.) answer 
any questions and ensure that proper staffing levels are being maintained by the 
Investigator.  The study monitor will be responsible for verifying that patients have signed 
the informed consent as required by regulations, reviewing the data recorded on the 
eCRFs and visiting the study site periodically to observe study progress and compliance 
with the study protocol and regulations applicable to this clinical study. 
 
Monitoring visits will be scheduled throughout the duration of the clinical study between 
the monitor and the Investigator at a mutually convenient and available time.  These visits 
will assure that the facilities are still acceptable, the study protocol is being followed, the 
IRB and FDA have been notified of approved protocol changes as required, complete 
records are being maintained, appropriate timely reports have been made to the Study 
Sponsor and the IRB, device and device inventory are controlled and the Investigator is 
carrying out all agreed activities. Any personnel changes must be reported to the study 
monitor immediately and a training program scheduled and documented.  
14.2 
MONITORING PLAN 
Prior to patient enrollment, an initiation visit will be completed at the study site to ensure 
the following:   
 
1. 
IRB and applicable regulatory body approvals have been obtained and 
documented,  
2. 
The Investigator(s) and study personnel are appropriately trained and clearly 
understand the study,  
3. 
The Investigator(s) and study personnel accept the obligations incurred in 
undertaking this clinical study, 
4. 
The Delegation of Authority form has been completed properly. 
 
Periodic monitoring visits will be made at the enrolling study site in accordance with site 
enrollment rates. The study site should be visited a minimum of twice per year by the 
study monitor. 
 
Upon termination or conclusion of the study, the study monitor will perform a close-out 
visit.   
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14.3 
PROTOCOL DEVIATION  
A protocol deviation is defined as an event where the Investigator or a study personnel 
did not conduct the study according to the clinical protocol.  Investigators shall be 
required to obtain proper approval from the Study Sponsor before initiating deviations 
from the study protocol, except where necessary to protect the life or physical well-being 
of a patient in an emergency.  If an Investigator or designee contacts a Clinical Affairs 
representative to obtain prior approval for a change to the clinical study requirements, 
the approval or disapproval will be documented in writing. A copy of the approval or 
disapproval will be forwarded to the Investigator and a copy will be maintained in the 
study files. Prior approval is generally not expected in situations where unforeseen 
circumstances are beyond the Investigator’s control, (e.g. patient did not attend 
scheduled follow-up visit, etc.) however the event is still considered a deviation.   
 
Deviations shall be reported to the Study Sponsor regardless of whether medically 
justifiable, pre-approved by the Sponsor, or taken to protect the patient in an emergency.  
Patient specific and non-patient specific deviations, (e.g. unauthorized use of an 
investigational device outside the study, unauthorized use of an investigational device by 
a physician who is not listed in the Delegation of Authority Log etc.) will be reported to 
the Sponsor. Patient specific deviation information must be recorded directly on the 
Protocol Deviation eCRF and non-patient specific deviations will be recorded in writing. 
Investigators will also adhere to procedures for reporting study deviations to their IRB in 
accordance with their specific reporting policies and procedures. 
 
A major protocol deviation or noncompliance is one that may have a significant impact 
on subject safety, well-being, the subject’s willingness to participate in the study, or that 
may compromise the integrity of the study data and analysis, including:  
 
a) Subject implanted/treated with study device not having met eligibility criteria 
at the time of implant/treatment.  
b) Informed Consent not signed or signed after the initiation of non-standard of 
care, research related assessments.  
c) UADE not reported to IRB/EC/Sponsor within the required timeframe  
d) Unauthorized use/implant of an investigational device  
A minor protocol deviation or noncompliance is unlikely to have a significant impact on 
subject safety, wellbeing, or is unlikely to compromise the integrity of the study data and 
analysis.  All protocol deviations or noncompliance will be reported to the IRB/EC, as 
required.  
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14.4 
COMMUNICATION PROCEDURES 
During the course of the study, all correspondence (letters, telephone call, emails and 
faxes) regarding the study must be maintained in the study binder provided by the Study 
Sponsor.  This binder must be made available for monitoring visits or audits. 
15 DATA MONITORING COMMITTEE 
The Study Sponsor with an independent Data Monitoring Committee (DMC) will monitor 
all safety data.  The DMC will consist of a minimum of 3 members, all members being 
physicians; one cardiothoracic surgeon, one interventional cardiologist and one 
cardiologist.   
 
DMC activities, including stopping rules, will be defined in DMC Charter. 
 
With regards to Safety oversight committee, in case of inconsistency between the 
protocol and the Safety oversight committee’s charter (e.g. DMC), the charter will be the 
final determining document. 
 
16 APPLICABLE REGULATIONS AND GUIDELINES  
The regulations listed in Table 13 must be observed to comply with the Study Sponsor 
policy for conduct and of clinical studies; they also represent sound research practice.  It 
is the responsibilities of the Investigator(s) to comply with the requirements set forth in 
their country specific regulations.   
 
Table 13 – Applicable Regulations and Guidelines 
Region 
Regulation / Guideline 
United States 
- 21 CFR 50 – Protection of Human Patients 
- 21 CFR 56 – Institutional Review Boards 
- 21 CFR 54 – Financial Disclosure by Clinical Investigators 
- 21 CFR 58 – Good Laboratory Practice for Nonclinical Laboratory 
Studies 
- 21 CFR 812: Investigational Device Exemptions 
- 21 CFR 820 – Quality System Regulation 
- ISO 13485:2016 Medical Devices – Quality Management Systems 
– Requirements for Regulatory Purposes 
- ISO 14155:2011 I (Clinical Investigation of Medical Devices for 
Human Patients 
- ISO 14971:2012 (Application of risk management to medical 
devices) 
 
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Furthermore, the Investigator(s) must comply with the requirements of the Declaration 
of Helsinki (2008) and with of ICH E6 GCP or with laws of the foreign country, whichever 
will afford greater protection to the patient screened for participation in the clinical study 
and patients who participate in the study. 
16.1 
DATA PROTECTION AND PATIENT CONFIDENTIALITY 
The Study Sponsor is dedicated to maintaining the confidentiality and privacy of patients 
who volunteer to participate in the study.  Passwords are issued to appropriate personnel 
to insure confidentiality and protection of the database by allowing variable levels of 
access to the computer system. In addition, the Principal Investigator is responsible for 
maintaining confidentiality throughout the clinical study. The hard copies of the source 
documentation are to be maintained in a secure area with limited access.  All patient 
identifiers will be obliterated from all photocopies of source documents that have been 
removed from the study site.  Patient identifiers include, but are not limited to: patient’s 
name, social security number or equivalent, and medical / hospital number.  All study 
documents for the clinical study will identify the patient by a patient study identification 
number assigned by the Sponsor and the patient’s initials. 
16.2 
INVESTIGATOR RESPONSIBILITIES 
16.2.1 GENERAL DUTIES 
The Investigator shall ensure that all work and services described herein, or incidental to 
those described herein, shall be conducted in accordance with the highest standards of 
medical and clinical research practice and the applicable regulations.  The Investigator 
shall be responsible for the day to day conduct of the clinical study and for the safety and 
well-being of patients enrolled. The Investigator will provide copies of the current study 
protocol to all staff responsible for study conduct. 
 
The Investigator is responsible for obtaining and maintaining IRB approval for the study 
at his/her study site.   
 
If there is a change or addition of an Investigator, an amended Clinical Study Agreement 
must be completed promptly. 
16.2.2  INVESTIGATOR RECORDS 
The Investigator will maintain the accurate, complete, and current records relating to 
participation in this clinical study.  Study records including CRFs and supporting data, 
signed Clinical Study Agreement, protocols and protocol amendments, signed informed 
consents,  device tracking logs, IRB approval letters, IRB submissions, correspondence, 
including required reports, and other documents pertaining to the conduct of the study 
must be kept on file by the Investigator.  If the Investigator wishes to assign the 
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responsibility of maintaining the study files to someone else or move them to another 
location, he/she should consult with the Study Sponsor in writing regarding the change.   
Upon Study completion, the study files must be maintained in a known location for a 
period in accordance with local regulatory requirements.   
16.2.3  INVESTIGATOR REPORTS 
 
 
 
 
 
   
 
  
 
   
 
 
 
 
 
 
   
 
 
   
 
 
 
. 
16.3 
SPONSOR RESPONSIBILITIES 
16.3.1 GENERAL DUTIES 
As the Study Sponsor of this clinical study, Edwards Lifesciences has the overall 
responsibility for the conduct of the study, including assurance that the study meets the 
regulatory requirements of the pertinent regulatory agencies.   
 
In addition, the Study Sponsor declares that no employee/affiliate of the Sponsor or 
Investigator will be included or encouraged to participate in this investigational study. 
 
The Study Sponsor will inform the Investigator of any new information about the study 
that may affect the health, safety or welfare of the patients or which may influence 
patient’s decision to continue participating in the study. 
16.4 
SELECTION OF INVESTIGATORS   
 
 
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16.4.1 MONITORING THE STUDY  
The Study Sponsor will ensure compliance with the signed clinical agreement, the 
protocol (investigational plan), the requirements of applicable regulations and guidelines 
(see section 16.1) and any conditions of study approval by the IRB and regulatory bodies. 
Edwards will conduct an immediate investigation of any unanticipated adverse device 
effects (UADE) and if an event is found to present an unreasonable risk to study patients, 
the Study Sponsor will inform Investigators, IRBs, and regulatory bodies as required. 
16.4.2 SPONSOR RECORDS  
The Study Sponsor will maintain accurate, complete, and current records relating to this 
clinical study.  Study records include CRFs, signed Clinical Study Agreement, signed 
financial disclosure, protocols and protocol amendments, informed consent, device use, 
IRB approval letters, submissions, correspondence, including required reports, and other 
documents.  The Study Sponsor will maintain study documentation during the study and 
for a period in accordance with local regulatory requirements after the study is 
terminated or completed, or the study records are no longer required to support a 
regulatory submission.  Storage of the study records may be designated to a third party.  
16.4.3 SPONSOR REPORTS 
 
 
 
 
 
 
 
   
 
 
     
 
 
 
 
 
 
 
 
 
 
 
 
   
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16.5 
STUDY CHANGES 
Changes in the protocol may be made only by written amendment agreed upon by the 
Study Sponsor, the regulatory agency and IRB.  As appropriate, the Study Sponsor will 
submit protocol amendments to the pertinent regulatory agencies and Investigators to 
obtain IRB approval prior to implementation. 
16.6 
 STUDY COMPLETION OR TERMINATION AND CLOSE-OUT 
The Investigator will be notified in writing upon termination/conclusion of the study.  
Edwards Lifesciences retains the right to suspend or terminate this clinical study at any 
time. 
 
Safety and review committees associated with the study may recommend termination 
should safety concerns warrant such action as described in Section 15. 
 
All study patients enrolled up to the point of study termination, will continue to be 
followed as per protocol requirements.  
16.7 
AUDITS AND INSPECTIONS 
In the event that audits are initiated by the Study Sponsor or national/international 
regulatory authorities, the Investigator shall allow access to the original medical records 
and provide all requested information, as applicable. 
16.8 
PUBLICATION POLICY 
 
 
 
 
   
 
 
 
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17 REFERENCES 
 
1. 
Nath, J., E. Foster, and P.A. Heidenreich, Impact of tricuspid regurgitation 
on long-term survival. Journal of the American College of Cardiology, 2004. 
43(3): p. 405-409. 
2. 
Nishimura, R.A., et al., 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 Practice Guidelines. J 
Thorac Cardiovasc Surg, 2014. 148(1): p. e1-e132. 
3. 
Dreyfus, G.D., S.G. Raja, and K.M.J. Chan, Tricuspid leaflet augmentation to 
address severe tethering in functional tricuspid regurgitation. European 
Journal of Cardio-Thoracic Surgery, 2008. 34(4): p. 908-910. 
4. 
Benedetto, U., et al., Prophylactic tricuspid annuloplasty in patients with 
dilated tricuspid annulus undergoing mitral valve surgery. The Journal of 
thoracic and cardiovascular surgery, 2012. 143(3): p. 632-8. 
5. 
Raja, S.G. and G.D. Dreyfus, Surgery for functional tricuspid regurgitation: 
current techniques, outcomes and emerging concepts. Expert Rev 
Cardiovasc Ther, 2009. 7(1): p. 73-84. 
6. 
Chang, B.C., et al., Long-term clinical results of tricuspid valve replacement. 
Annals of Thoracic Surgery, 2006. 81(4): p. 1317-1324. 
7. 
Vahanian, A., et al., Guidelines on the management of valvular heart 
disease (version 2012): the Joint Task Force on the Management of 
Valvular Heart Disease of the European Society of Cardiology (ESC) and the 
European Association for Cardio-Thoracic Surgery (EACTS). Eur J 
Cardiothorac Surg, 2012. 42(4): p. S1-44. 
8          Campelo-Parada F, Perlman G, Philippon F, et al. First-in-man experince of 
a novel transcatheter repair system for treating severe tricuspid 
regurgitation. J Am Coll Cardiol. 2015;66:2475-2483 
9          Perlman, G., et al., Transcatheter Tricuspid Valve Repair With a New 
Transcatheter Coaptation System for the Treatment of Severe Tricuspid 
Regurgitation. Journal of American College of Cardiology: Cardiovascular 
Interventions, 2017. 10 (19) p. 1994-2003. 
10.       Abbas, A.E., et al., A simple method for noninvasive estimation of 
pulmonary vascular resistance.  Journal of American College of Cardiology, 
2003. 41(6): p. 1021-7. 
 
 
 
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18 DEFINITIONS  
 
Access Site 
(VARC-1) 
Any location (arterial or venous) traversed by a guidewire, a 
catheter or a sheath (including the subclavian or axillary vein) 
Access Site and 
Vascular 
Complications 
(MVARC) 
I. Vascular complications 
A. Major access site vascular complications, including: 
i. Aortic dissection or aortic rupture, or 
ii. Access site-related† arterial or venous injury (dissection, 
stenosis, ischemia, arterial, or venous thrombosis including 
pulmonary emboli, perforation, rupture, arteriovenous fistula, 
pseudoaneurysm, hematoma, retroperitoneal hematoma, atrial 
septal defect‡), irreversible nerve injury, or compartment 
syndrome resulting in death; hemodynamic compromise; life-
threatening, extensive, or major bleeding (MVARC bleeding 
scale); visceral ischemia; or neurological impairment, or 
iii. Distal embolization (noncerebral) from a vascular source 
requiring surgery or resulting in amputation or irreversible end-
organ damage, or 
iv. Unplanned endovascular or surgical interventions resulting in 
death; life-threatening, extensive, or major bleeding (MVARC 
bleeding scale); visceral ischemia; or neurological impairment 
B. Minor access site vascular complications, including: 
i. Access site arterial or venous injury (dissection, stenosis, 
arterial, or venous thrombosis including pulmonary emboli, 
ischemia, 
perforation, 
rupture, 
arteriovenous 
fistula, 
pseudoaneurysm, hematoma, retroperitoneal hematoma, atrial 
septal defect‡) not resulting in death; life-threatening, 
extensive, or major bleeding (MVARC scale); visceral ischemia; or 
neurological impairment, or 
ii. Distal embolization treated with embolectomy and/or 
thrombectomy not resulting in amputation or irreversible end-
organ damage, or 
iii. Any unplanned endovascular stenting or unplanned surgical 
intervention not meeting the criteria for a major vascular 
complication, or 
iv. Vascular repair (via surgery, ultrasound-guided compression, 
transcatheter embolization, or stent-graft) 
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II. Cardiac structural complications due to access-related issues 
A. Major cardiac structural complications, including: 
i. Cardiac perforation* or pseudoaneurysm resulting in death, 
life-threatening bleeding, hemodynamic compromise, or 
tamponade, or requiring unplanned surgical or percutaneous 
intervention 
B. Minor cardiac structural complications, including: 
i. Cardiac perforation or pseudoaneurysm not meeting major 
criteria 
*Including the right ventricle, right atrium, coronary sinus, right 
atrium, and right ventricle.  
†May arise from the access procedure per se or complications 
from vascular closure devices.  
‡Meeting 
pre-specified 
criteria 
for 
a hemodynamically 
significant shunt, or requiring unplanned percutaneous or 
surgical closure. 
Access Site and 
Vascular 
Complications 
Requiring 
Intervention 
Complications (i.e. dissection, perforation, arteriovenous fistula, 
pseudoaneurysm 
formation, 
retroperitoneal 
hemorrhage, 
thromboembolism) requiring intervention (percutaneous or 
surgical). 
ACT 
Activated clotting time 
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Acute Kidney Injury 
(AKI) 
(MVARC) 
Maximal change in serum Creatinine (sCR) from baseline to 7 
days post-procedure 
 
Stage 1:  
Increase in sCr to 150%–199% (1.50–1.99 x increase vs. baseline), 
increase of ≥0.3 mg/dl (≥26.4 mmol/l) within 48 h, or urine 
output <0.5 ml/kg/h for ≥6 h but <12 h 
 
Stage 2: 
Increase in sCr to 200%–299% (2.00–2.99 x increase vs. baseline) 
or urine output <0.5 ml/kg/h for ≥12 h but <24 h 
 
Stage 3:  
Increase in sCr to ≥300% (>3.0 x increase vs. baseline), sCr of ≥4.0 
mg/dl (≥354 mmol/l) with an acute increase of ≥0.5 mg/dl (44 
mmol/l), urine output <0.3 ml/kg/h for ≥24 h, or anuria for ≥12 
h; patients receiving renal replacement therapy are considered 
stage 3 irrespective of other criteria. 
Adverse Device Effect 
(ADE) 
Refer to ISO 14155 definition 
Adverse Event (AE) 
(ISO 14155:2011) 
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 investigational medical 
device 
Anchor Detachment 
Anchor has detached from original implanted position and is 
not attached to any structure, Spacer is still within the tricuspid 
valve (therapeutic)  
Anchor Detachment 
with Spacer Migration 
Anchor has detached from original implant position and is not 
attached to any structure, Spacer is no longer within the 
tricuspid valve (non-therapeutic)  
Anchor Migration 
Anchor has migrated and attached to a different 
structure/location than original implanted position, Spacer is 
still within the tricuspid valve (therapeutic)  
Anchor Migration 
with Spacer Migration 
Anchor has migrated and attached to a different 
structure/location than original implanted position, Spacer is no 
longer within the tricuspid valve (non-therapeutic)  
Bleeding  
(MVARC) 
Endpoint is severe bleeding, defined as major, extensive, life-
threatening or fatal bleeding. 
 
All bleeding events will be classified as: 
 
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I. Minor 
Any overt*, actionable sign of hemorrhage (e.g., more bleeding 
than would be expected for a clinical circumstance, including 
bleeding found by imaging alone) that meets ≥1 of the 
following: requiring nonsurgical medical intervention by a 
health care professional; leading to hospitalization or increased 
level of care; prompting evaluation; or requires 1 or 2 U of 
whole blood or packed RBC transfusion and otherwise does not 
meet criteria for major, extensive, or life threatening bleeding. 
 
II. Major 
Overt bleeding either associated with a drop in the hemoglobin 
of ≥3.0 g/dl or requiring transfusion of ≥3 U of whole blood or 
packed RBCs AND does not meet criteria of life-threatening or 
extensive bleeding. 
 
III. Extensive 
Overt source of bleeding with drop in hemoglobin of ≥4 g/dl or 
whole blood or packed RBC transfusion ≥4 U within any 24-h 
period, or bleeding with drop in hemoglobin of ≥6 g/dl or whole 
blood or packed RBC transfusion ≥4 U (BARC type 3b) within 30 
days of the procedure. 
 
IV. Life-threatening 
Bleeding in a critical organ, such as intracranial, intraspinal, 
intraocular, or pericardial necessitating surgery or intervention, 
or intramuscular with compartment syndrome OR bleeding 
causing hypovolemic shock or hypotension (systolic blood 
pressure <90 mm Hg lasting >30 min and not responding to 
volume resuscitation) or requiring significant doses of 
vasopressors or surgery. 
 
V. Fatal 
Bleeding adjudicated as being a proximate cause of death. 
Severe bleeding adjudicated as being a major contributing 
cause of a subsequent fatal complication, such as MI or cardiac 
arrest, is also considered fatal bleeding. 
 
 
*“Overt” bleeding is defined as clinically obvious (visible 
bleeding and bleeding identified by imaging only). Examples of 
overt bleeding include: 
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o Pseudoaneurysm 
o Retroperitoneal hematoma seen on CAT scan 
o Visible access site hematoma 
o Gross hematuria  
o Hematemesis and hematochezia 
 
Procedural bleeding has to be an overt bleeding from vascular 
system either at or remote from the access/surgical site.  
 
With respect to blood transfusions, it is critical to acknowledge 
that a bleeding complication has to be the result of overt 
bleeding and cannot be adjudicated based on blood 
transfusions alone. Prophylactic transfusion given for reasons 
other than due to the overt bleeding will not be considered as a 
bleeding event. 
 
If the reason for Hgb drop was other than due to the overt 
bleeding i.e. due to hemodilution, chronic iron deficiency 
anemia, this will not be considered as a bleeding event. 
 
For purposes of calculating the drop in hemoglobin during the 
index hospitalization, the Hgb value identified closest to the 
beginning of the index procedure, before the occurrence of 
bleeding event, will be used as the baseline value.   
 
If the bleeding event occurs after discharge from index 
procedure, the Hgb value just prior to the occurrence of 
bleeding event will be the baseline value for calculating the 
drop in Hgb.  
 
Timing of a bleeding event that meets MVARC criteria is based 
on the time and date of transfusion or the first Hgb drop, 
whichever occurs first.  
 
To calculate the total number of transfusions given, consider 
only units given to treat the bleeding event itself. Transfusions 
given before the procedure should not be combined with the 
units given for the bleeding event 
 
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Cardiac Tamponade 
Pressure on the heart that occurs when blood or fluid builds up 
in the space between the heart muscle (myocardium) and 
the outer covering sac of the heart (pericardium).  
Cardiovascular 
Mortality 
see “Death” 
Cerebrovascular 
Accident (CVA) 
See “Stroke” 
Clinical Success 
Clinical success: procedural success without MAEs at 30 days. 
Clinical Frailty Scale© 
A 9 point single question administered  to measure frailty.  
Developed by the Canadian Study of Health and Aging (CSHA). 
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Death 
(MVARC) 
Cardiovascular (CV) Death 
 
The primary cause of CV death will be categorized using the 
following choices: 
 
o Arrhythmia and/or conduction system 
disturbance 
o Cardiovascular infection and sepsis (e.g. 
Endocarditis) 
o Device failure 
o Heart failure  
o Major bleeding 
o Myocardial Infarction 
o Stroke 
o Sudden, unexpected death / unknown 
o Tamponade  
o Thromboembolism  
o Other CV cause 
 
If death was due to a heart failure, it will be sub classified into: 
 
o LV dysfunction 
o RV dysfunction 
o Biventricular dysfunction 
 
Non-Cardiovascular (CV) Death 
 
A diagnosis of non-CV death requires the primary cause to be 
clearly related to another condition due primarily to an 
identifiable non-CV cause or etiology. Specific diagnoses may 
include respiratory failure, pneumonia, trauma, suicide, or any 
other non-cardiovascular defined causes (e.g., liver disease, 
malignancies etc.) not included in the previous categories. 
 
Primary cause of non-CV death 
 
The primary cause of non-CV death will be categorized using the 
following choices: 
 
o Adverse drug reaction or overdose 
o Cancer 
o Gastrointestinal 
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o Liver failure  
o Non-cardiovascular infection and sepsis (e.g. 
pneumonia) 
o Pancreatic 
o Renal failure  
o Respiratory Failure 
o Trauma  
o Other non-CV cause 
 
Device Deficiency 
(ISO 14155:2011) 
An inadequacy of a medical device with respects to its identity, 
quality, durability, reliability, safety or performance. Device 
deficiencies include malfunctions, use errors and inadequate 
labeling. 
Device Fracture 
Break or other structural defect in anchor, railing, or spacer with 
or without embolization 
Device Malfunction 
Device malfunction is defined in as a failure of an investigational 
medical device to perform in accordance with its intended 
purpose when used in accordance with the Instructions for Use. 
See “Device Deficiency” 
Device Success 
Device is deployed as intended and the delivery system is 
successfully retrieved as intended at the time of the patient’s exit 
from the cardiac catheterization laboratory.  
eGFR 
Estimated glomerular filtration rate 
Embolism 
Free flowing blood clot or lesion material that is located in the 
systemic or pulmonary circulation. 
 
A peripheral embolic event is an operative, autopsy or clinically 
documented embolus that produces symptoms from complete 
or partial obstruction or a peripheral (noncerebral) artery.   
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Emergency Cardiac 
Surgery 
Emergent Salvage:  The patient is undergoing CPR en route to the 
operating room or prior to anesthesia induction 
 
Emergent:  The patient’s clinical status includes any of the 
following: 
1. Ischemic dysfunction of any of the following: 
a. ongoing ischemia including rest angina despite 
maximal medical therapy (medical and/or IABP); 
b. Acute Evolving Myocardial Infarction within 24 hours 
before surgery or 
c. pulmonary edema requiring intubation 
2. Mechanical dysfunction (either of the following):  
a. shock with circulatory support; or 
b. shock without circulatory support. 
 
Urgent: All of the following conditions are met: 
• Not elective status 
• Not emergent status 
• Procedure required during same hospitalization in order to 
minimize chance of further clinical deterioration 
• Worsening, sudden chest pain, CHF, acute myocardial 
infarction (AMI), anatomy, IABP, unstable angina with 
intravenous (IV) nitroglycerin (NTG) or rest angina may be 
included. 
 
Elective:  The patient’s cardiac function has been stable in the 
days or weeks prior to the operation. The procedure can be 
deferred without increased risk of compromised cardiac 
outcome. 
Endocarditis  
An inflammation of the inside lining of the heart chambers and 
heart valves (endocardium).  Endocarditis can involve the heart 
muscle, heart valves, or lining of the heart. 
Enrollment 
Patient will be considered “provisionally enrolled” when they 
have signed the informed consent form agreeing to participate 
in the study and have been deemed eligible for study 
participation by meeting the study criteria. A patient will be 
considered “enrolled” at the time of skin incision to introduce 
the FORMA System into the body. 
Explant  
Removal of the study device after completion of the implant 
procedure for any reason. 
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Heart Failure 
Heart Failure - A progressive condition that involves loss of 
pumping ability by the heart (heart muscle weakens and 
gradually loses its ability to pump enough blood through the 
body), generally accompanied by fluid accumulation in body 
tissues, especially the lungs. 
 
Heart Failure Hospitalization - An unplanned hospitalization that 
results in at least one overnight stay (i.e., where the admission 
date and the discharge date are different) that includes 
increased signs and/or symptoms of worsening heart failure and 
requires the administration or augmentation of existing heart 
failure therapy. 
 
Severe Heart Failure – See NYHA Class IV 
HEART Team (local) 
The local ‘HEART Team', for the purpose of this study, must 
include a minimum of one Cardiologist, and one Cardiac Surgeon. 
Hemolysis 
(Device Hemolysis) 
Rupturing of red blood cells (erythrocytes) and the release of 
their contents (cytoplasm) into surrounding fluids. 
 
Device hemolysis is defined as hemolysis in or near the 
investigational device that interferes with the function of the 
device.  Device hemolysis related thrombus may be confirmed by 
operation, autopsy, or diagnostically by such methods as 
echocardiography, angiography, or magnetic resonance imaging. 
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Hospitalization/ 
Rehospitalization 
Hospitalization is defined as any unplanned admission to the 
hospital (including an emergency department visit) for either a 
diagnostic or therapeutic purpose following discharge from the 
index hospitalization. 
 
All hospitalizations will be classified to determine whether the 
hospitalization was related to: 
o CHF (Congestive Heart Failure) hospitalization: a 
hospital stay for ≥ 24 hours with signs and/or laboratory 
evidence of worsening heart AND administration of 
intravenous or mechanical heart failure therapies. An ER 
stay for ≥ 24 hours would qualify as a CHF hospitalization 
endpoint, even absent formal hospital admission, as such 
a prolonged stay represents a severe episode of heart 
failure. 
o Other CV hospitalization: hospitalization due for 
coronary artery disease, acute myocardial infarction, 
hypertension, 
cardiac 
arrhythmias, 
cardiomegaly, 
pericardial effusion, atherosclerosis, stroke, or peripheral 
vascular disease without qualifying heart failure. 
o Non-CV hospitalization: hospitalization that is not due to 
heart failure or other cardiovascular causes, as defined 
above 
 
Patients hospitalized with heart failure meeting these criteria 
should further be subclassified into:   
o Primary (cardiac related) heart failure: this may be due 
to any cardiac cause, including primary LV dysfunction 
with or without medication or dietary noncompliance, 
acute MI, arrhythmias, and worsening valve dysfunction 
o Secondary (non-cardiac related) heart failure: when a 
non-cardiac primary condition is present such as 
pneumonia, urinary tract infection, or renal failure, which 
results in fluid overload or myocardial failure. 
Note: only primary heart failure should be considered a valid 
criterion for heart failure hospitalization 
 
Implant procedure 
Placement of the investigational device in the tricuspid valve 
regurgitant orifice.  
Infection 
Known infection requiring intravenous antibiotics for other than 
prophylaxis, and/or extended hospitalization. 
INR 
International normalized ratio 
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KCCQ 
Kansas City Cardiomyopathy Questionnaire is a health-related 
quality-of-life measure for patients with congestive heart failure. 
LVEF 
Left ventricular ejection fraction 
MAE 
Major adverse event defined as cardiovascular mortality, 
myocardial infarction, new need for renal replacement therapy, 
severe bleeding, re-intervention and major access site and 
vascular complications 
Malfunction 
Refer to ISO 14155 definition 
Mortality 
See “Death” 
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Myocardial Infarction 
(MVARC) 
 
o Periprocedural MI (≤48 hours after index procedure 
procedure)*†:   
 
A. In patients with normal baseline CK-MB (or cTn):  
o The peak CK-MB measured within 48 h of the procedure 
rises to ≥10x the local laboratory ULN (Upper Limit of 
Normal) PLUS new ST-segment elevation or depression 
of ≥1 mm in ≥2 contiguous leads (measured 80 ms after 
the J-point) 
o The peak CK-MB measured within 48 h of the procedure 
rises to ≥5x ULN with new pathological Q waves in ≥2 
contiguous leads or new persistent LBBB 
o In the absence of CK-MB measurements and a normal 
baseline cTn, a cTn (I or T) level measured within 48 h of 
the PCI rises to ≥70x the local laboratory ULN PLUS new 
ST-segment elevation or depression of ≥1 mm in ≥2 
contiguous leads (measured 80 ms after the J-point) 
o The peak CK-MB measured within 48 h of the procedure 
rises to ≥35x ULN with new pathological Q waves in ≥2 
contiguous leads or new persistent LBBB. 
 
B. In patients with elevated baseline CK-MB (or cTn): The 
CK-MB (or cTn) rises by an absolute increment equal to 
those levels recommended above from the most recent 
pre-procedure level plus, new ECG changes as 
described. 
 
o Spontaneous MI (>48 hours after index procedure 
procedure):   
 
Detection of rise and/or fall of cardiac biomarkers 
(preferably cTn) with at least 1 value above the 99th 
percentile URL (or ULN in the absence of URL) together with 
at least 1 of the following: 
□ Symptoms of ischemia 
□ ECG changes indicative of new ischemia (new ST-
segment or T-wave changes or new LBBB) or new 
pathological Q waves in ≥2 contiguous leads 
□ Imaging evidence of a new loss of viable 
myocardium or new wall motion abnormality 
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o MI associated with sudden, unexpected cardiac 
death‡:  
 
Sudden cardiac death or cardiac arrest, often with 
symptoms suggestive of myocardial ischemia, and 
accompanied by presumably new ST-segment elevation or 
new LBBB and/or evidence of fresh thrombus by coronary 
angiography and/or at autopsy, but death occurs before 
blood samples could be obtained or at a time before the 
appearance of cardiac biomarkers in the blood 
 
o Pathological findings of an acute myocardial 
infarction‡ 
 
Note: 
 
The use of high sensitivity (hs)-troponins is recommended for 
diagnosis of Type II (spontaneous) MI, but has not been studied 
for assessment of periprocedural MI. Standard troponin assays 
are therefore recommended for evaluation of Type I MI 
 
Situations where MI is suspected must be carefully evaluated 
by taking into consideration past medical history, procedural 
specifics, renal function etc. It is known that cardiac procedures 
are associated with multiple confounding factors that 
contribute to myocardial damage 
 
*Periprocedural biomarker elevation >ULN not meeting the 
criteria for MI should be categorized as “myonecrosis not 
meeting MI criteria.”  
 
†Adapted from Moussa et al.  
 
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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.  They 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. 
Nonstructural 
Dysfunction 
Abnormality extrinsic to the repair device that results in valve 
dysfunction (stenosis, regurgitation or both)  
Pacemaker 
Dependency 
Continuous ventricular stimulation without any pacemaker 
inhibition by spontaneous cardiac activity determined during the 
last interrogation within 180 days. 
Patient  
A person with the disease (tricuspid regurgitation) being 
screened to participate or participating in this clinical study. 
Peripheral 
Thromboembolic 
Event 
See “Embolism” 
Pre-Existing Condition 
A pre-existing condition is one that was present prior to clinical 
study screening. 
Procedural Success 
Procedural success: device success with evidence of TR reduction 
as evidenced by a relative reduction in EROA of ≥ 30% from 
baseline to discharge and without the need for a surgical or 
percutaneous intervention prior to hospital discharge.  
Prosthesis 
An artificial substitute  
QoL 
Quality of Life 
Reintervention 
Any intervention (surgical or transcatheter) on the previously 
implanted study device (repair, alteration or replacement). 
Renal Failure 
See “Acute Kidney Injury (AKI)” 
Screen Failure  
A patient who has signed the consent but, does not fulfill 
enrollment criteria: does not meet the inclusion criteria or who 
meets at least one of the exclusion criteria. 
Serious Adverse 
Device Effect (SADE) 
Refer to ISO 14155 definition 
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Serious Adverse Event 
(SAE) 
(ISO 14155:2011) 
Adverse event that: 
1. led to death 
2. led to serious deterioration in the health of the patient that 
     either resulted in : 
a. a life-threatening illness or injury, or 
b. a permanent impairment of a body structure or a body  
function, or 
c. in-patient or prolonged hospitalization, or 
medical or surgical intervention to prevent life threatening 
illness or injury or permanent impairment to a body structure 
or a body function. 
3. led to fetal distress, fetal death or a congenital abnormality 
or birth defect (not anticipated in this study as pregnant 
women are excluded from the study) 
Severe Bleeding 
(MVARC) 
Severe bleeding is a major, extensive, life-threatening or fatal 
bleeding. 
SF-12 
A short survey with 12 questions that results in two scales of 
mental and physical functioning and overall health related 
quality of life. 
Six (6) MWT 
Six minute walk test 
Spacer Migration 
Anchor has not migrated from original implanted position, 
Spacer is no longer within the tricuspid valve (non-therapeutic) 
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Stroke/TIA 
(MVARC) 
Stroke 
1. Acute episode of a focal or global neurological deficit 
with at least one of the following:  
• Change in level of consciousness 
• Hemiplegia  
• Hemiparesis 
• Numbness 
• Sensory loss affecting one side of the body 
• Dysphasia or aphasia 
• Hemianopia 
• Amaurosis fugax 
• Other neurological signs or symptoms consistent with 
stroke 
 
2. Duration of symptoms: 
• A focal or global neurological deficit ≥ 24 hours 
• A focal or global neurological deficit < 24 hours if 
available neuroimaging indicates a new intracranial 
or subarachnoid hemorrhage (hemorrhagic stroke) 
or central nervous system infarction (ischemic 
stroke) 
• The neurological deficit results in death 
 
3. 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.* 
 
4. Confirmation of the diagnosis by at least one of the 
following:  
o Neurologist or neurosurgical specialist, or 
o Neuroimaging procedure (CT scan or brain MRI) 
o Non-neurologist physician (if neurologist is not 
available) 
o Clinical presentation alone 
 
Stroke etiology will be classified as: 
 
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• Ischemic: an acute symptomatic episode of focal 
cerebral, spinal, or retinal dysfunction caused by an 
infarction of the central nervous system tissue  
• Hemorrhagic: an acute episode of focal or global 
cerebral or spinal dysfunction caused by 
intraparenchymal, intraventricular, or subarachnoid 
hemorrhage 
• Undetermined: if there is insufficient information to 
allow categorization as ischemic or hemorrhagic 
 
Stroke severity  
 
• Disabling: mRS score of ≥ 2 at 90 days (or the last 
available clinical visit with evaluable data) AND an 
increase in ≥ 1 mRS category from an individual’s pre-
stroke baseline 
 
• Non-disabling: mRS score of < 2 at 90 days (or the last 
available clinical visit with evaluable data) or doesn’t 
result in an increase in ≥ 1 mRS category from pre-
stroke baseline  
 
It is recognized that an assessment of stroke is incomplete 
without an appropriate measurement of the disability resulting 
from the stroke, hence, mRS closest to 90 days post event** 
will be used to assess clinical disability using the following scale: 
 
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 
 
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CEC adjudicator will indicate if there was an increase of mRS 
since pre-stroke baseline, how much the mRS has increased, 
and the mRS total score closest to 90 days post Stroke.  
 
 
TIA 
 
Acute episode of a focal or global neurological deficit fulfilling 
the following criteria:  
 
1. Resulting in at least one of the following 
• Change in level of consciousness 
• Hemiplegia 
• Hemiparesis 
• Numbness 
• Sensory loss affecting one side of the body 
• Dysphasia or aphasia 
• Hemianopia 
• Amaurosis fugax 
• Other neurological signs or symptoms consistent with 
stroke 
 
2. Duration of deficit could be one of the following: 
• A focal or global neurological deficit < 24 hours  
• Any available neuroimaging does not demonstrate a 
new hemorrhage or infarct 
 
3. 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.* 
 
Notes:  
 
• If neurological event does not meet the definition of 
Stroke or TIA, the CEC adjudication will indicate that 
accordingly on the form.  
• *Patients with non-focal global encephalopathy will not 
be reported as a stroke without unequivocal evidence 
based upon neuroimaging studies. 
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• **Evaluation of stroke between 30 and 90 days is 
acceptable if 90-day follow-up not available 
#If a stroke is reported without evidence of confirmation of 
the diagnosis by one of these methods, the event may still 
be considered a stroke on the basis of the clinical 
presentation alone. 
Patient  
Refer to ISO 14155 definition 
Patient Withdrawal 
A patient who decides not to participate in the study after signing 
an informed consent form and being enrolled. 
Thromboembolic 
Event  
See “embolism” 
Thrombus  
(Device Thrombosis) 
An aggregation of platelet, fibrin, clotting factors, and other 
cellular elements exclusive of infection.  
 
Device thrombosis is defined as any thrombus in the absence of 
infection attached to or near the investigational device that 
interferes with function of the device.  An investigational device 
related thrombus may be confirmed by operation, autopsy, or 
diagnostically 
by 
such 
methods 
as 
echocardiography, 
angiocardiography, or magnetic resonance imaging. 
Transient Ischemic 
Attack (TIA) 
(MVARC) 
See “Stroke/TIA” 
 
Tricuspid 
Regurgitation 
Tricuspid Regurgitation (TR), tricuspid insufficiency or tricuspid 
incompetence describes a condition in which blood flow through 
the tricuspid valve flows in the incorrect direction during part of 
the cardiac cycle. 
Unanticipated 
Adverse Device Effect 
(UADE) 
(FDA) 
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 problems 
associated with a device that relates to the rights, safety, or 
welfare of patients. 
Valvular Leak  
 
(See Also 
“Nonstructural 
Dysfunction”)  
Any evidence of leakage of blood through the native valve 
leaflets and around the investigational device. Diagnosis of 
valvular leak may be obtained from echo; however definitive 
diagnosis is obtained at reoperation, explant, or autopsy.  
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Withdrawal by 
Investigator 
A patient who consents to participate in the study and is  
enrolled but is withdrawn by the Investigator.  
 
 
 
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19 APPENDIX A - SAMPLE INFORMED CONSENT FORM 
 
 
 
 
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