TRI-REPAIR: TrIcuspid Regurgitation RePAIr With CaRdioband Transcatheter System
Phase: NA
Conditions: Tricuspid Valve Insufficiency, Tricuspid Regurgitation, Tricuspid Valve Regurgitation, Cardiovascular Diseases, Heart Valve Diseases, Heart Diseases, Cardiac Valve Annuloplasty
Sponsor: Edwards Lifesciences



 
 
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- TR 
TRI-REPAIR 
Tricuspid Regurgitation Repair 
with Cardioband Transcatheter System 
Protocol ID TR1-1   
 
 
Rev. 05 - Date: 25 May 2017  
Sponsor: 
Valtech Cardio  
3 Ariel Sharon Ave. 
Or Yehuda 60376  
ISRAEL 
Tel:  +972-3-5335959 
Fax: +972-3-5335578 
Confidentiality Statement 
This document is confidential and is to be distributed for review only to investigators, potential investigators, 
consultants, study staff, and applicable independent ethics committees or institutional review boards.  The 
contents of this document shall not be disclosed to others without written authorization from Valtech Cardio 
Ltd., unless it is necessary to obtain informed consent from potential study participants. 

 
 
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Protocol Signatures 
Prior to participation in this study, the Principal Investigators must obtain written approval from his/her Ethics 
Committee, and provide a copy to the Sponsor, Valtech Cardio Ltd., or their authorized representatives, along 
with the Ethics Committee approved Informed Consent Form.   
 
The Principal Investigator must also: 
 
Conduct the study in accordance with the study protocol, the Investigator Agreement, the Declaration of 
Helsinki, Good Clinical Practices, international harmonized standards for clinical investigation of medical 
devices (ISO 14155:2011, Clinical investigation of medical devices for human subjects – Good clinical 
practices), the laws and regulations of the countries where the study will take place, indemnity / insurance 
requirements and any other applicable regulations.   
 
Agree to participate in an appropriate training program as part of the study initiation. 
 
Assure that informed consent is obtained from each subject prior to enrollment, using the Ethics 
Committee approved form.   
 
Assure that the study is not commenced until Ethics Committee approval has been obtained. 
 
Provide all required data and agree to source document verification of study data with subject’s medical 
records.   
 
Allow staff of the Sponsor and its authorized representatives, as well as representatives from regulatory 
agencies, to review, inspect and copy any documents pertaining to this clinical investigation.  
 
Complete and return all case report forms, study documentation, and relevant imaging assessments 
promptly to Sponsor and/or the designated core laboratory for data processing. 
The Principal Investigator (PI) may delegate one or more of the above functions to an associate or sub-
investigator.  The PI retains overall responsibility for proper conduct of the study. 
Investigators’ Signature  
I have read and understand the contents of the clinical protocol.  I agree to follow and abide by the guidelines 
set forth in this document.  
 
Principal Investigator ______________________________ 
 
Signature: 
_________________________________________ 
Date: ____________ 
 
Co-Principal Investigator (If applicable) ________________________ 
 
Signature: 
_________________________________________ 
Date: ____________ 
Sponsor Signature  
 
Sponsor Representative Name (print): ____________________________________________ 
 
Signature: 
_________________________________________ 
Date: ____________ 
 

 
 
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TABLE OF CONTENTS   
REVISION  HISTORY ................................................................................................................. 1 
1 
PROTOCOL SYNOPSIS ......................................................................................................... 8 
2 
LIST OF ABBREVIATIONS .................................................................................................. 13 
3 
INTRODUCTION ................................................................................................................... 14 
3.1 
TRICUSPID REGURGITATION: A "FORGOTTEN" PROBLEM ...................................................... 14 
3.2 
LIMITATIONS OF AVAILABLE TREATMENT ............................................................................. 17 
3.3 
TRICUSPID REPAIR WITH RING ANNULOPLASTY ................................................................... 17 
3.4 
TRICUSPID REGURGITATION IN THE CONTEXT OF MITRAL VALVE DISEASE ............................. 18 
3.5 
SIMILARITIES BETWEEN MITRAL AND TRICUSPID ................................................................. 19 
3.6 
TRANSCATHETER VALVE REPAIR........................................................................................ 20 
3.7 
SUMMARY OF CARDIOBAND FOR MITRAL REGURGITATION REPAIR CLINICAL RESULTS ........... 21 
4 
CARDIOBAND TR ADJUSTABLE ANNULOPLASTY SYSTEM .......................................... 25 
4.1 
INTENDED USE ................................................................................................................. 25 
4.2 
GENERAL DESCRIPTION ................................................................................................ 25 
4.2.1 CARDIOBAND IMPLANT .................................................................................................. 25 
4.3 
PRINCIPLES AND MODE OF OPERATION ............................................................................. 27 
4.4 
JUSTIFICATION OF THE CLINICAL INVESTIGATION ................................................................. 27 
5 
INVESTIGATION DESIGN & ENDPOINTS ........................................................................... 28 
5.1 
CLINICAL STUDY OVERVIEW .............................................................................................. 28 
5.2 
STUDY OBJECTIVES .......................................................................................................... 28 
5.3 
STUDY ENDPOINTS ........................................................................................................... 28 
5.4 
STUDY STOPPING CRITERIA .............................................................................................. 29 
5.5 
ANALYSIS OF DATA ........................................................... ERROR! BOOKMARK NOT DEFINED. 
6 
SUBJECT ENROLMENT ...................................................................................................... 31 
6.1 
INCLUSION CRITERIA ......................................................................................................... 31 
6.2 
EXCLUSION CRITERIA........................................................................................................ 31 
6.3 
CLINICAL SITE QUALIFICATION ........................................................................................... 32 
6.4 
ECHOCARDIOGRAPHIC IMAGING ........................................................................................ 32 
6.5 
SUBJECT WITHDRAWAL ..................................................................................................... 33 
6.6 
SCREENING FAILURE ........................................................................................................ 34 
7 
STUDY VISITS AND PROCEDURES ................................................................................... 34 
7.1 
UNSCHEDULED VISITS ...................................................................................................... 36 
8 
CARDIOBAND IMPLANT PROCEDURE .............................................................................. 36 
8.1 
CARDIOBAND SYSTEM PROCEDURE ................................................................................... 36 
9 
CLINICAL RISK BENEFIT EVALUATION ............................................................................ 37 

 
 
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9.1 
EXPECTED BENEFITS ........................................................................................................ 37 
9.2 
ANTICIPATED RISKS .......................................................................................................... 37 
9.3 
POTENTIAL RISKS AND ADVERSE EVENTS .......................................................................... 37 
9.4 
RISK/BENEFIT RATIO ......................................................................................................... 39 
10 ADVERSE EVENTS AND ADVERSE DEVICE EFFECTS .................................................... 39 
10.1 REPORTING REQUIREMENTS ............................................................................................. 39 
10.2 DEFINITIONS .................................................................................................................... 39 
10.3 REPORTING PROCEDURES ................................................................................................ 41 
10.4 ADVERSE EVENT TREATMENT AND FOLLOW-UP ................................................................... 41 
10.5 MONITORING OF ADVERSE EVENT DOCUMENTATION ........................................................... 42 
10.6 SPONSOR ASSESSMENT OF EVENTS AND SAFETY UPDATE ................................................... 42 
10.7 CLINICAL EVENTS COMMITTEE .......................................................................................... 43 
11 ETHICAL ASPECTS AND REGULATORY REQUIREMENTS ............................................. 43 
11.1 ETHICS COMMITTEE REVIEW AND APPROVAL ...................................................................... 44 
11.2 CLINICAL INVESTIGATION REGULATORY NOTIFICATIONS ....................................................... 44 
11.3 TRAINING REQUIREMENTS ................................................................................................ 44 
11.4 INVESTIGATOR RESPONSIBILITIES ...................................................................................... 45 
11.5 PATIENT INFORMATION AND INFORMED CONSENT ............................................................... 45 
11.6 INSURANCE ...................................................................................................................... 46 
11.7 PROTOCOL DEVIATIONS .................................................................................................... 47 
11.8 STUDY DOCUMENTATION AND RECORD KEEPING................................................................. 47 
11.9 REGULATORY DOCUMENTS ............................................................................................... 47 
11.10 SOURCE DOCUMENTS ....................................................................................................... 48 
11.11 RETENTION OF STUDY DOCUMENTS ................................................................................... 48 
11.12 CASE REPORT FORMS (CRF) ............................................................................................ 48 
11.13 INVESTIGATIONAL DEVICE ACCOUNTABILITY........................................................................ 49 
11.14 FINAL STUDY REPORT AND PUBLICATION POLICY ................................................................. 49 
12 STUDY MONITORING .......................................................................................................... 50 
12.1 GENERAL REQUIREMENTS................................................................................................. 50 
12.2 STUDY OVERSIGHT ........................................................................................................... 50 
12.3 DATA MANAGEMENT ......................................................................................................... 51 
12.4 DATA COLLECTION AND REVIEW ........................................................................................ 51 
13 SPONSOR DUTIES AND RESPONSIBILITIES .................................................................... 52 
13.1 ROLE OF THE SPONSOR.................................................................................................... 52 
13.2 STUDY SUSPENSION OR TERMINATION PROCEDURES .......................................................... 52 
13.3 SPONSOR STUDY FILES ..................................................................................................... 53 
14 REFERENCES ...................................................................................................................... 54 

 
 
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1 
PROTOCOL SYNOPSIS 
 
Background 
The Cardioband Transcatheter System (Cardioband) is a marketed 
system that was approved for treatment of secondary (functional) 
mitral regurgitation (FMR) (CE granted on September 2015). The 
Cardioband is an annuloplasty band that is similar to a surgical 
annuloplasty, however deployed on the beating heart through a 
transvenous approach. The CE mark study with 45 subjects has 
been completed and documented significant reduction of severity of 
MR and improvement in quality of life by MLHFQ, NYHA and 6-
minute walk test, in subjects with moderate to severe MR.  The aim 
of the current study is to evaluate the Cardioband annuloplasty 
system for repair the Tricuspid Regurgitation (TR). 
Sponsor 
Valtech Cardio LTD 
3 Ariel Sharon Ave. 
Or Yehuda 60376 Israel 
Tel:  +972-3-5335959 
Fax: +972-3-5335578 
Study Title 
TRI-REPAIR – Tricuspid Regurgitation Repair with Cardioband 
Transcatheter System 
Device 
The Cardioband Adjustable implant is delivered and anchored to the 
tricuspid valve annulus by a transfemoral delivery system. The 
Cardioband will be deployed along the Anterior and posterior 
annulus of the Tricuspid valve and will be adjusted under trans-
esophageal guidance on the beating heart. 
Indication for Use 
The treatment is for reconstruction and/or repair of pathological 
tricuspid valves. 
Study justification 
The current management of tricuspid regurgitation is either 
conservative (by medication) or by surgery, usually in concomitant 
with other valves repair or replacement. TR can worsen or appear 
late after successful mitral valve surgery which portends a poor 
prognosis. However, standard surgical approaches requiring 
cardiopulmonary bypass and especially second surgery have an 
excessive risk.  Thus, many patients are denied surgery because of 
unfavorable risk-benefit balance. Therefore, there is a need for novel 
devices enabling interventional cardiologists and cardiothoracic 
surgeons to perform tricuspid annuloplasty by transcatheter 
methods. Cardioband replicates established surgical techniques 
(e.g., annuloplasty) using transfemoral approach, without sutures 
and with adjusted on the beating heart.  Similar to the approved 
indication for mitral annuloplasty. The Cardioband system is 

 
 
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expected to allow for treatment of patients that would otherwise not 
undergo Tricuspid valve repair due to the invasiveness of current 
techniques. 
Study Design 
Prospective, single-arm, multi-center study. 
Objectives 
To assess the safety and technical success of the Cardioband 
system for the treatment of symptomatic chronic functional tricuspid 
regurgitation. 
Primary 
Safety 
Endpoint 
Overall rate of Major Serious Adverse Events (MSAEs)* and 
serious adverse device effects (SADE) until hospital discharge 
and at post-operative 30 days.  
* Death, myocardial infarction, cardiac tamponade, device related 
cardiac surgery, stroke 
Primary Technical 
Endpoint 
Successful access, deployment and positioning of the Cardioband 
device and septolateral reduction at intraprocedure and discharge. 
Secondary Endpoints 
 
 TR grade, EROA and Regurgitant Volume (by Echocardigraphy) 
 Tricuspid annular plane systolic excursion (TAPSE)  
 Technical success 
 NYHA classification 
 6-Minute Walk Distance (6MWD) 
 Kansas City Cardiomyopathy Questionnaire (KCCQ) 
 LVEF 
 LVEDVI 
 LVESVI 
 NT-pro BNP 
 Diuretic Therapy 
 GOT, GPT (ALT), and Bilirubin    
 BUN Creatinine clearance  
 Activity by wearable device 
Endpoints will be measured at discharge 1,6,12 and 24 months post 
procedure and will be compared to baseline 
Number of Subjects 
60 subjects 
Investigational Sites 
6 sites in Europe  
Inclusion Criteria 
1. Chronic functional tricuspid regurgitation (FTR) 2+ to 4+ on a 
scale of 4+ (moderate to severe)  with annular diameter ≥ 40 
mm with valve Systolic pulmonary pressure (sPAP) ≤ 
60mmHg 
2. ≥18 years old 

 
 
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3. New York Heart Association (NYHA) Class II-IVa 
4. Symptomatic despite Guideline Directed Medical Therapy 
(GDMT); at minimum patient on diuretic regimen 
5. LVEF ≥ 30% 
6. Patient is willing and able to comply with all specified study 
evaluations  
7. The Local Site Heart Team concur that surgery will not be 
offered as a treatment option 
8. Transfemoral access of the Cardioband is determined to be 
feasible 
Exclusion Criteria 
1. Aortic, mitral and/or pulmonic valve stenosis and/or   
      regurgitation ≥ moderate 
2. Severe uncontrolled hypertension (SBP ≥ 180 mmHg and/or 
DBP ≥ 110 mm Hg) 
3. Previous tricuspid valve repair or replacement 
4. Presence of trans-tricuspid pacemaker or defibrillator leads 
which  cause impingement of the tricuspid valve leaflet as 
evaluated by echocardiography.  
5. Active endocarditis 
6. MI or known unstable angina within the 30 days prior to the 
index procedure 
7. Any PCI or transcatheter valvular intervention within 30 days 
prior to the index procedure  
8. Hemodynamic instability or on IV inotropes 
9. Cerebrovascular Accident (CVA) within the past 6 months 
10. Subject is on chronic dialysis 
11. Anemia (Hb < 9 g/L) not corrected by transfusion 
12. Bleeding disorders or hypercoaguable state 
13. Active peptic ulcer or active gastrointestinal (GI) bleeding 
14. Contraindication to anticoagulants 
15. Known allergy to stainless steel, nickel, and/or polyester   
16. Pregnant or lactating; or female of childbearing potential with 
a positive pregnancy test 24 hours before any study-related 
radiation exposure 
17. In the judgment of the Investigator, co-morbid condition(s) that 
could limit the subject’s ability to participate in the study, 
including compliance with follow-up requirements, or that 
could impact the scientific integrity of the study 
18. Life expectancy of less than 12 months 
19. Impaired judgment and/or is undergoing emergency treatment 
20. 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 

 
 
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21. intra-cardiac masses, thrombi or vegetations 
22. Patients with cardiac cachexia 
23. Subjects in whom transesophageal echocardiography is 
contraindicated 
24. Known hypersensitivity or contraindication to procedural 
medications which cannot be adequately managed medically 
25. Untreated 
clinically 
significant 
CAD 
requiring 
revascularization  
26. Echocardiographic evidence of severe right ventricular 
dysfunction 
27. Any coronary or endovascular surgery, within 3 months prior 
to procedure 
 
Procedure 
The system will be delivered percutaneously via the femoral vein. 
The procedure will be guided by fluoroscopy and trans-esophageal / 
intracardiac echocardiography 
Follow-Up Schedule 
1 month: 30 ± 14 days 
6 Months: 180 ± 30 days 
12 Months: 365 ± 30 days 
24 Months: 730 ± 30 days 
Subjects in whom no devices are implanted will be followed for 6 
months. 
Follow Up Evaluations 
 
Key Pre-Implantation Procedures: 
1. History and Physical 
2. TTE , TEE and/or CT angiography and/or MRI 
3. 6 minute walk test  
4. KCCQ 
Key Post-Procedure Procedures: 
1. Serial AE assessment, history, and physical at 30 days, 6 
months, 12 months, 24 months) 
2. Serial TTEs (30 days, 6 months, 12 months, 24 months) 
3. Cardiac MRI at 6 months (optional) 
4. 6 minute walk tests (30 days, 6 months, 12 months, 24 
months) 
5. KCCQ 
Clinical Event 
Committee 
An independent Clinical Event Committee will adjudicate all Serious 
Adverse events. 
First subject in 
Last subject in 
 
 
 
 
 
 

 
 
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Last follow-up 
 
 
 

 
 
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2 
LIST OF ABBREVIATIONS 
ACC/AHA 
American College of Cardiology/ 
American Heart Association 
KCCQ 
Kansas City Cardiomyopathy 
Questionnaire 
CABG 
Coronary artery bypass graft 
LV 
Left Ventricle 
CAD 
Coronary artery disease 
LVEDV 
Left Ventricle End Diastolic Volume 
CEC 
Clinical Events Committee 
LVESV 
Left Ventricle End Systolic Volume 
CHF 
Congestive Heart Failure 
6MWT 
6 minute walk test 
CPB 
Cardiopulmonary bypass 
MI 
Myocardial infarction 
CRT 
Cardiac Resynchronization Therapy 
MLHFQ 
Minnesota living with heart failure 
questionnaire 
EC 
Ethics Committee 
MR 
Mitral regurgitation 
eCRF 
Electronic Case Report Form 
MRI 
Magnetic Resonance Imaging 
EF 
Ejection fraction 
MSCT 
Multislice computed tomography 
FDA 
Food and Drug Administration 
NYHA 
New York Heart Association 
GCP 
Good Clinical Practice 
TEE 
Transesophageal echocardiography 
GLP 
Good Laboratory Practices 
TTE 
Transthoracic echocardiography 
GMP 
Good Manufacturing  Practices 
TR 
Tricuspid Regurgitation 
ICH 
International Conference on 
Harmonization 
TV 
Tricuspid Valve 
IFU 
Instructions for use 
 
 
 

 
 
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3 
INTRODUCTION 
3.1 
Tricuspid regurgitation: a "forgotten" problem 
Tricuspid Regurgitation (TR) is a disorder of the heart in which the Tricuspid valve, that separates 
the right atrium from the right ventricle, does not close properly during systole. TR is a frequent life 
threatening condition associated with heart failure and poor prognosis. 
TR is a poor prognostic factor. Presence of significant TR is indecently associated with about two 
fold increase in the risk, in heart failure patients(1,2) Topilsky et al in a study involved 353 patients 
with isolated TR have showed that the outcome of isolated severe functional TR, independently of 
other cardiovascular or comorbid conditions, is characterized by excess mortality and excess cardiac 
events (3) 
Significant TR is estimated to occur in more than 1.6 million people in the United States and less 
<1% of patients with moderate or severe TR undergo surgery annually (3,4) despite a 1-year mortality 
rate of 36.1% ( Figure 1) vast majority of cases are managed conservatively due to the still evolving 
understanding of the disease Figure 1(5,6,7). 
 
Figure 1: Kaplan-Meier survival curve for patients with Tricuspid regurgitation (TR). Survival is 
significantly worth in patients with moderate and severe TR. 
 
It is not surprising then, that the both the ESC and AHA have changed their guidelines in recent 
years and urge physicians to treat TR at an earlier stage in patients with concomitant left side valve 
pathology requiring surgery (Figure 2) (8,9) Recent reports also show a decrease in mortality in 
patients treated for isolated TR at an early stage, before they suffer NYHA IV cardiac failure (3,11) 
Appropriate patient selection and proper timing for repair or replacement are crucial for optimal 
outcome, but objective criteria for clinical decision-making remain poorly defined. 
 

 
 
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Figure 2: Comparison of European and American Guidelines for treatment of tricuspid  
regurgitation (8, 9) 
 
Tricuspid regurgitation etiology has been categorized to primary (Organic) and secondary or 
functional (FTR) (Table 1). The main etiologies of primary TR that accounts for only 8–10% of all 
severe TRs, include rheumatic disease, congenital abnormalities, endocarditis and trauma (8, 9). 
There are also a variety of metabolic, enzymatic, or pharmacologic abnormalities associated with 
TR (12). Functional TR (FTR) is defined as regurgitation without any identifiable structural damage to 
the Tricuspid valve, leaflets, or chords. FTR usually occurs in the presence of pulmonary artery 
hypertension from any cause (most commonly from elevated left sided pressures), RV enlargement, 
and tricuspid annular dilatation (13, 14). With the decreasing prevalence of rheumatic disease, FTR is 
proportionally more common and accounts for most of observed cases of severe TR (14, 15). 
 
 
 

 
 
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Table 1: Ethology of tricuspid regurgitation 
 
 
Dilation of the TA occurs mainly in its anterior and posterior sides (Figure 3) corresponding to the 
free wall of the right ventricle, while the dilation of the septal segment is limited because of its close 
anatomical relationship with the fibrous skeleton of the heart (15). 
 
 
 
 
 
 
Figure 3: anatomy of the tricuspid valve  
A) Normal tricuspid valve. (B) Asymmetric dilation and deformation of the tricuspid annulus leading to 
tricuspid regurgitation. Adapted from Shinn and Schaff (16). 
Primary tricuspid valve disease  
 
Congenital  
Ebstein's anomaly  
Congenital cleft valve 
Congenital tricuspid stenosis 
Tricuspid atresia  
Acquired  
 
Rheumatic  
Infective endocarditis  
Degenerative. Tricuspid valve prolapse  
Carcinoid heart disease 
Toxic (eg, Phen-Fen or methysergide valvulopathy) 
Tumors (eg, fibroelastoma, myxoma) 
Trauma  
Latrogenic (eg, pacemaker lead trauma, radiation injury, 
biopsy instrument)  
Secondary or functional tricuspid 
valve disease 
 
 
Right ventricular dilatation (eg, atrial septal defect, 
Pulmonary regurgitation) 
Right ventricular hypertension (eg, pulmonary 
hypertension, pulmonary stenosis)  
Right ventricular dysfunction (eg, cardiomyopathy, 
myocarditis) 
Segmental right ventricular dysfunction (eg, ischemia or 
infarction, endomyocardial fibrosis, arrhythmogenic  right 
ventricular dysplasia) 
Chronic atrial fibrillation (asymmetric tethering leads to 
eccentric jet)  

 
 
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Tricuspid regurgitation is also a predictor of poor outcome in patients undergoing balloon mitral 
valvotomy for mitral stenosis. Patients with pre-procedural severe TR have more severe MV disease, 
higher pulmonary vascular resistance, a smaller increase in MV area after valvotomy, as well as 
poorer outcome: lower overall survival, more heart failure, and need for repeat valvotomy or MVR 
(Figure 5). 
 
Figure 5: Event free survival after balloon mitral valvotomy by TR severity Events were defined as 
death, New York Heart Association functional class III or IV, MV surgery, or repeat mitral valve 
balloon valvotomy (n = 318). Patients with severe tricuspid regurgitation (TR) had significantly worse 
event-free survival compared with patients with mild TR. Reprinted, with permission, from Sagie et 
al 37). 
patients with severe TR after MVR undergoing isolated TR surgery usually have a poor outcome 
with high perioperative mortality that might reach 50%, but it was usually reported between 11% and 
20% (38, 39, 40, 41, 16) The great risk with TV surgery, especially in prior cardiotomy patients, leaves these 
patients under-treated. Percutaneous intervention that entails low procedural risks together with the 
possibility of fixing or replacing the vale could indeed have an important role in the treatment of this 
large group of patients.  
3.5 
Similarities between Mitral and Tricuspid 
The mitral and Tricuspid valves or the atrioventricular valves are similar both in structure and in 
function; both controls the flow of blood from the atria into the ventricles. During systole, the valvar 
leaflets, which bulge toward the atrium, stay pressed together throughout the contraction, and 
therefore do not prolapse. During diastole, when the ventricles are relaxing, the atrioventricular 
valves open to allow the flow of blood to fill the ventricles. The atrioventricular valvar complex has 
four main components, namely the annulus, leaflets, tendinous cords, and papillary muscles (142). 
Carpentier described the mitral valve as consisting of two opposing leaflets while the tricuspid valve 
normally possesses three distinct leaflets, which traditionally are described as being anterior, 
posterior, and septal (Figure 6). It is natural then, that they will also share the pathogenesis of 
regurgitation or insufficiency. For example, in patients with pulmonary hypertension (functional TR), 
the right ventricle becomes globular, leading to tethering of tricuspid leaflets, similar to functional 
mitral regurgitation. Regurgitation of flow across the atrioventricular valves can further be sub-

 
 
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classified into functional and degenerative. Degenerative (primary) incompetence is considered to 
be a disease of the valve itself while functional regurgitation is usually considered to be a disease of 
the ventricles. The gold standard treatment for atrioventricular valves incompetence is by surgical 
repair or replacement. Surgical treatment for pathologies of the atrioventricular valves has been 
shown to improve overall survival when compared to medical therapy alone, particularly in the case 
of degenerative mitral regurgitation 43). In case of repair, the surgeon will usually place an 
annuloplasty ring to reduce and maintain the overall circumference of the valve.  
 
Figure 6: The atreoventricular valves leaflet. The mitral valve on the left and the tricuspid valve on the 
right. (Adopted from Carpentier 1976) 
Due to the invasive nature of surgery, and the common co-morbidities associated with this 
population, there are significantly number of patients that often biases against surgical intervention, 
particularly for those who are in excessive high risk for surgery and therefore transcatheter therapies 
are required to meet the broad clinical needs.  
3.6 
Transcatheter valve repair 
In the past decade, transcatheter aortic valve replacement (TAVR) has widely adopted intervention 
that replaced surgical AVR 4445). The success of TAVR has stimulated attempts at transcatheter mitral 
valve replacement (TMVR) for percutaneous treatment of mitral regurgitation (MR). This has proven 
to be far more complex than TAVR, however there are several devices that are approved for Mitral 
valve repair; The Mitraclip device (Mitraclip, Abbott Vascular, Santa Rosa, California) is available for 
use in the EU and lately received U.S. Food and Drug Administration approval. The Cardioband 
device (Valtech cardio LTD, Or Yehuda, Israel) was also recently approved in the EU (46, 47). First-in-
human testing has begun also for transcatheter Mitral valve replacement (48). The next attention 
therefore is the "forgotten valve", the tricuspid valve.  
Today, there is no designated system for transcutaneous repair of TR approved for clinical use. Few 
have reported their experience with Valve in Valve repair, using devices designed for TAVR inserted 
into a prosthetic tricuspid valve via a the SVC an49d IVC 49). 
Lauren Et al. reported the successful implantation of a self-expandable tubular stent tailored to the 
dimensions of the inferior vena cava at the landing zone with significant reduction in IVC pressures 
(50). Similar attempt was done with the Sapien XT valve. It is important to notice that such and 
intervention leads to ventricularisation of the RV and cause severe deterioration for patients with 
severe RV heart failure. A first in human report of the use of the Mitralign system (Mitralign 
Tewksbury, Massachusetts) in a trans jugular approach to treat TR was recently published using a 
technique that eventually causes bi-cuspidalisation of TV valve and reduction of annulus dimension 
(51).As Cardioband is the only commercially available direct annuloplasty device that mimic the 
surgical approach with transcatheter techniques, it is natural to test the use of Cardioband for 
Tricuspid annuloplasty. 

 
 
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The Cardioband Transcatheter System (Valtech cardio LTD) is currently indicated for the treatment 
of secondary (functional) mitral regurgitation (FMR). The Cardioband is direct annuloplasty 
transcatheter system, deployed on the beating heart through a transvenous approach. The implant 
is deployed along the posterior annulus of the mitral valve and is adjusted under trans-esophageal 
guidance on the beating heart. A CE mark study has been completed and documented reduction of 
severity of MR and improvement in functional tests in subjects with moderate to severe MR (4646). As   
the Cardioband delivery system enables catheter movement in few dimensions the same delivery 
system can be used to implant the same annuloplasty band in the right side for repair of Tricuspid 
regurgitation. Catheter used directions are demonstrated in Figure 7. 
   
 
 
 
 
 
 
Figure 7: Cardioband system can be used for Mitral and Tricuspid annuloplasty 
 
 
 
 
 
   
  
 
 
 
 
 
 
 
 
 
   
 
Mitral 
Tricuspid 

 
 
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4 
CARDIOBAND TR ADJUSTABLE ANNULOPLASTY SYSTEM  
4.1 
Intended Use  
Cardioband TR reconstruction System is indicated for the reconstruction and/or repair of pathological 
Tricuspid valves. 
4.2 
General Description 
The Cardioband Transfemoral (TF) Delivery system is designed to introduce and deploy the 
Cardioband implant in the appropriate location along the tricuspid annulus and then adjust the 
Cardioband implant in order to narrow the annulus.  
4.2.1 Cardioband Implant 
Cardioband implant is an adjustable annuloplasty band designed for valve repair by transfemoral 
procedure.  
The Cardioband implant is deployed and fixated along the anterior - posterior annulus and is then 
adjusted to remodel the tricuspid valve. 
The Cardioband implant consists of a contraction wire and polyester fabric covering that are attached 
to an Adjustment mechanism.  The polyester covering is marked with radio-opaque (RO) markers at 

 
 
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set distances along the implant. The Implant guidewire is connected to the adjustment mechanism 
of each implant in order to enable over-the-wire adjustment after implantation.  
4.2.2 The Cardioband Adjustable System 
The Cardioband System consists of the following main parts: 
1. Cardioband implant (Figure 8, Figure 9) 
 
2. Cardioband Delivery System (Figure 10) is a transfemoral delivery system, designed to 
introduce and deploy the Cardioband implant in the appropriate location along the annulus 
and then adjust the Cardioband implant. The Delivery system consists of the following main 
parts: 
a. Transfemoral Steerable Sheath (TSS) 
b. Dilator, used for introduction of the TSS to the femoral vein and left atrium. 
c. Implant Delivery System (IDS), which includes a Guide Catheter (GC) and an Implant 
Catheter. 
d. Size Adjustment Tool.  
 
3. Anchor Drives  
 
 
For additional details, please refer to Instructions for Use 
. 
 

 
 
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4.4 
Justification of the clinical investigation 
Currently the best option for Tricuspid regurgitation is repairing the valve with an “annuloplasty ring” 
in an open heart surgery, usually in concomitant with mitral or other valve repair. Occasionally 
however the patients are in too high risk for operation, the risk of reoperation is extremely high and 
has been reported to reach up to 20% mortality (32, 33, 3435). Cardioband proposes a non-invasive, fully 
adjustable, direct annuloplasty repair. The evidence presented above indicates that Cardioband 
1) lower surgical risks of operation and re-operation by using established transfemoral 
techniques 
2)  Enable a significant reduction of the mitral septo-lateral annulus, and therefore MR 
reduction 
3) Enable fine-tuning of the repair by adjusting the device size on a beating heart per the 
patient anatomy 
Cardioband for treatment of Tricuspid repair targets an unmet clinical need, in that the device 
is based on established surgical devices, and is expected to allow for treatment of patients 
that would otherwise not undergo Tricuspid valve repair due to the invasiveness of current 
techniques. Given these potential benefits, and the favourable safety profile of the 
Cardioband device for MR repair there is ample justification for a prospective investigation 
focusing on the clinical performance and safety of the Cardioband system for tricuspid 
regurgitation valve repair.  

 
 
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5 
INVESTIGATION DESIGN & ENDPOINTS 
5.1 
Clinical Study Overview  
This clinical investigation is a single arm, multi-center, prospective study with intra-patient 
comparisons. 
Candidates for Cardioband TR treatment are symptomatic patients with functional tricuspid valve 
repair. Patients are selected upon clinical conditions and severity of TR. Anatomical feasibility is 
assessed by Echocardiography and/or other exams (such as CT and angiography) according to the 
site common practice. Patients will be screened and enrolled according to the study inclusion and 
exclusion criteria. 
Patients will undergo tricuspid valve repair with Cardioband implanted via transcatheter procedure 
under Transoesophageal / Intracardiac echocardiography (TEE/ICE) and fluoroscopy guidance. 
Post-procedure clinical care will be performed according to standard management of valve repair; 
Clinical follow-up including standard post-procedural management of surgical valve repair and 
Transthoracic Echo (TTE) assessment of the degree of Tricuspid regurgitation will be obtained at 
hospital discharge, 30 days, 6, 12 and 24 months post-index procedure. 
As the follow up at 30 days is of most importance in terms of the patient’s safety: The first 3 patients 
will have to complete 30 days follow up before the recruitment of additional patients. In related to the 
first 3 patients, recruitment will continue in case of elongated hospitalization or complications that 
are unrelated to the study device as will be judge by the study clinical event committee. 
  
5.2 
Study objectives 
The objective of this study is to assess the safety and technical success of the Cardioband system 
for the treatment of symptomatic chronic functional tricuspid regurgitation. 
5.3 
Study Endpoints 
5.3.1 Primary endpoints 
 
Safety: 
Overall rate of Major Serious Adverse Events (MSAEs)* and serious adverse device effects 
(SADE) until hospital discharge and at post-operative 30 days.  
* Death, myocardial infarction, cardiac tamponade, device related cardiac surgery, stroke. 
 
Technical Success:  
Successful access, deployment and positioning of the Cardioband device and septolateral reduction 
at intra-procedure and discharge 
 

 
 
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5.3.2 Secondary endpoints 
 
TR grade, EROA and Regurgitant Volume (by Echocardigraphy) 
 
Tricuspid annular plane systolic excursion (TAPSE)  
 
Technical success 
 
NYHA classification 
 
6-Minute Walk Distance (6MWD) 
 
Kansas City Cardiomyopathy Questionnaire (KCCQ) 
 
LVEF 
 
LVEDVI 
 
LVESVI 
 
NT-pro BNP 
 
Diuretic Therapy 
 
GOT, GPT (ALT), and Bilirubin    
 
BUN Creatinine clearance  
 
Activity by wearable device 
Endpoints will be measured at discharge, 1, 6, 12 and 24 months post procedure and will be 
compared to baseline 
5.4 
Study Stopping Criteria 
The study will be stopped if in the first 5 patients up to 2 patients will experience one of the following 
serious adverse device effects: 
 
 
Death 
 
Need for operation/band replacement 
 
The same stopping criteria will be applied to the total study population as it follows: 
 
 
Device-related SADE and study stopping criteria 
 
SADE 
5 pts 
10 pts 
20 
30 
Death 
or 
need 
for 
emergency 
operation 
2 
2 
3 
3 
 
 
Events will be assessed by an independent clinical event committee (CEC). 
 
In case of early termination of the investigation all the relevant parties will be promptly informed by 
the sponsor with a report of the reasons of this early termination.  

 
 
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deviation, minimum, median and maximum. Categorical variables will be summarized by a count 
and percentage. If statistical tests will be done the significance level will be equal to or lower than 
5%. Nominal p-values will be presented. Where confidence limits are appropriate, the confidence 
level will be 95%. 
Baseline demographic and other baseline characteristics, together with safety analyses will be 
performed on all subjects.  
 
The numbers of subjects who entered and completed each visit of the study will be provided, as 
well as the reasons for all discontinuations, grouped by major reason (e.g., lost to follow-up, 
adverse event, etc.). A list of discontinued subjects, protocol deviations, and subjects excluded 
from the efficacy analysis will be provided.  
Descriptive statistics will be provided for the efficacy and safety outcome results.  
The analysis of all adverse events will include incidence tables and incidence tables by severity, 
relationship to treatment and baseline parameters. Serious adverse events will be listed and 
discussed individually.
 
 
6 
 SUBJECT ENROLMENT 
The inclusion and exclusion criteria listed below must be used for the purpose of enrolling patients 
into this clinical investigation.  
6.1 
Inclusion criteria 
Patients who participate in this study must meet all of the following inclusion criteria: 
1. chronic functional tricuspid regurgitation (FTR) 2+ to 4+ on a scale of 4+ (moderate to severe) 
with annular diameter ≥ 40 mm with valve Systolic pulmonary pressure (sPAP) ≤ 60mmHg 
2. ≥18 years old 
3. New York Heart Association (NYHA) Class II-IVa 
4. Symptomatic despite Guideline Directed Medical Therapy (GDMT); at minimum patient on 
diuretic regimen 
5. LVEF ≥ 30% 
6. Patient is willing and able to comply with all specified study evaluations 
7. The Local Site Heart Team concur that surgery will not be offered as a treatment option 
8. Transfemoral access of the Cardioband is determined to be feasible 
6.2 
 Exclusion criteria 
Patients who fulfill any of the following criteria may not participate in this study. 
1. Aortic, mitral and/or pulmonic valve stenosis and/or regurgitation ≥ moderate 
2. Severe uncontrolled hypertension (SBP ≥ 180 mmHg and/or DBP ≥ 110 mm Hg) 
3. Previous tricuspid valve repair or replacement 
4. Presence of trans-tricuspid pacemaker or defibrillator leads which   which  cause 
impingement of the tricuspid valve leaflet as evaluated by echocardiography.  

 
 
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5. Active endocarditis 
6. MI or known unstable angina within the 30 days prior to the index procedure 
7. Any PCI or transcatheter valvular intervention within 30 days prior to the index procedure 
8. Hemodynamic instability or on IV inotropes 
9. Cerebrovascular Accident (CVA) within the past 6 months 
10. Subject is on chronic dialysis 
11. Anemia (Hb < 9 g/L) not corrected by transfusion 
12. Bleeding disorders or hypercoaguable state 
13. Active peptic ulcer or active gastrointestinal (GI) bleeding 
14. Contraindication to anticoagulants 
15. Known allergy to stainless steel, nickel, and/or polyester   
16. Pregnant or lactating; or female of childbearing potential with a positive pregnancy test 24 
hours before any study-related radiation exposure 
17. In the judgment of the Investigator, co-morbid condition(s) that could limit the subject’s 
ability to participate in the study, including compliance with follow-up requirements, or that 
could impact the scientific integrity of the study 
18. Life expectancy of less than 12 months 
19. Impaired judgment and/or is undergoing emergency treatment 
20. 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 
21. intra-cardiac masses, thrombi or vegetations  
22. Patients with cardiac cachexia 
23. Subjects in whom transesophageal echocardiography is contraindicated 
24. Known hypersensitivity or contraindication to procedural medications which cannot be 
adequately managed medically 
25. Untreated clinically significant CAD requiring revascularization 
26. Echocardiographic evidence of severe right ventricular dysfunction 
27. Any coronary or endovascular surgery, within 3 months prior to procedure 
 
 
 
 
 
  
6.4 
Echocardiographic imaging 
Echocardiographic data will be collected from the TEE and TTE images for the corelab interpretation 
of the degree of TR reduction and adverse events, if any. A physician or sonographer familiar with 
valvular heart disease and experienced in performing echocardiograms should perform each 
assessment.  
 
 

 
 
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6.5 
Subject withdrawal 
6.5.1 Withdrawal  
Subjects may withdraw from the study at any time for any reason, according to the terms of the 
Informed Consent document, which includes continuation of clinical study follow-up whenever 
possible, and ongoing medical care as appropriate. Subjects may also be withdrawn from the study 
at any time at the discretion of the investigator.  
It should be understood that an excessive rate of withdrawals could render the study difficult to 
interpret. Hence, unnecessary withdrawal of subjects should be avoided. Should a subject withdraw 
or is withdrawn, every effort must be made to complete and report the observations as thoroughly 
as possible. If possible, in case of withdrawal, permission for yearly study telephone follow up to 
assess long-term outcomes and safety will be obtained from the subject.  
6.5.2 Procedures for handling withdrawal 
Subjects who withdraw or are withdrawn from the study should: 
 
Have the reason(s) for their withdrawal recorded (if possible). 
 
May be seen by an investigator and all final assessments should be performed and recorded. 
 
Be asked about the presence of any AEs. If an ongoing AE if present, the patient should be 
followed up until satisfactory clinical resolution of the event is achieved. 
 
If a subject is withdrawn, Valtech monitor should be informed as soon as possible by the site. One 
additional subject will be enrolled for each subject withdrawn (or died) for any reason before the 
primary endpoint period completed. 
 
For each patient with missing significant data for the primary endpoint, such as data regarding 
performance (access, deployment and positioning) of the Cardioband device, and/ or missing an 
Echocardiography, an additional patient will be recruited. 
6.5.3 Lost to follow up 
If a subject does not appear for a follow-up visit and cannot be contacted for collecting follow-up 
information the primary physician will be contacted and will be asked about the subject’s health 
condition. At least 3 attempts should be made to contact the subject through all available routes 
attempt to contact the patient should be recorded.    If there is no contact with the patients and/or 
primary physician - he/she will be considered ‘lost to follow up’. One additional subject may be 
enrolled for each lost to follow up before the primary endpoint period completed. 
 

 
 
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6.6 
Screening failure  
A screening failure will be defined as patient who fulfilled the theoretical eligibility criteria, and was 
intended to treat, however Cardioband was not be implanted due to new information detected at 
the time of procedure, preventing the implantation. A screening failure will be followed until 
discharge from hospital.  
7 
STUDY VISITS AND PROCEDURES 
The study will commence following institutional medical ethics committee and regional competent 
authority approval. Study evaluation continues until 24 months of follow up post implantation has 
been obtained on all available participating subjects.  
Screening of patients will be performed according to the hospital standard screening for tricuspid 
valve repair and replacement.  In addition, patients will be screened for their suitability for Cardioband 
therapy. A central eligibility committee will be established to determine final enrolment of patients 
across all investigational sites. The eligibility committee will include at least a Heart Failure specialist, 
and an Echocardiography specialist. Patients will give a written consent for health information 
release prior to screening process. The treatment procedure will be performed according to the 
instructions outlined in the current approved IFU.  
Data will be collected at the following time points (as expected in the course of a surgical treatment): 
baseline, procedure, discharge and clinical follow-up at 30 days, 6 months, 12 months and 24 
months from index procedure. Data from any other additional time points may be collected and 
analyzed if available. 
The procedures associated with each study visit are outlined and summarized in Table 4.  
 

 
 
 
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Procedure 
Screening 
Baseline 
Implantation  
Discharge 
30 days 
6, 12, 24 
months 
Visit Number 
-1 
0 
1 
2 
3 
4 
Range 
- 1 month 
- 1 month 
0 
NA 
-1 wk/+ 2 wks 
+/- 1 month 
Data release  Consent 
X 
 
 
 
 
 
Study informed consent 
 
X 
 
 
 
 
Demographics 
  
X 
 
 
 
 
Wearable data watch 
 
X 
X 
X 
X 
X 
Medical History  
  
X 
 
 
 
 
Routine Blood tests 
  
X 
 
X 
X 
X 
Pregnancy test (if applicable) 
 
X 
 
 
 
 
General Clinical State 
 
X 
 
X 
X 
X 
Adverse Events 
 
X 
X 
X 
X 
X 
Medica ion Profile 
 
X 
 
X 
X 
X 
Tricuspid Regurgitation Assessment by TTE 
X 
X 
 
X 
X 
X 
Tricuspid Regurgitation Assessment by TEE 
 
X 
X 
 
 
 
Tricuspid valve anatomy (by Echo and/or CT) 
X 
 
 
 
 
 
Coronary Angiography (within the past 12 months, optional) 
X 
 
 
 
 
 
Cardiac MRI (optional) 
X 
 
 
 
 
X 
6-minute walk test 
 
X 
 
 
X 
X 
QoL questionnaire (KCCQ) 
 
X 
 
 
X 
X 
NYHA Functional Class 
 
X 
 
 
X 
X 
Cardioband Implantation 
 
 
X 
 
 
 
Table 4: Schedule of Visits and Procedures

 
 
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7.1 
Unscheduled Visits 
An unscheduled visit will be any visit to the clinical site other than the specific visits requested in the 
protocol. The Investigator or trained and qualified investigational staff will perform all procedures 
necessary to evaluate the study participant at these visits, and record the visit in the subject’s chart. 
At the very least, safety information such as occurrence of adverse events will be recorded during 
the unscheduled visit. The Principal Investigator must be notified by the subject immediately of any 
unscheduled visits to any medical facilities during the study period. (Subjects will be instructed to 
report).  
8 
CARDIOBAND IMPLANT PROCEDURE  
 
Cardioband is implanted by transfemoral procedure. 
 
 
 
8.1 
Cardioband system procedure 
Prior to the procedure, subjects must be evaluated to determine eligibility for transfemoral venous 
access. Absolute or relative contraindications to transfemoral procedures will be evaluated by the 
principal investigator and or interventional cardiologist.    
 
The Cardioband system procedure is performed under echocardiography and fluoroscopy guidance. 
The procedure summarized in the following steps: 
1. The subject is prepared as per standard practice for transvenous catheterization. 
2. Cardioband implant size is selected according to the tricuspid annulus size measured 
preoperatively and the implant is mounted as specified in the IFU. 
3. The transfemoral steerable sheath (TSS) with the Dilator are inserted through the femoral 
vein, the tip of the TSS is steered into the RA under echo guidance. 
4. After removing the dilator and guidewire, the implant delivery system is inserted. 
5. The system is navigated to the anterior part of the annulus, proximal to the aortic root. The 
first anchor is placed. 
6.  The system is navigated to the next anchoring site while deploying the implant fabric along 
the anterior and posterior annulus.  
7. Implant deployment and anchoring is continued until the Cardioband implant reaches the 
coronary sinus opening.  
8. The implant is then disconnected from the implant catheter. The Implant Delivery system is 
removed.  
9. The Size adjustment tool (SAT) is then inserted over the implant guidewire and engaged with 
the implant. 
10. Adjustment is performed using the SAT, under echocardiography guidance.   
11. After achieving the desired result, the SAT is detached. 
12. The System is removed upon completion. 
 

 
 
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Additional details on procedures, contraindications, and risks are provided in the device 
Instructions for Use. 
9 
CLINICAL RISK BENEFIT EVALUATION 
9.1 
Expected benefits 
Tricuspid regurgitation is a significant disease with one year mortality 36.1 %( 3, 4), but less <1% of 
patients with moderate or severe TR undergo surgery. The vast majority of cases are managed 
conservatively due to the excessive risk of open heart surgery (56, 7). 
Thus, there is an unmet clinical need for devices enabling to perform a valve repair in a non-invasive 
fashion and without cardiopulmonary bypass. 
Cardioband was proved to llower the surgical risks by using established transfemoral techniques; 
Based on established annuloplasty surgical devices. Cardioband was showed to reduce the Mitral 
septo-lateral annular dimension and therefore reduce the MR. MR Reduction accompanied with 
improvement of the NYHA stage, 6 minute walk test and MLHFQ questionnaire.  
Although there are no guaranteed benefits from participation in this study the Cardioband System is 
expected to allow for treatment of patients that would otherwise not undergo Tricuspid valve repair 
due to the invasiveness of current techniques. In addition Cardioband enable fine-tuning of the repair 
by adjusting the device size on a beating heart. 
Given these benefits showed for mitral valve repair, there is ample justification for a prospective 
investigation focusing on the clinical performance and safety of the Cardioband system for treatment 
of the Tricuspid valve as well. 
9.2 
Anticipated risks 
The potential risks associated with Cardioband can be divided into three categories: First, there are 
the risks associated with transcatheter repair procedures the patient population (high risk for surgery) 
and anaesthesia. These risks are expected to be similar to risks that were reported for mitral valve 
repair by transcatheter devices in similar populations (e.g. Carillion, mitraclip, etc.).  Second, there 
are the risks uniquely associated with annuloplasty procedures using ring/band which similarly are 
not expected to significantly differ between marketed systems and the Cardioband System. Third, 
there are risks specifically associated with the Cardioband procedure. The latter are also expected 
to be similar to those reported for those reported for the use of Cardioband for mitral repair. 
 
A risk analysis according to ISO 14971 Application of Risk Management to Medical Devices has 
been conducted.  
9.3 
Potential Risks and Adverse Events 
The following ANTICIPATED EVENTS have been identified as possible complications of the 
Cardioband TF procedure:  
1. Risks associated with the procedure and administration of anaesthesia including but 
not limited to  the following: Death; Stroke/ transient ischemic attack; Haemolysis; Heart 
block; Perforation or damage of vessels, myocardium or valvular structures; Pericardial 

 
 
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effusion/cardiac tamponade; Haematoma; Blood loss requiring transfusion; Infection 
including endocarditis and septicaemia; Arrhythmia;  Air embolus; Thromboembolism; Fever; 
Hypertension/hypotension; Allergic dye reaction; Allergic  Anaesthesia reactions; Aneurysm; 
Atrial Septal defect requiring intervention; Arterio-venous fistula; Cardiac Arrest; 
Coagulopathy; Deep Venous thrombus (DVT); Dyspnoea; Edema; Esophagus irritation; 
Esophagus perforation or stricture; Gastrointestinal bleeding or infarct; Hematoma; 
Haemolysis; Haemorrhage requiring transfusion; Infection and pain in insertion or incision 
site; Lymphatic complication; Mesenteric ischemia; Multi-system failure; Myocardial 
infarction;  Nausea/vomiting; Peripheral ischemia; Prolonged angina; Prolonged ventilation; 
Pulmonary Congestion; Pulmonary thrombo-embolism; Renal insufficiency; Respiratory 
failure/atelectasis/pneumonia; septicaemia; Urinary tract infection; Vascular trauma, 
dissection or occlusion; Vessel spasm; vessel perforation or laceration; worsening heart 
failure . 
2. Potential risks specifically associated with the use of annuloplasty rings/bands 
include, but may not be limited to the following: reoperation and explants; residual or 
recurrent or worsening  regurgitation requiring intervention; haemolysis; conduction system 
disturbances including atrioventricular block; endocarditis; low cardiac output; right heart 
failure; failure or degeneration of the natural valvular apparatus due to progression of 
disease; 
inadequate 
repair 
of 
the 
valvular 
and 
subvalvular 
structure; 
detachment/dislodgment (partial or full) of the annuloplasy ring/band from its site of 
attachment; migration or malposition; malfunction of the ring/band due to distortion or fracture 
at the implant or physical or chemical deterioration of band components; bleeding 
complications related to use of anticoagulant therapy; prosthesis thrombosis; infection.  
3.  Risks specifically associated with the Cardioband, in addition to the general risks of 
annuloplasty, include, but may not be limited to the following :Conversion to standard 
valve surgery; Failure to deliver the band to the intended site; tissue damage or vascular 
injury due to anchor insertion; Unsuccessful adjustment of the band; Tissue damage from 
insertion and removal of system components; Cardioband components embolism; Partial 
device dehiscence (anchor detachment) and disturbances to the conduction system. 
 
The potential for the occurrence of device dehiscence, device mal-position, and residual or recurrent 
regurgitation requiring intervention is expected to be similar to that seen for Mitral valve repair with 
the Cardioband device. Clinical study for MR repair  have demonstrated that Cardioband procedure 
is relatively safe and can reliably result in a significant reduction of the annular septo-lateral 
dimension and MR, and functional improvement in patients with FMR 46). 
 
As with any device undergoing clinical investigation, there may be unforeseeable risks, which are 
not known at this time. Medical and/or surgical intervention may be required to correct clinical 
complications associated with the device procedure. 

 
 
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9.4 
Risk/benefit ratio 
Cardioband proposes a less invasive, fully adjustable, direct annuloplasty for tricuspid regurgitation 
repair, and as presented above targets an unmet clinical need for Tricuspid repair in a patients that 
are at high risk for surgery. 
Cardioband had shown to enable a “surgical annuloplasty” for mitral regurgitation repair through a 
percutaneous approach. 
 
 
 
 
 
 
 
 
 
   
 
 
 The benefit–risk profile is expected to be similar for the 
tricuspid regurgitation annuloplasty repair and will be rigorously addressed in the clinical trial.   
10 ADVERSE EVENTS AND ADVERSE DEVICE EFFECTS 
10.1 Reporting requirements 
Timely and complete reporting of Adverse Events (AE) and safety assessments allows: 
 
 
Protection of safety and study subjects. 
 
Greater understanding of the overall safety profile of the study treatment. 
 
Appropriate modification of study protocols and improvement in study design and 
procedures. 
 
Adherence to regulatory requirements. 
 
The definitions and reporting requirements adopted in this study are derived from the current 
International standard on clinical investigations: EN ISO 14155:2011 Clinical Investigations of 
medical devices for human subjects – Good Clinical Practices. 
10.2 Definitions 
 
Based on ISO 14155:2011 
 
Adverse event 
Any untoward medical occurrence, unintended disease or injury or any untoward clinical signs 
(including an abnormal laboratory finding) in subjects, users or other persons whether or not related 
to the investigational medical device. This includes events related to the procedures involved. 
 
This definition does not imply that there is a relationship between the adverse event and the device 
under investigation. An AE can therefore be any unfavorable and unintended sign, symptom, 

 
 
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laboratory observations or disease temporally associated with the use of the investigational product, 
whether or not related to the investigational product. 
 
The following should be reported as AE: 
 
Untoward medical conditions or signs or symptoms that were absent before starting study 
treatment. 
 
Untoward medical conditions or signs or symptoms present before starting study treatment 
and worsen (increase severity or frequency) after starting study treatment. 
 
Abnormal laboratory values or tests which are clinically significant. 
 
Clinical signs or symptoms that require therapy.  
 
Adverse device effect (ADE) 
Adverse event related to the use of an investigational medical device. This includes any adverse 
event resulting from insufficiencies or inadequacies in the instructions for use, the deployment, the 
implantation, the installation, the operation, or any malfunction of the investigational medical device. 
This includes any event that is a result of a use error or intentional misuse. 
 
Therefore, some adverse device effects may be related to device deficiencies, defined as follows: 
 
Device deficiency 
Inadequacy of a medical device related to its identity, quality, durability, reliability, safety or 
performance. Device deficiencies include malfunctions, misuse or use errors and inadequate 
labeling. 
 
- 
Device Malfunction: failure of an investigational medical device to perform in accordance with 
its intended purpose when used in accordance with the instructions for use or clinical 
investigation protocol. 
- 
Use Error: act or omission of an act by the user that results in a different medical device 
response than intended by the manufacturer or expected by the user. Use error includes 
slips, lapses, and mistakes. An unexpected physiological response of the patient is not by 
itself considered use error. 
 
A device deficiency shall be reported as AE or SAE according to the AE and SAE definitions. 
 
Device deficiencies that did not lead to an adverse event but could have led to a medical occurrence 
if: 
- 
A suitable action had not been taken, 
- 
intervention had not been made 
- 
circumstances had been less fortunate, 
- 
Shall be reported as well as an adverse event. 
 
Serious adverse event (SAE) 
Adverse event that 
a) Led to a death, 
b) Led to a serious deterioration in the health of the subject that either 

 
 
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1) Resulted in a life-threatening illness or injury, or 
2) Resulted in a permanent impairment of a body structure or a body function, or 
3) Required in-patient hospitalization or prolongation of existing hospitalization, or 
4) Resulted in medical or surgical intervention to prevent life threatening illness or injury or 
permanent impairment to a body structure or a body function. 
c) Led to foetal distress, foetal death or a congenital abnormality or birth defect 
 
NOTE: A planned hospitalization for pre-existing condition, or a procedure required by the CIP, 
without a serious deterioration in health, is not considered to be a serious adverse event. 
 
Unanticipated serious adverse device effect (USADE) 
Serious adverse device effect which by its nature, incidence, severity or outcome has not been 
Identified in the current version of the risk analysis report.  
NOTE: Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, 
severity or outcome has been identified in the risk analysis report. 
10.3  Reporting procedures 
Adverse event and adverse device effect information will be collected throughout the study. The 
investigator or research coordinator will record these events on the CRF's. The event, date of onset, 
severity, duration, and relationship to the device will be recorded. Any adverse event will be 
monitored until it is adequately resolved or stabilized. 
 
The investigator has the responsibility to report adverse events as they occur: 
 
 
The Ethics Committee must be informed of any serious adverse device effect. 
 
Valtech and the monitor must be informed of any adverse event without undue delay.  
 
All serious adverse events must be reported by completing a serious adverse event eCRF 
form as soon as of knowledge of the event. An automatic notification will be generated to 
Valtech and to the monitor upon the issue of such eCRF. Investigator should not wait to 
receive additional information to fully document the SAE, and should start the completion of 
the electronic form as soon as possible. The report of SAE should be followed by a full written 
report detailing relevant aspects of the SAE in question. Where applicable, information from 
relevant medical records and autopsy reports should be obtained. 
 
Other adverse events must be reported as soon as possible.  
10.3.1 Adverse Events Reporting Requirements in Germany 
In 
Germany, 
events 
will 
be 
reported 
in 
accordance 
with 
the 
“Medizinprodukte-
Sicherheitsplanverordnung” (MPSV).  
According to MPSV § 3 Nr.5 and 6, serious adverse events occurring during clinical investigations 
must be notified by the Sponsor and Investigator. 
The investigator will report to the sponsor within 24 hours of having information of an event occurred. 

 
 
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The sponsor’s reporting to BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte, the Federal 
Institute for Drugs and Medical Devices) as per regulation, will be performed immediately of the 
sponsor becoming knowledge of the occurrence of the SAE. 
 
1. For SAEs occurring in Germany, where a causal relationship between the SAE and the 
investigational medical device, the study or the study procedure cannot be excluded reporting 
will be made using the current SAE Report Form provided by BfArM. 
 
2. For SAEs occurring in other countries, where the clinical trial is performed and where a causal 
relationship between the SAE and the investigational medical device, the study or the study 
procedure cannot be excluded reporting will be made using the MEDDEV Form / Summary 
table. 
 
3. For all SAEs occurred where a causal relationship between the SAE and the investigational 
medical device can be excluded reporting to BfArM will be made on a quarterly basis by 
sending the MEDDEV Form. 
 
10.4 Adverse event treatment and follow-up 
Treatment of any AE is at the discretion of the investigator. Investigators must follow-up subjects 
with AE until the event has resolved (subject recovered) or until the condition has stabilized. 
Otherwise, appropriate medical care must be arranged for the subject. Abnormal test results should 
be repeated until return to baseline or acceptable levels. 
10.5  Monitoring of adverse event documentation 
During the monitoring visit, the monitor must perform the following verification activities: 
 
 
Confirmation of the accuracy of subject information supplied by the investigator concerning 
the seriousness of the event and causal relationship to the device; 
 
Ensuring that the appropriate adverse event CRFs have been completed by the site 
personnel; 
 
Verification of whether or not the investigator has followed established reporting procedures 
and, if required, has reported the event to Valtech and/or the EC, as appropriate. 
 
Confirmation that copies of EC reports and correspondence are maintained in the Site 
Regulatory Binder. 
 
For any negative change in subject test results, clinical status, or treatment (e.g., increased dose of 
diuretic, reduction in ejection fraction), the monitor must ensure that the corresponding AE has been 
documented. If a reportable AE is discovered that has not been reported, the Monitor must 
immediately initiate the proper reporting procedures in collaboration with the investigator, as defined 
by applicable regulatory requirements. If the change is not associated with an AE, the reason for the 
change must be appropriately explained on the appropriate CRF or narrative form.  
Any problems identified during these activities should be documented in writing and notified to 
Valtech. 
10.6 Sponsor assessment of events and safety update 
Sponsor representatives for vigilance notifications are identified in the Table below: 

 
 
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Valtech representative responsible 
for vigilance notifications 
 
 
 
  
 
 
 
Valtech European Authorized 
Representative 
 
 
 
 
 
 
 
 
 
Upon notification of adverse events, Valtech will initiate and complete a review and evaluation of the 
event within time frames that will maintain reporting compliance with applicable regulatory agencies.  
 
If insufficient information is available to reach a definitive diagnosis, Valtech will instruct the monitor 
responsible for the site to contact the site to request additional confirmatory information. The hospital 
discharge letter is usually the most informative document, which should contain a complete summary 
of the event, the results of diagnostic tests, whether surgery was performed and its outcome, the 
subject’s post-operative course, discharge, post-discharge treatment and follow-up, if any. If the 
outcome is death, an autopsy report must be requested. 
Upon review of AE data (including seriousness, frequency of occurrence and statistical significance) 
within Valtech if study termination is required due to an unreasonable risk or significant occurrence 
of risk to human subjects, the study will be terminated. 
10.7 Clinical Events Committee 
All Serious adverse events will be reviewed by an independent Clinical event Committee (CEC) for 
adjudication of the event relation to the study device or procedure. Major SAEs and SAEs that are 
related or possibly related to device or procedure will be reviewed by all CEC members, other 
SAEs will be reviewed by the CEC chairperson. 
11  ETHICAL ASPECTS AND REGULATORY REQUIREMENTS 
This study will be conducted in conformity with the ethical principles set forth by the Declaration of 
Helsinki, Good Clinical Practice (GCP) principles, international harmonized standards for clinical 
investigation of medical devices (ISO 14155:2011, Clinical investigation of medical devices for 
human subjects – Good clinical practices), the laws and regulations of the countries where the study 
will take place, and indemnity / insurance requirements. 
 
In addition, for this study Valtech has chosen to voluntarily comply with United States requirements, 
including those related to sponsor responsibilities (21 CFR 812.40), selection of investigators (21 

 
 
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CFR 812.43), monitoring (21 CFR 812.46), and any other applicable requirement for the purpose of 
facilitating acceptance of data in support of US regulatory submissions. 
11.1  Ethics Committee review and approval 
This investigational plan and the informed consent must be reviewed and approved by the 
appropriate Ethics Committee where the trial will be conducted before enrolment of subjects. 
Changes to the investigational plan that may increase the risk or present new risks to the subject, or 
that may adversely affect the validity of the trial, must be approved in writing by Valtech and the 
Ethics Committee. 
 
Prior to the subject enrolment, a signed copy of the Ethics Committee approval form or a signed 
copy of the Ethics Committee approval letter addressed to the investigator must be submitted to 
Valtech certifying this approval. Investigators are responsible for submitting and obtaining initial and 
continuing review of the trial by their Ethics Committee with the recurrence of at least once a year. 
 
All correspondence with the Ethics Committee should be filed in the Investigator’s Study File and a 
copy forwarded to Valtech and the site monitor. 
11.2  Clinical investigation regulatory notifications 
All necessary arrangements for the registration and approval of this study with the appropriate 
regulatory authorities will be undertaken by Valtech. As appropriate, the assigned submit 
amendments in the Investigational Plan to the appropriate Competent Authority and investigators to 
obtain Ethics Committee re-approval. Depending upon applicable national regulations and 
requirements, Valtech will submit the required Competent Authority reports, including: unanticipated 
adverse device effects, withdrawal of Ethics Committee approval, current investigator list, annual 
progress reports, recall information, final reports, and investigational plan deviations, where 
appropriate. 
Valtech Cardio Ltd. will report all reportable Serious Adverse Events to the Competent Authorities in 
accordance with European Medical Devices directives, the MEDDEV 2.7/3 and all applicable 
national regulations. 
 
Valtech will be represented in Europe by: 
 
 
 
 
 
 
11.3 Training Requirements 
Prior to investigation site activation, Valtech will provide study training relevant and pertinent to the 
involvement of personnel conducting study activities, investigator responsibilities, as well as device 
training. 

 
 
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11.4  Investigator responsibilities 
The selected investigators will provide written agreement to the following sponsor requests: 
 
 
To adapt the clinical routine if required by the protocol and local procedures to comply with 
the standardization required for the study; 
 
To comply with Good Clinical Practice, FDA Regulations and/ or ISO 14155:2011 for the 
conduct of clinical investigations of medical devices; 
 
To collect clinical data as outlined in this protocol and complete all relevant documentation 
(such as the case report form) in a legible and timely condition; 
 
To permit authorized sponsor representatives, monitors and auditors to inspect all records 
pertaining to the trial. 
 
The principal investigator will be required to submit curriculum vitae for participating medical team. 
Participating medical team will attend an education session to familiarize themselves with the 
protocol and GCP before the initiation of the study. 
11.5  Patient information and informed consent 
Informed consent is mandatory and must be obtained from all subjects and/or their legal 
representatives as per local regulations, prior to their participation in the study. The investigator must 
inform every subject in details about the nature of the study, its purpose, the treatments, those 
aspects of the study that are experimental, the procedures involved including all invasive procedures 
and the discomfort it may entail, the possible risks including to an embryo, foetus or nursing infant 
when applicable, the reasonably expected benefits, the expected duration and the approximate 
number of subjects involved and the subject’s responsibilities. 
 
The patient will also give his written consent for health information release, i.e. screening informed 
consent, in order to determine if the patient is a potential candidate for the device. 
 
Study subjects must additionally be informed that: 
 
 
Participation in this study is voluntary and that he/she may withdraw from this study at any 
time for any reason and that that withdrawal of consent will not affect his/her subsequent 
medical treatment or relationship with the treating physicians. 
 
Notification will be provided in a timely manner and in a written form if information becomes 
available that can significantly affect their future health and medical care. 
 
Alternative procedures or treatment that may be available and the important potential benefits 
and risks of these available procedures or treatments. 

 
 
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 
Any compensation for additional costs and/or injury caused to a subject attributable to 
participation in the study. 
 
Financial expenses, if any, to the subject for participating in the study as well as prorated 
payments, if any, to the subject for participating in the study. 
 
Any foreseeable circumstances and/or reasons under which the subject’s participation in the 
study may be determined. 
 
The person(s) to contact for further information regarding the study and whom to contact in 
the event of study related injury. 
 
Written consent will be obtained from each subject to be involved in the study. According to the 
Declaration of Helsinki, including legally incompetent patients is not recommended and as such is 
not allowed in the study. Potential study subject and/or his/her guardian should be given the 
opportunity to ask questions and time for consideration. 
 
A blank copy of the informed consent form approved by the Ethics Committee must be maintained 
in the Investigator’s study file. The original of each subject’s signed consent form must be filed by 
the investigator in the Subject CRF Binder, and a signed copy of the patient information and informed 
consent form must be given to each subject. 
11.5.1  Confidentiality and subject data protection 
All information and data concerning subjects or their participation in this trial will be considered 
confidential. 
Only those working on Valtech’s behalf, the independent Ethics Committee and regulatory authorities 
will have access to subject medical records and other study documents for verification of study 
procedures and data without violating the confidentiality of the subject. All data used in the analysis 
and reporting of this evaluation will not bear identifiable reference to the subjects.  
 
The investigator must assure that the subject’s anonymity will be maintained and that the 
confidentiality of records and documents that could identify subjects will be protected, respecting the 
privacy of and confidentiality rules in accordance with applicable regulatory requirements.  
 
 
Subjects must be identified only by their assigned study number in the CRFs and other 
records and documents submitted to Valtech, the monitor, and other authorized parties. 
 
The investigator will keep a Subject Identification List with complete identification information 
(full name, hospital ID if applicable and study ID) on each subject. This list will be kept at the 
investigational site solely.  
 
Documents not for submission to Valtech, such as subject’s written informed consent, should 
be maintained by the investigator in strict confidence. 
 
The subject should also be informed about the use of his/her health information collected during the 
study (study data). This information will be provided to the patient in the patient informed consent.  
11.6  Insurance 
For any injuries which can be traced to the study, subjects participating in the study are covered by 
insurance policies, as required by regulation for clinical studies. An product liability insurance policy 

 
 
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taken out by Valtech will cover liability for possible injury to the subject, provided the investigator and 
his/her staff have followed the instruction of sponsor in accordance with this protocol and any 
amendments thereto, that the investigational product administered to the subject in this study have 
been supplied by sponsor and that the investigator and his/her staff have in general performed this 
study in accordance with scientific practice and currently acceptable techniques and know how. 
11.7  Protocol deviations 
A deviation is defined in the ISO14155 standard as an instance of failure to follow, intentionally or 
unintentionally, the requirements of the CIP. The principle investigator shall document and explain 
any deviation from the approved CIP that occurred during the course of the clinical investigation. 
The investigator should not deviate from the investigational plan without the prior written approval of 
Valtech, except in medical emergencies or in unforeseen, isolated instances where minor changes 
are made that will not increase the subject’s risk or affect the validity of the investigation.  
Prior approval from the EC shall be obtained if the deviation affects subject's rights, safety and well-
being, or the scientific integrity of the clinical investigation; 
Under emergency circumstances, deviations from the CIP to protect the rights, safety and well-being 
of human subjects may proceed without prior approval of the sponsor and the EC. Such deviations 
shall be documented and reported to the sponsor and the EC as soon as possible. 
 All deviations will be documented and explained, regardless the reason for the deviation.  All 
deviations, regardless of their reason, will be reported to Valtech via a Study Deviation CRF (one 
CRF for each deviation). Valtech will assess the significance of all deviations and evaluate the need 
to take subsequent action (e.g. amending the Clinical Investigation Plan or terminating the 
investigation). When relevant, this shall be reported to the appropriate regulatory bodies. 
Deviations will be monitored on routine visits and will be summarized in monitoring reports as well 
as at the final study report.   
The sponsor shall consider terminating or suspending the participation of a particular investigation 
site or investigator in the clinical investigation if monitoring or auditing identifies serious or repeated 
deviations on the part of an investigator. 
11.8  Study documentation and record keeping 
The investigators must maintain adequate and accurate records to document the conduct of the 
study and substantiate the study data. These documents include those required by applicable 
regulations, and the subjects’ source documents, as described below. 
11.9  Regulatory documents 
Regulatory documents are those documents that individually and collectively permit evaluation of 
the study compliance with applicable regulations and the quality of the data produced. These 
documents include: 
 
1. Signed protocol and amendments 
2. Sample CRFs 
3. EC Approval letter 
4. Informed consent form 
5. CV of participating study team 
6. Correspondences with EC and sponsor  

 
 
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7. Interim reports to EC 
8. Investigational product accountability and shipping records 
9. Site signature (delegation) log 
10. Monitor visit log 
11. Other appropriate documents in accordance with GCP guidelines 
 
These documents will be filed in an Investigator File provided by Valtech. This file shall be used to 
facilitate and ensure filing of all relevant regulatory documents during and after the study. The 
investigator will be responsible for keeping the Investigator’s Study File updated and ensuring that 
all required documents are filed. The file will be inspected during monitoring visits. 
11.10  Source documents 
Source documents are original hospital records, clinical charts, screening log, subject identification 
list/enrolment log, original laboratory report, memoranda, pharmacy dispensing records, recorded 
data from automated instruments, transcriptions certified after verification as being accurate, 
microfiches, photographic negatives, microfilm, magnetic or electronic media, x-rays, subject’s files, 
and records kept at pharmacy, at the laboratories and medico-technical departments involved in the 
study. The investigator must maintain source documents for each subject in the study. All information 
recorded on the CRFs must be traceable to these source documents. 
11.11  Retention of study documents 
The investigator shall arrange for the retention of all study documents and records, including subject 
records, CRFs, drug inventory/accountability log, signed informed consent forms and the subject 
identification list for at least the number of years required by the local regulations after completion or 
discontinuation of the study. 
If the investigator moves or retires, he/she must nominate someone in writing to be responsible for 
archiving. Archived data may be held in electronic records, provided that a back-up exists and a hard 
copy can be obtained from it if required. 
If the investigator cannot guarantee this archiving requirement at the study site for any or all of the 
documents, special arrangements must be made with sponsor or Research Center to store these in 
a sealed container(s) outside of the site so that they can be returned sealed to the investigator in 
case of regulatory audit. 
Study records are to be discarded only upon notification by Valtech. If audits are required, the 
Principal Investigator shall allow access to the original medical records and provide all requested 
information. 
The study physicians should contact Valtech before the destruction of any records and reports 
pertaining to the study to ensure they no longer need to be retained. In addition, Valtech should be 
notified if the study physician plans to leave the institution. 
11.12  Case report forms (CRF) 
The site will record all information in an Electronic Data Capture (EDC) system, i.e. eCRF.  The 
EDC system used is validated software, and complies with CRF filling requirements, including audit 
trail and signature validation. Further information may be found in this document, section 12.5 – 
Data capture.  
  

 
 
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11.12.1 
Completion of CRFs 
It is the responsibility of the investigator to ensure that CRFs are legible and completely filled in to 
the EDC system, in a timely manner. 
 
An investigator or any personnel signature authorized by the investigator is required to personally 
sign each CRF on the appropriate pages to verify that the investigator has reviewed and concurs 
with the recorded data. No other person is permitted to sign for the investigator. The signature must 
be made at the time that the CRF is reviewed by the investigator signing the CRF.  
11.12.2 
CRF transmittal and retention 
The EDC system is protected by user and password. Data collected via eCRF will be retained by 
Valtech for at least the number of years required by the local regulations after completion or 
discontinuation of the study. 
 
11.12.3 
CRF review and data clarification 
The monitor (responsible CRA) will review the CRFs for completeness and accuracy at site or in-
house. In addition to the monitor's queries, the EDC system shall generate automatic queries 
according to predefined edit checks. Errors detected or suspected will require clarification and/or 
correction. Any data correction must be approved by the investigator. Wherever possible the 
investigator should assist in clarification or correction of errors detected within a timely manner. 
11.13  Investigational device accountability 
The Valtech devices to be used during this study will be supplied by Valtech. Investigational products 
should be maintained under adequate security by the investigator. Until the Valtech system is 
implanted, the system and its accessories should be stored at room temperature and protected from 
freezing, moisture and excessive heat. Required conditions for storing investigational product will 
also be printed on the label. The investigator or designee must maintain current and accurate record 
of the receipt, inventory and dispensing, including shipping invoices (if applicable) of all study 
supplies. Investigational product Accountability Log will be made available to facilitate inventory 
control. Accountability logs are subject to inspection by authorized parties at any time. Upon 
completion or termination of the study, unused investigational product must be returned to the 
sponsor. 
 
 
 
 
 
  
 
 
 
 
 

 
 
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12 STUDY MONITORING 
12.1  General requirements 
Valtech or its designees will conduct investigational site monitoring to ensure that all investigators 
are in compliance with the investigational plan and the Investigator’s Agreement. The monitors will 
verify source documentation against completed eCRF's and resolve any discrepancies. Monitors 
and Valtech will evaluate circumstances where an investigator deviates from the investigational plan. 
 
Valtech retains the right to remove either the investigator or the investigational site from the study. 
Valtech will fulfill its responsibilities in collecting and tracking data forms and instituting quality control 
measures for the data entry verification and trial compliance. Valtech will review significant new 
information including unanticipated adverse events and ensure that such information is provided to 
the Competent Authorities, investigators and to all reviewing Ethics Committees. 
12.2  Study oversight 
Primary data collection based on source-documented hospital chart reviews will be performed by 
the Valtech personnel or its designee monitor at each clinical site. Electronic case report forms will 
be completed in an expedited fashion. 
 
Each site will be visited regularly to ensure that the study is conducted in full compliance with all 
applicable regulations and the investigational plan. A pre-study meeting will be held with each 
potential investigational site in order to inform the prospective investigator and staff concerning 
features of the investigational device, investigation plan, applicable regulations and requirements, 
and expectations of the study, including the number and time frame for subject enrolment, subject 
selection, informed consent, required clinical data and record keeping. 
 
The prospective investigational site will be evaluated to ensure that it has an adequate subject base 
and can provide sufficient staff and documentation support to conduct the study properly. 
 
The Valtech study monitor will maintain personal contacts with the investigator and staff throughout 
the study by telephone, mail, e-mail, and on-site visits. The monitor will compile and file an 
observation report at each visit. Monitoring is intended to ensure continued protocol compliance, 
adequate subject enrolment, accurate data reporting, and adequate accounting of the investigational 
device. 

 
 
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Upon closure of the study at an investigational site, the study monitor will make a final onsite visit. 
The purpose of this visit is to collect all outstanding study documents, ensure that the investigator’s 
files are accurate and complete, review record retention requirements with the investigator, make a 
final accounting of all study supplies shipped to the investigator, provide for appropriate disposition 
of any remaining supplies, and ensure that all applicable requirements for the study are met. The 
observations and actions made at this visit will be documented as a final report for investigators and 
Valtech’s acceptance. 
 
12.3  Data management 
The sponsor agrees to be responsible of the verification that the trial is conducted implementing and 
maintaining quality assurance and quality control systems with written SOPs to ensure that the trials 
are conducted and data are generated, documented (recorded), and reported in compliance with the 
protocol, GCP, and the applicable federal, state and local laws, rules and regulations and guidelines 
relating to the conduct of the clinical trial. 
 
12.4  Data collection and review 
The investigator, or an individual designated by the investigator, is responsible for recording all data 
from the trial on the eCRF's supplied by Valtech.  
 
Valtech personnel or its designee will review completed eCRF’s at the investigational site at regular 
intervals throughout the investigation. To this end, the investigator must permit inspection of the 
investigation files and subject CRF's by such representatives and/or responsible governmental 
agencies. 
All eCRF’s will be tracked at Valtech and missing or unclear data will be requested as necessary 
throughout the investigation. Valtech or the monitor will request additional documentation, such as 
physician and/or laboratory procedure notes, in the event that complications or malfunctions are 
observed and reported. 
 
12.5 Data capture 
An Electronic Data Capture (EDC) system will be used for this study (EDC2go by Genae, a CRO 
and Data company based in Belgium and in the US). EDC2go is a software based CRF, designed 
to be FDA 21 CFR Part 11 compliant to collect data electronically. The system allows validation of 
data in terms of completeness accuracy. Each deviation from required fields, such as missing data, 
out of range data, or inappropriate data, will generate an automatic query, for the site to address.  
The system is compliant with FDA 21 CFR Part 11; meaning it is secured, and users are obliged to 
have their own password-protected username. Each data entry is registered and a complete audit 
trail is available at all times.  
A query will be generated when:  
1. A validation rule is not followed – generated automatically by the EDC system, or  

 
 
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2. During a monitoring visit, when there is inconsistency with the source documents - Manually 
by the monitor.  
The queries will remain open in the EDC system, until the designated site staff answer the question. 
The monitor will then be alerted of a new available answer, and only following re-monitoring, if the 
answer is sufficient, the query will be closed.  
Upon study completion, all data will be collected, and all queries will be answered, the data will be 
extracted and forwarded to an expert statistician for analysis. The data collected will be incorporated 
into the final report of this clinical study.  
13 SPONSOR DUTIES AND RESPONSIBILITIES 
13.1  Role of the Sponsor 
As the sponsor of this clinical study, Valtech has the overall responsibility for the conduct of the 
investigation. Valtech will have certain direct responsibilities and will delegate other responsibilities.  
 
The general duties of Valtech consist in submitting the clinical investigation notification to National 
Competent Authorities, obtaining Ethics Committee approvals prior to patient's enrollment, selecting 
qualified investigators, ensuring proper investigational site monitoring, and ensuring that informed 
consent is obtained. Valtech will prepare written progress reports and a final report, as required. 
 
Valtech will select qualified investigators; ship devices only to qualified participating investigators, 
obtain a signed Investigator’s Agreement, and provide the investigators with the information 
necessary to conduct the study. 
 
Valtech or its designees will conduct investigational site monitoring to ensure that all investigators 
are in compliance with the investigational plan and the Investigator’s Agreement. The monitors will 
verify source documentation against completed eCRF's and resolve any discrepancies. Monitors 
and Valtech will evaluate circumstances where an investigator deviates from the investigational plan. 
Valtech retains the right to remove either the investigator or the investigational site from the study. 
13.2  Study suspension or termination procedures 
Valtech reserves the right to terminate this study and remove all study materials from the study site 
at any time. The study may be suspended or terminated for any of the following reasons: 
 
 
It becomes apparent that subject enrolment is unsatisfactory with respect to quality or 
quantity 
 
Data recording is inaccurate and/or incomplete 
 
Violation or deviations from the signed protocol 
 
The incidence and/or severity of adverse events in this or in other studies indicate a potential 
health hazard caused by the treatment under study. 
 
Should a determination be made that the study should be suspended or terminated at one or all 
sites, then: 

 
 
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1. Enrolment shall be suspended or terminated at one or all the sites 
2. Currently enrolled subjects will be followed according to the protocol, which may be amended 
to accommodate study suspension or termination 
3. Valtech shall promptly inform the investigators and Ethics Committees of the suspension or 
termination and the reasons for it. 
 
Should Valtech decide to terminate the study, the investigator will complete the eCRFs as far as 
possible. The completed eCRFs and any study materials will then be collected by Valtech. 
 
13.3  Sponsor study files 
Valtech will maintain copies of correspondence, data, shipment of devices, adverse device effects 
and other records related to the investigational plan. Valtech will maintain records related to the 
signed Investigator’s Agreements. 
 

 
 
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14 REFERENCES 
1. Neuhold S et al. 2013. Impact of tricuspid regurgitation on survival in patients with chronic 
heart failure: unexpected findings of a long-term observational study. J., Eur Heart J, Vol. 34, 
pp. 844-52. 
2. Agricola E et al. 2012. Impact of functional tricuspid regurgitation on heart failure and death 
in patients with functional mitral regurgitation and left ventricular dysfunction.  Eur J Heart 
Fail, Vol. 14, pp. 902-8. 
3. Topilsky Y et al. 2014. Clinical outcome of isolated tricuspid regurgitation JACC Cardiovasc 
Imaging, Vol. 7, pp. 1185–1194. 
4. Stuge O and Liddicoat J. 2006. Emerging opportunities for cardiac surgeons within structural 
heart. J Thorac Cardiovasc Surg, Vol. 132, pp. 1258–61. 
5. Nath J et al. 2004. Impact of tricuspid regurgitation on long-term survival. J Am Coll Cardiol, 
Vol. 43, pp. 405–9. 
6. Agarwal S. et al. 2009. Interventional cardiology perspective of functional tricuspid 
regurgitation. Circ Cardiovasc Interv, Vol. 2, pp. 565-73. 
7. Supino PG et al. 2006. The epidemiology of valvular heart disease: a growing public health 
problem.  Heart Fail Clin, Vol. 2, pp. 379-93. 
8. Nishimura RA 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. Jul;148(1):2014 
9. Vahanian A. 2012. 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 Oct;42(4):S1-4 
10.  Arsalan M. et al. 2015. Tricuspid regurgitation diagnosis and treatment .2015, Eur Heart J.  
Eur Heart J. 2015 Sep 10. 
11. Navia JL et al. 2010. Surgical management of secondary tricuspid valve regurgitation: 
annulus, commissure, or leaflet procedure?  J Thorac Cardiovasc Surg. Vol. 139, pp. 1473-
1482.  
12. Cheng R et al. 2015.Tricuspid Regurgitation, the Forgotten Valvular Lesion.  Rev Cardiovasc 
Med, Vol. 16, pp. 171-81. 
13. Mutlak D. et al. 2009. Functional tricuspid regurgitation in patients with.    J. 2009, Chest, Vol. 
135. 
14. Mutlak D. et al. 2007. Echocardiographybased spectrum of severe tricuspid regurgitation: the 
frequency of apparently idiopathic tricuspid regurgitation.    J Am Soc Echocardiogr, Vol. 20, 
pp. 405-8. 

 
 
TRI-REPAIR –    TrIcuspid Regurgitation  RePAIr 
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15. Taramasso M. et al. 2012. The Growing Clinical Importance of Secondary Tricuspid 
Regurgitation. Journal of the American College of Cardiology, Vol. 59, pp. 703-710. 
16. King RM et al. 1984. Surgery for tricuspid regurgitation late after mitral valve replacement.    
Circulation, Vol. 70, pp. 193-7. 
17. O'Neill WW and O'Neill BP. 2015. Transcatheter tricuspid valve intervention: the next frontier.    
J Am Coll Cardiol, Vol. 31, pp. 1196-8. 
18. Huang X. et al.2014. Repair of functional tricuspid regurgitation: comparison between suture 
annuloplasty and rings annuloplasty. Ann Thorac Surg., Vol. 97, pp. 1286-92. 
19. Guenther T. et al. 2013. Tricuspid valve repair: is ring annuloplasty superior? Eur J 
Cardiothorac Surg, Vol. 43, pp. 58-65. 
20. Ghoreishi M. et al.2011. Undersized tricuspid annuloplasty rings optimally treat functional 
tricuspid regurgitation.  Ann Thorac Surg., Vol. 92, pp. 89-95. 
21. Ratschiller T. et al. 2014. Early experiences with a new three-dimensional annuloplasty ring 
for the treatment of functional tricuspid regurgitation. Ann Thorac Surg, Vol. 98, pp. 2039-44. 
22. Yoda M. et al. 2011. Mid-term results of tricuspid annuloplasty using the MC3 ring for 
secondary tricuspid valve regurgitation. Interact Cardiovasc Thorac Surg., Vol. 13, pp. 7-10. 
23. Jung SH. et al. 2010. Outcomes following use of a modified Duran ring tricuspid valve 
reconstruction procedure for secondary tricuspid regurgitation Circ J., Vol. 74, pp. 925-30. 
24. Onoda K. et al. 2000. Long-term follow-up after Carpentier-Edwards ring annuloplasty for 
tricuspid regurgitation. Ann Thorac Surg, Vol. 70, pp. 796-9. 
25. Gatti G. et al. 2007. Tricuspid valve annuloplasty with a flexible prosthetic band. Interact 
Cardiovasc Thorac Surg., Vol. 6, pp. 731-5. 
26. Anyanwu AC and Adams DH.2010. Functional tricuspid regurgitation in mitral valve disease: 
epidemiology and prognostic implications. Semin Thorac Cardiovasc Surg., Vol. 22, pp. 69-
75. 
27. Rogers JH and Bolling SF. 2010. Valve repair for functional tricuspid valve regurgitation: 
anatomical and surgical considerations. Semin Thorac Cardiovasc Surg., Vol. 22, pp. 84-9. 
28. Matsuyama K. et al.2003. Predictors of residual tricuspid regurgitation after mitral valve 
surgery.   Ann Thorac Surg. Vol. 75, pp. 1826-8. 
29. Sagie A. et al. 1997. Echocardiographic assessment of mitral stenosis and its associated 
valvular lesions in 205 patients and lack of association with mitral valve prolapse. J Am Soc 
Echocardiogr, Vol. 10, pp. 141-8. 
30. Boyaci, V. et al. 2007. Outcome of significant functional tricuspid regurgitation late after mitral 
valve replacement for predominant rheumatic mitral stenosis. Angiology, Vol. 58, pp. 336-42. 

 
 
TRI-REPAIR –    TrIcuspid Regurgitation  RePAIr 
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31. Izumi, K. et al. 2002. Progression of isolated tricuspid regurgitation late after mitral valve 
surgery for rheumatic mitral valve disease. J Heart Valve Dis, Vol. 11, pp. 353–356. 
32. Porter, Y. et al. 1999. Tricuspid regurgitation late after mitral valve replacement: clinical and 
echocardiographic evaluation.  J Heart Valve Dis, Vol. 8, pp. 57–62. 
33. Matsunaga A and Duran CM. 2005, Progression of tricuspid regurgitation after repaired 
functional ischemic mitral regurgitation. Circulation, Vol. 112, pp. 453-7. 
34. De Bonis M. et al. 2008. Evolution of tricuspid regurgitation after mitral valve repair for 
functional mitral regurgitation in dilated cardiomyopathy. Eur J Cardiothorac Surg, Vol. 33, 
pp. 600-6. 
35. Dreyfus GD. Et al. 2005. Secondary tricuspid regurgitation or dilatation: which should be the 
criteria for surgical repair? Ann Thorac Surg., Vol. 79, pp. 127–132. 
36. Ruel M. et al. 2004. Late incidence and predictors of persistent or recurrent heart failure in 
patients with mitral prosthetic valves.  J Thorac Cardiovasc Surg. Vol 128, pp. 278-83. 
37. Shiran A and Sagie A.2009. Tricuspid regurgitation in mitral valve disease incidence, 
prognostic implications, mechanism, and management. J Am Coll Cardiol, Vol. 53, pp. 401-
8. 
38. Mangoni AA. Et al. 2001. Outcome following isolated tricuspid valve replacement. Eur J 
Cardiothorac Surg., Vol. 19, pp. 68–73. 
39. Hornick P. et al. 1996. Tricuspid valve replacement subsequent to previous open heart 
surgery.  J Heart Valve Dis, Vol. 5, pp. 20-5. 
40. Kwon DA. Et al. 2006. Prediction of outcome in patients undergoing surgery for severe 
tricuspid regurgitation following mitral valve surgery and role of tricuspid annular systolic 
velocity. Am J Cardiol, Vol. 98, pp. 659-61. 
41. Sanfelippo PM. Et al. 1976. Tricuspid valve prosthetic replacement. Early and late results 
with the Starr-Edwards prosthesis.  J Thorac Cardiovasc Surg., Vol. 71, pp. 441-5. 
42. Bateman MG. et al. 2013. The clinical anatomy and pathology of the human atrioventricular 
valves: implications for repair or replacement. J Cardiovasc Transl Res, Vol. 6, pp. 155-65. 
43. Montant P. et al. 2009. Long-term survival in asymptomatic patients with severe degenerative 
mitral regurgitation: a propensity score-based comparison between an early surgical strategy 
and a conservative treatment approach.  J Thorac Cardiovasc Surg, Vol. 133, pp. 1339-48. 
44. Smith CR et al. 2011.Transcatheter versus surgical aortic-valve replacement in high-risk 
patients. N Engl J Med, Vol. 364, pp. 2187-98. 
45. Leon MB et al. 2010. Transcatheter aortic-valve implantation for aortic stenosis in patients 
who cannot undergo surgery.  N Engl J Med, Vol. 363, pp. 1597–607. 

 
 
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46. Maisano F. et al. 2015. Cardioband, a transcatheter surgical-like direct mitral valve 
annuloplasty system: early results of the feasibility trial. Taramasso M, Nickenig G. 2015, Eur 
Heart J.   
47. Maisano F. et al. 2014. First-in-man transseptal implantation of a "surgical-like" mitral valve 
annuloplasty device for functional mitral regurgitation.  JACC Cardiovasc Interv. Vol 7, pp. 
1326-8. 
48. Cheung A. et al. 2014. Short-term results of transapical transcatheter mitral valve 
implantation for mitral regurgitation.  J Am Coll Cardiol, Vol. 64, pp. 1814-9. 
49. Kefer J. et al. 2014. Transcatheter Sapien valve implantation in a native tricuspid valve after 
failed surgical repair.  Catheter Cardiovasc Interv, Vol. 83, pp. 841-5. 
50. Lauten A. et al. 2011. Heterotopic transcatheter tricuspid valve implantation: first-in-man 
application of a novel approach to tricuspid regurgitation.  Eur Heart J, Vol. 32, pp. 1207-13. 
51. Schofer J. 2015. First-in-human transcatheter tricuspid valve repair in a patient with severely 
regurgitant tricuspid valve.  J Am Coll Cardiol, Vol. 65, pp. 1190-5. 
52. PMA 100009: Abbott Vascular MitraClip Clip Delivery System. FDA Executive Summary for 
the March 20, 2013 Meeting of the Circulatory System Devices Panel 
53. Braun J. et al. 2008. Restrictive mitral annuloplasty cures ischemic mitral regurgitation and 
heart failure. Ann Thorac Surg  85(2):430-6;   
54. Gummert JF et al. 2003.  . Mitral valve repair in patients with end stage cardiomyopathy: who 
benefits? Eur J Cardiothorac Surg 2003; 23(6): 1017-22; Discussion 1022 
55. 1340CLD Rev 2_Cardioband Tricuspid Literature Search Report 
 
 
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