VIVO Non-invasive Time Assessment Protocol
Phase: NA
Conditions: Ventricular Tachycardia, Ventricular Ectopic Beat(S)
Sponsor: Royal Brompton & Harefield NHS Foundation Trust

 
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VIVOTM non-invasive Time Assessment Protocol 
 
 
 
 
Short Study Title/Acronym: VIVOTM mapping Protocol  
 
REC Reference: Insert REC Reference 
IRAS Reference: 257755 
 
 
CHIEF INVESTIGATOR: 
 
Dr Sabine Ernst, Consultant Cardiologist and Reader in Cardiology, Lead for 
Electrophysiology Research for the Royal Brompton Hospital 
Royal Brompton Hospital (RBH) 
Sydney Street 
London SW3 6NP 
 
Phone: 00442073518612 
Email: s.ernst@rbht.nhs.uk 
Fax: 00442073518131 
 
SPONSOR REPRESENTATIVE: 
 
Mr Patrik Pettersson 
Royal Brompton and Harefield NHS Foundation Trust (RB&HFT) 
Royal Brompton Hospital (RBH) 
Research Office  
Chelsea Wing, Level 2 
Sydney Street 
London SW3 6NP 
 
Phone: 0207 352 8121 ext. 8736  
Email: P.Pettersson@rbht.nhs.uk  
Fax: 0207 351 8829 
 
 
 

 
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Information in this protocol is confidential and should not be disclosed, other than to those directly involved in the 
execution or the ethical review of the study, without written authorisation from RB&HFT Research Office. 
 
 
 
 
Signature Page  
The Chief Investigator (CI) and the Research Office have discussed and agreed this study 
protocol. The investigators agree to perform the investigations outlined in this study protocol 
and to abide by this protocol except in the case of medical emergency that will be notified to 
the Research Office. 
 
The Investigator agrees to conduct the study in compliance with the study protocol and/or 
any subsequent amendments approved by the Sponsor and HRA, the Data Protection Act 
(1998), the Trust Information Governance Policy (or other local equivalent as applicable), 
the Research Governance Framework for Health & Social Care, 2nd Edition (2005), the 
Sponsor’s SOPs, and any other applicable regulatory requirements. 
 
This protocol has been written in accordance with the Sponsor’s guidance for writing non-
CTIMP protocols.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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Table of contents 
 
1. 
LIST OF ABBREVIATIONS 
5 
2. 
STUDY PERSONNEL AND FACILITIES 
6 
3. 
STUDY SYNOPSIS 
8 
4. 
INTRODUCTION 
9 
4.1 
BACKGROUND 
9 
4.2 
PRE-CLINICAL DATA/CLINICAL DATA 
9 
4.3 
STUDY RATIONALE AND RISK/BENEFIT ANALYSIS 
10 
4.4 
MANAGEMENT OF POTENTIAL STUDY RISKS 
12 
5. 
STUDY OBJECTIVES 
12 
5.1 
PRIMARY OBJECTIVE 
13 
5.2 
SECONDARY OBJECTIVES 
13 
6.1 
OVERALL DESIGN 
14 
6.2 
TREATMENT AND RATIONALE 
14 
6.3 
SCHEMATIC OF STUDY DESIGN 
14 
7. 
ELIGIBILITY CRITERIA 
15 
7.1 
INCLUSION CRITERIA 
17 
7.2 
EXCLUSION CRITERIA 
17 
7.3 
DISCONTINUATION/WITHDRAWAL OF PARTICIPANTS AND STOPPING RULES 
17 
8. 
SUBJECT/PATIENT RECRUITMENT PROCESS 
17 
9. 
STUDY PROCEDURES 
18 
9.1 
INFORMED CONSENT 
18 
9.2 
RANDOMISATION PROCEDURE 
19 
9.3 
EMERGENCY UN-BLINDING 
19 
10. 
STUDY ASSESSMENTS 
19 
10.1 
SCREENING ASSESSMENTS 
19 
10.2 
BASELINE ASSESSMENTS 
20 
10.3 
TREATMENT PROCEDURE 
20 
10.4 
SUBSEQUENT ASSESSMENTS 
21 
10.5 
SUMMARY CHART OF STUDY ASSESSMENTS 
22 
11. 
METHODS 
22 
11.1 
Laboratory Procedures 
23 
11.2 
Radiology or any other procedure(s) – Please define applicable procedure(s) in this heading
 
23 
11.3 
DEFINITION OF THE END OF STUDY 
24 
12. 
SAFETY REPORTING 
24 
12.1 
DEFINITIONS 
24 
12.2 
RECORDING ADVERSE EVENTS (AES) 
24 

 
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12.2 
ASSESSMENT OF SAES 
24 
12.3 
REPORTING OF SAES TO THE SPONSOR AND THE REC 
25 
12.4 
THE TYPE AND DURATION OF THE FOLLOW-UP OF SUBJECTS AFTER AES 
26 
12.5 
PREGNANCY 
26 
12.6 
ANNUAL PROGRESS REPORTS (APRS) 
26 
12.7 
REPORTING URGENT SAFETY MEASURES 
26 
13. 
DATA MANAGEMENT AND QUALITY ASSURANCE 
27 
13.1 
 CONFIDENTIALITY 
27 
13.2 
 DATA COLLECTION TOOL 
27 
13.3 
DATA HANDLING AND ANALYSIS 
28 
13.4 
ARCHIVING ARRANGEMENTS 
28 
14. 
STATISTICAL DESIGN 
28 
14.1 
SAMPLE SIZE AND RECRUITMENT 
29 
14.2 
ENDPOINTS 
29 
14.2.1 
 Primary endpoints 
29 
14.2.2 Secondary endpoints 
30 
14.3 
STATISTICAL ANALYSIS PLAN 
30 
14.3.1 
Primary endpoint analysis 
Error! Bookmark not defined. 
14.3.2 
Secondary endpoint analysis 
Error! Bookmark not defined. 
14.4 
RANDOMISATION 
31 
14.5 
INTERIM ANALYSIS (IF APPLICABLE) 
31 
14.6 
OTHER STATISTICAL CONSIDERATIONS 
31 
15. 
COMMITTEES INVOLVED IN THE STUDY 
31 
16. 
MONITORING AND AUDITING 
31 
17. 
DIRECT ACCESS TO SOURCE DATA 
31 
18. 
ETHICS AND REGULATORY REQUIREMENTS 
31 
19. 
FINANCE 
32 
20. 
INSURANCE AND INDEMNITY 
32 
21. 
PUBLICATION POLICY 
32 
22. 
STATEMENT OF COMPLIANCE 
33 
23. 
LIST OF PROTOCOL APPENDICES 
33 
24. 
REFERENCES 
34 
 
 
 
 
 
 
 
 
 
 

 
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1. LIST OF ABBREVIATIONS  
 
        VT         
                 ventricular tachycardia 
        PVC    
 
                 premature ventricular contraction 
        HR      
 
 
       heart rate 
        LV 
 
 
       left ventricle 
        RV 
  
 
       right ventricle 
        RVOT  
 
 
       right ventricular outflow tract 
        RF 
 
 
       radiofrequency current 
        EAM 
  
 
       electroanatomical mapping 
        EGM      
 
       electrogram 
        TOE  
  
 
       transesophageal echocardiography 
        TTE       
                  transthoracic echocardiography 
        ECG      
 
       electrocardiogram 
        CT  
  
 
       computer tomography 
        F/U 
  
 
       follow-up 
        EP  
  
 
       electrophysiology 
       QoL       
                 quality of life 
        PI          
                 principal investigator 
        CMR 
  
 
       cardiac magnetic resonance imaging 
        VTK      
 
       visualization toolkit 
RB&HFT   
 
       Royal Brompton and Harefield NHS Foundation Trust 
AE 
Adverse Event 
AR 
Adverse Reaction 
ASR 
Annual Safety Report 
CI 
Chief Investigator 
CRF 
Case Report Form 
DMC 
Data Monitoring Committee 
GCP 
Good Clinical Practice 
HRA 
Health Research Authority  
ICF 
Informed Consent Form 
NHS R&D 
National Health Service Research & Development   
PI 
Principal Investigator 
PIS 
Participant Information Sheet 
REC 
Research Ethics Committee 
SAR 
Serious Adverse Reaction 
SAE 
Serious Adverse Event 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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2. STUDY PERSONNEL AND FACILITIES 
 
Principal Investigator (PI):  Dr Sabine Ernst 
Consultant Cardiologist and Reader in Cardiology Lead 
for Electrophysiology Research for the Royal Brompton 
Hospital 
 
 
 
 
 
Royal Brompton Hospital (RBH) 
 
 
 
 
 
Sydney Street 
 
 
 
 
 
London SW3 6NP 
 
 
 
 
 
 
 
 E-mail:  s.ernst@rbht.nhs.uk 
Phone:  00442073518612 
 
 
 Fax: 00442073518131 
 
Co-Investigators:    
 
Dr Ilaria Cazzoli 
 
 
 
 
 
Clinical and Research Fellow 
 
 
 
 
 
Royal Brompton Hospital (RBH) 
 
 
 
 
 
Sydney Street 
 
 
 
 
 
London SW3 6NP 
 
 
 
 
 
 
E-mail: I.Cazzoli@rbht.nhs.uk 
 
 
Additional electrophysiology consultants at the Royal Brompton Hospital and Specialist 
registrars in Electrophysiology. 
 
 
Statistician:                         Mr Winston Banya 
Royal Brompton and Harefield NHS Foundation Trust 
(RB&HFT) 
Royal Brompton Hospital (RBH) 
Research Office  

 
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Chelsea Wing, Level 2 
 
 
 
 
 
Sydney Street 
 
 
 
 
 
London SW3 6NP 
 
 
 
 E-mail:  W.Banya@rbht.nhs.uk 
Phone:  00442073512707 
 
 
 
 
 
Routine local laboratories: Royal Brompton Hospital 
 
 
 
 
Central Laboratory: 
Royal Brompton Hospital 
 
Pharmacy: 
Royal Brompton Hospital 
 

 
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3. STUDY SYNOPSIS 
 
 
Full study title: 
VIVOTM non-invasive Time Assessment Protocol 
Short study title:  
VIVOTM mapping Protocol 
Study R&D number: 
VIVO-RBH01 
Chief Investigator: 
Dr Sabine Ernst 
Medical 
condition/disease 
under investigation: 
Patients undergoing PVC/VT Ablation with structurally normal hearts 
Study duration: 
9 months 
Primary Objective: 
Safety: 
• 
Absence of acute adverse events due to the use of VIVO system 
during PVC/VT ablation 
• 
Safety endpoint of the entire mapping and ablation strategy 
Efficacy: 
• 
To assess the efficacy of VIVO to decrease procedure time as 
compared to standard of care ablation procedures. 
Secondary  
Objective:  
• 
To assess clinical outcome (suppression of reduction of PVCs 
burden/VT at 3-month F/U) 
• 
To assess economical outcome (cost reduction per case) 
Study population:  
VIVO Cohort – 15 patients presenting for PVC/VT ablation with 
structurally normal heart  
Control Cohort – Retrospective review of historical matched patients 
within the physician’s database that had PVC/VT ablations with 
structurally normal hearts 
Recruitment Target 
15 patients 
Recruitment Window 
(Months) 
6 months 
Methodology:  
The study is a non-randomized, single-centre, study designed to evaluate 
the procedural efficacy of VIVO as compared to standard of care ablation 
procedures.  Up to 15 patients will be enrolled. 
Eligibility criteria: 
Inclusion criteria: 
1. Subjects who are at least 18 years or older 
2. Subjects who are scheduled for PVC/VT ablation procedure  
3. Subjects who have signed an IRB/EC approved Informed Consent 
Form and applicable subject privacy protection authorization per 
local law  
4. Subjects will be selected without regard to gender or age (unless 
precluded by local regulatory requirements)   
5. Subjects with or without cardiac structural disease 
 
Exclusion criteria: 
1. Reversible causes of PVC/VT 
2. Subjects with recent (within 3 months) acute coronary syndrome 
3. Subjects who are contraindicated for CT or MRI (must be able to 
get one) 

 
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4. Subject whose MRI or CT scan does not comply with the 
requirements of this protocol 
5. Subjects who are contraindicated for an electrophysiology 
procedure and/or fluoroscopy: 
6. INR > 3.5 
7. Active infection 
8. Pregnancy: Females of childbearing potential with a positive 
pregnancy test. 
9. Existing mechanical heart valve 
10. Subjects with structural cardiac disease 
 
 
Study treatment: (i.e. dose and mode of the study drug administration if applicable): NA 
4. INTRODUCTION 
4.1 BACKGROUND 
Accurate localization of the origin of focal ventricular arrhythmias is a prerequisite to 
successful catheter ablation1. Nevertheless, mapping and determining the arrhythmic foci is 
time consuming, invasive and difficult. Catheter ablation guided by VT activation mapping 
has evolved to treat scar-related arrhythmias with up to 75% success rate after successful 
mapping procedures. However, non-sustained, non-inducible, or hemodynamically unstable 
VTs cannot be mapped with this technique. Alternatively, EP substrate mapping during sinus 
rhythm (SR) identifies the scar EP substrate based on low voltage and the presence of 
fractionated EGMs and late potentials (LPs). Conventionally, pre-procedural diagnosis and 
localization of cardiac arrhythmias has been done by the 12 lead ECG 2. However, 12-lead 
ECG arrhythmia-origin algorithms have limitations and may negatively influence ablation 
outcomes. For example, erroneous identification may result in unnecessary mapping and 
failure to identify the treatable target 3.  
 
VIVO was developed to easily determine the location of PVC/VT foci and to reduce 
mapping/identification time. VIVO improves upon the non-invasive 12 lead ECG by 
combining the ECG data with an already acquired CT/MR image and a 12 lead ECG to create 
a patient specific model, thus improving the localization accuracy 4-10. 
 
4.2 PRE-CLINICAL DATA/CLINICAL DATA 
4.2.1 Early Development Study 
First in man studies were conducted at the University of California, Los Angeles using the 
initial VIVO software and algorithm. During the study, the software capabilities and 
algorithm were fine tuned to improve the accuracy of PVC and VT foci. 
The study enrolled 20 patients and had no complications or safety concerns. VIVO correctly 
identified 100% of the PVC, VT, or stimulation sites to the correct region. Publications from 
this study are in Attachment A. 

 
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4.2.2 Clinical Validation 
Previously, 22 patients were enrolled and analysed in a study at Johns Hopkins University 
Hospital (Baltimore, Maryland) without complications related to VIVO (Satish Misra et al, 
2018). Prior to the procedure, imaging (contrast enhanced CT or MRI) was acquired based 
on the institution’s protocol. In addition, a 3D image (to determine ECG lead placement) and 
ECG data (extracted from CardioLab) were also acquired pre-procedure. Image 
segmentation, surface electrode registration, and PVC/VT analysis was performed post-
procedurally using the VIVO analysis software. VIVO identification of PVCs and VTs was then 
compared to invasive electro-anatomical mapping (EAM). A PVC location was defined as a 
site of earliest activation during electroanatomic mapping and/or site of successful ablation. 
VT was defined as (a) operator defined exit site (b) area of successful ablation. 
 
Results of the study are below: 
• 
22 patients 
• 
19/22 locations determined by VIVO were a match to standard mapping systems 
• 
No safety concerns 
• 
Zero complications 
 
A further trial for FDA approval is currently underway with US and European centres 
contributing. 
 
4.3 STUDY RATIONALE AND RISK/BENEFIT ANALYSIS 
4.3.1 Mapping PVC/VT 
Outflow tract ventricular tachycardia or frequent premature ventricular tachycardia (PVCs) 
often occur in the absence of structural heart disease and account for 10% of all ventricular 
tachycardia (VT). The majority of these originate from the right ventricular outflow tract and 
the remainder from the left ventricular outflow tract, including cusps of the aortic valve 10. 
Eighty to 90% of tachycardia in normal hearts originate from the right ventricle, most 
commonly the right ventricular outflow tract (RVOT)11. 
Especially in ischaemic patients, but not only, scar-related re-entry ventricular arrhythmia 
may involve the endocardium, mid-myocardium, and epicardium. Importantly, the presence 
of epicardial VT circuits (in about 32% of patients with post-myocardial infarction scars) is 
considered one of the reasons for failure of a subset of endocardial ablations. Consequently, 
epicardial mapping via subxyphoidal puncture has evolved as an essential procedure for 
mapping epicardial scar EP substrate and guiding epicardial ablation, especially in ischaemic 
cardiomyopathy patients with failed endocardial ablation. Epicardial mapping is associated 
with procedural complexity and risk of complications. In some cases, catheter access to the 
epicardium is limited by the presence of pericardial adherence. Non-invasive mapping of 
epicardial EP substrate and VT activation is therefore a highly desirable procedure. It could 
aid in deciding whether endocardial or epicardial approach should be used and provide 
important information for the pre-procedural planning of epicardial ablation. With regards to 

 
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endocardial foci, a precise anatomical localization of the “clinical” PVC/VT morphology is 
critical for the success of the ablation procedure, especially in the setting of 
hemodynamically poorly tolerated arrhythmias. Over the recent years, the only non-invasive 
electrocardiographic imaging mapping system validated in the EP laboratory was the 
CardioInsight (Medtronic, MN, USA), whose accuracy in distinguishing endocardial from 
epicardial or papillary muscles arrhythmia origin is however limited (margin of error ~6mm).  
Unlike other existent systems, VivoTM non-invasive mapping system offers an easier and 
more accurate localization of PVC/VT foci, allowing to distinguishing endo- from epicardial 
foci with a high accuracy even with regards to more complex or smaller structures (i.e. 
anterior from posterior aspect of a papillary muscle, or aortic cusps). The use of such 
system in a pre-procedural phase can therefore not only increase the success rate of the 
ablation itself, but also potentially decrease the procedural time (resulting ideally in a 
reduction of the procedural costs) and radiation exposure time, without adding any risk to 
the overall procedure. 
 
4.3.2 Procedure Requirements 
 
4.3.2a  Prior to EP Procedure 
 
Prior to the procedure the subject will undergo cardiac and thoracic imaging. This can be in 
the form of a MRI or CT scan, based on physician preference. Specific MRI and CT scan 
protocols do not significantly differ from the protocols already in use at the Brompton for 
pre-procedure roadmap scan. The recorded DICOM images should be provided the physician 
to upload into VIVO for future segmentation. The Mortara 12-lead Holter will be used to 
record the patient’s PVCs templates (with their respective frequency of presentation). The 
recorded files will be then imported into Vivo analysis software for the analysis and 
localization on the pre-reconstructed model. Likewise, the analysis will be done with 
templates from the Sensis software in the catheter laboratory.  
 
The 3 D Camera will be used to take a 3D image of the patient’s torso after ECG lead 
placement. This will be merged with the cardiac anatomy from the 3D scan.  
 
 
4.3.2b During the EP procedure 
 
The EP procedure will be completed per the Institution’s standard of care using a 3D 
electroanatomical mapping system (CARTO, Biosense Webster).  
The information from VIVO analysis will be integrated in the 3D mapping process such that 
the ablation procedure will be provided with this information, or in post-processing to 
establish the accuracy of the localization.   
Pacing locations can be selected at any time during the procedure based on the physician’s 
preference.  
 

 
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4.3.2c  Registration of EAM to Imaging  
 
Left sided ablations: A Carto mapping catheter will be used to generate a complete fast 
anatomic map (FAM) anatomic shell of the left ventricle for identification of cardiac 
structures related to imaging. Imaging should be acquired at End Diastole. Landmarks will 
include those that are required for the individual procedure, including the papillary muscles 
if pacing is planned on the papillary muscles.  
 
Right sided ablations: A Carto mapping catheter will be used to generate a complete fast 
anatomic map of the entire right ventricle and right ventricular outflow tract. Landmarks will 
include those that are required for the individual procedure.  
 
4.3.2d  Identifying the location of PVC or VT Origin 
 
Identification with VIVO: Identifying the location of the PVC or VT foci with VIVO will be 
done prior to the patient’s procedure.  
 
Identification with CARTO: Identifying the location of the PVC or VT foci with Carto can be 
done at any time during the procedure based on physician preference. Once determined this 
point should be acquired in CARTO and tagged as Site of Origin. If the Site of Origin cannot 
be determined by Carto, the “best guess” location will be identified at the discretion of the 
physician. 
 
 
4.3.2e  Pro-procedure / Post-procedure processing  
 
We will generate a screenshot of each pacing site and the clinical PVC/VT in an orientation 
that allows adequate visualization of the pacing and arrhythmia locations.  
The physician in charge of the analysis will generate a screen shot of the final VIVO analysis 
for comparison to the Carto screenshots. This will be reviewed with the physician to 
determine if the VIVO analysis location matches the location identified by Carto.  
An electronic copy of the screenshots will be placed in the patient’s study file. 
 
 
4.4 MANAGEMENT OF POTENTIAL STUDY RISKS 
Risks 
There is no additional risk onto the already well-established risks of catheter ablation of 
PVC/VT/VF. 
 
CT scan (only if patient has a contra-indication for CMR scans) 

 
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The scan is acquired in a single breath hold during expiration from the level of the acromial 
processes to the dome of the diaphragm and starts with the 80 mls injection of contrast 
agent with Omnipaque 350 mg/ml followed by 20 mls of saline at a flow rate of 5 mls per 
second. 
  
Cardiac CT performed on retrospective ECG gated CT imaging (end diastole) using tube 
modulation technique and adjusting the kvp according to BMI (100 kvp if BMI<30 and 120 
kvp if BMI >30 kg/m2). There could be adverse reactions to the intravenous contrast agent. 
Patients with renal impairment would be excluded from this study.  
Clinical protocols are in place to manage anaphylaxis which is however very rare.  
 
Mapping with VIVO system and catheter ablation 
We anticipate that mapping with VivoTM system will not prolong the overall procedure 
duration or any technical aspect of the catheter ablation. As it is a non-invasive system 
intended to provide an accurate localization of the arrhythmia foci, most part of the work 
will be carried out in a pre-procedural phase (anatomy reconstruction from the pre-acquired 
scan, ECG template acquisition and arrhythmia foci localization on the virtual model). Also, 
the radiation exposure time for operator and patient is overall comparable to conventional 
procedures.  
 
We will use an amended version of the already routinely used consent form for PVC/VT 
ablation used in the Trust to outline the inherent risk of an ablation for PVCs/VT/VF.  
 
 
5. STUDY OBJECTIVES 
5.1 PRIMARY OBJECTIVE 
Our hypothesis is that patients with PVCs/VT who must undergo catheter ablation can 
benefit from a VIVO non-contact mapping and guided ablation in terms of efficacy to 
decrease the procedural time of the ablation and acute success.   
 
 
5.2 SECONDARY OBJECTIVES 

 
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We will assess the efficacy of Vivo non-invasive mapping system guided ablation with 
regards to safety and clinical outcome. Furthermore, we will assess if the precise 3D a priori 
knowledge of the arrhythmia exit site shortens the procedure and how large thereby the 
reduction of costs per single case is, as compared to historic controls. 
 
 
6. STUDY DESIGN 
 
6.1 OVERALL DESIGN 
This is a prospective, single arm, observational and feasibility study, which will recruit 15 
non-selected patients, with structurally normal heart, with a conventional indication for 
catheter ablation of PVCs/VT. The follow up will be of three months. The study will also 
include another retrospective cohort, including age & gender matched patients, without 
cardiac structural disease, with a conventional indication for catheter ablation of PVCs/VT 
from the last 5 years’ database of the same operator. For this second retrospective cohort 
there will be no follow-up.   
 
6.2 TREATMENT AND RATIONALE 
A three month follow up period after ablation of PVC/VT is a long enough time frame which 
allows us to assess the effect of the ablation on suppression/reduction of arrhythmia 
burden. Patients will be followed-up at 3 months following the ablation procedure. Early 
recurrences will be treated by uptitrating/changing/addition of anti-arrhythmic medication 
and/or DCCV if persistent arrhythmia. If further arrhythmia occurs despite these measures, 
a re-ablation procedure will be offered. If further episodes occur, patients can be offered a 
second ablation procedure or continuation of medical management. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.3 SCHEMATIC OF STUDY DESIGN 

 
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Pre-ablation 
Pre-
discharge 
3 months 
12 lead ECG  
 
X (routine) 
X (routine) 
Telemetry 
X (routine) 
 
 
Contrast CT 
scan or non-
contrast CMR 
for roadmap 
X (routine) 
 
 
TTE 
 
x (routine) 
 
Symptom 
questionnaire 
X (research) 
 
X (research) 
Clinic Visit 
 
 
X (EP OPC) 
ECG Holter 
(Mortara) 
X (research) 
 
X (research) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
VIVOTM non-invasive Time Assessment 
Protocol 
 
(Vivo protocol) 

 
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Non-selected patients eligible for PVC/VT 
catheter ablation  
with structural normal heart  
 
According to ESC/AHA/ACC guidelines 
Check for inclusion/exclusion criteria 
Obtain informed consent 
 
Roadmap scan  
(CMR or CT scan) 
Prospective Arm (n=15) 
- Anatomy reconstruction and arrhythmia 
localization using Vivo software 
- Procedure carried out as per standard of care 
- Comparison between ablation sites and Vivo 
localization sites after the procedure 
- Catheter ablation carried out according to the 
localised sites +/- additional RF deliveries 
(discretion of the operator) 
 
 
Follow-up for total of 3 months  
12-lead ECG Holter (Mortara) 

 
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7. ELIGIBILITY CRITERIA 
7.1 INCLUSION CRITERIA 
• 
Subjects who are scheduled for PVC/VT ablation procedure, without structural heart 
disease 
• 
Age >18 years old and ≤ 80 years 
• 
Fulfil established clinical criteria for catheter ablation of PVC/VT  
• 
Subjects who are at least 18 years or older 
• 
Subjects who have signed an approved Informed Consent Form and applicable 
subject privacy protection authorization  
• 
Subjects will be selected without regard to gender or age  
7.2 EXCLUSION CRITERIA 
• 
Reversible cause of PVC/VT 
• 
Recent cardiovascular event including TIA 
• 
Structural heart disease 
• 
Intolerance or unwillingness to oral anticoagulation with Warfarin 
• 
Bleeding disorder 
• 
Contraindication to CT scan  
• 
Presence of intracardiac thrombus 
• 
Vascular disorder preventing access to femoral veins 
• 
Severe, life threatening non-cardiac disease 
• 
Active malignant disease and recent (<5 years) malignant disease 
• 
Unable or unwilling to comply with F/U requirements 
• 
Renal impairment  
• 
Pregnancy 
 
7.3 DISCONTINUATION/WITHDRAWAL OF PARTICIPANTS AND STOPPING RULES 
There are no major additional hazards related to the use of Vivo mapping system to guide 
the ablation, and the rest of the procedure is carried on using an established ablation 
strategy. The only difference is in the pre-procedural phase, when Vivo software will be used 
to localise the ablation targets. Therefore, we do not expect that patients will develop major 

 
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side effects related to the intervention tested in this study to warrant withdrawal. However, 
if patients present with acute medical conditions non-related to the study or new diagnosis 
are made during the follow-up period, such as active malignant disease, they can be 
withdrawn from the study. Additionally, patients can be withdrawn on their own request. 
The patients thus withdrawn from the study will continue to be followed-up regularly in the 
arrhythmia clinic. There are no major foreseeable circumstances under which the trial will 
need to be stopped prematurely, other than technical limitations. 
8. SUBJECT/PATIENT RECRUITMENT PROCESS 
Patient recruitment at a site will only commence once the study team has ensured that the 
following approval/essential documents are in place:  
 
1. HRA approval,  
2. Local Site Delegation of Duties and Signature Log is completed (if applicable). 
 
The Royal Brompton Hospital is the single site participating in the trial and will be asked to 
provide a copy of the following:  
 
1. Signed Clinical study Site Agreement (CSSA) (if applicable) 
2. Confirmation of capacity and capability 
 
All subjects who wish to enter the study will be fully screened and consented by the Chief 
Investigator (CI), Principal Investigator or Co-Investigator.  
 
We will recruit patients from those with PVC/VT who have already an indication for catheter 
ablation according to the current guidelines or have recurrent PVC/VT after previous 
catheter ablation(s). Patients will be offered participation in the study during the visit in the 
outpatient clinic. Only one centre will be involved in recruitment of the patients. All 
electrophysiology consultants in each Trust will be familiar with the protocol and be involved 
in selection of the patients.  
9. STUDY PROCEDURES  
9.1 INFORMED CONSENT 
Informed consent will be obtained by the Chief Investigator (CI), Principal Investigator (PI) 
and/or a nominated deputy as recorded on Sponsor’s Delegation of Responsibilities Log. 
Only those members of the study team who have clinical responsibility for the care of 

 
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patients under the care of the general medical service will be permitted to undertake 
informed consent.  
Due to the complexity and novelty of the Vivo study, a senior nurse or an SHO cannot take 
consent for this study. All individuals taking informed consent will have received consent 
training. Patients will be provided with the information necessary to consider their 
participation at least 24 hours before the procedure.  
 
Periods shorter than 24 hours will be permitted if the patient feels that further deliberation 
will not lead to a change in their decision, and provided the person seeking consent is 
satisfied that the patient has fully retained, understood and deliberated on the information 
given. Likewise, periods longer than 24 hours will be permitted should the patient request 
this. The Investigator or designee will explain that the patients are under no obligation to 
enter the trial and that they can withdraw at any time during the trial, without having to 
give a reason. 
 
A copy of the signed Informed Consent Form (ICF) along with a copy of the most recent 
approved Patient Information Sheet (PIS) will be given to the study participant.  The original 
signed consent form will be retained at the study site (one filed in the medical notes and 
one field in the Trial Master File (TMF)). A copy of the consent form will also be given to the 
patient. 
 
If new safety information results in significant changes to the risk–benefit assessment, the 
consent form will be reviewed and updated if necessary. All subjects, including those already 
being treated, will be informed of the new information, given a copy of the revised consent 
form and asked to re-consent if they choose to continue in the study. 
 
9.2 RANDOMISATION PROCEDURE 
This section does not apply. 
 
9.3 EMERGENCY UN-BLINDING 
This section does not apply. 
 
 
10. 
STUDY ASSESSMENTS 
10.1 SCREENING ASSESSMENTS 
 
Screening 

 
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Fifteen patients with PVC/VT and an indication for catheter ablation will be prospectively 
recruited. The screening visit will involve the following: 
 
• 
Inclusion and exclusion criteria assessment 
• 
Detailed past medical history including first diagnosis of PVC/VT and related 
symptoms 
• 
Details of any previous catheter ablation for PVC/VT 
• 
Physical examination 
• 
ECG 
• 
Evaluation of PVC/VT related symptoms  
• 
Standard echocardiography (new or up to 12 months before the procedure) 
o LVEF, LV/RV volumes, LVOT obstruction 
 
10.2 BASELINE ASSESSMENTS 
• 
Detailed past medical history including first diagnosis of PVC/VT and related 
symptoms 
• 
Physical examination 
• 
ECG 
• 
Evaluation of PVC/VT related symptoms  
• 
Standard laboratory tests  
➢ complete blood count 
➢ coagulation studies 
➢ serum creatinine and electrolytes 
➢ liver function tests 
➢ CRP 
 
10.3 TREATMENT PROCEDURE 
Using the roadmap 3D image information of the CMR or CT scan a standard three-
dimensional (3D) reconstruction will be performed (CARTO software package). The CMR or 
CT scan will be also imported into the Vivo anatomy software to reconstruct the patient’s 
model, necessary for the following localization analysis.  
 
Before the start of the ablation procedure, when still in the ward, the patient will undergo a 
12-lead ECG recording (Mortara) while contemporarily on telemetry in order to record the 
templates of the different PVC/VT morphologies, with also regards to their frequency. 
Should the patient present no ventricular arrhythmia, a challenge with exercise bike or 

 
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intravenous administration of isoprenaline or atropine could be chosen. Finally, a picture of 
the patient’s chest will be taken and imported in the software to match the ECG electrodes’ 
position.  
 
Mapping Vivo non-contact system and ablation procedure 
Once the different templates are acquired, they will be imported into the VIVO analysis 
system, and a final model with foci localization will be generated. The information will be 
integrated into the 3D mapping system prior to starting the procedure.  
After venous vascular access has been gained using an ultrasound-guided approach, an 
octapolar catheter (InquiryTM, Saint Jude Medical) will be positioned in His-RV position, 
while a mapping/ablative catheter will be used both for mapping and RF delivery. In case of 
arrhythmias originating from the LV, it is the operator’s choice to use either an arterial 
femoral access for a retrograde approach or a transseptal access route. In case of left-sided 
access, as per institutional standard, ACT measurements will be carried out every 30 min 
with bolus injections of Heparin to achieve an ACT of ≥350 sec.  
The whole ablative procedure will be carried out according to international guidelines and as 
for operator expertise and discretion. Achievement of PVC/VT suppression will be 
documented for all patients for 30 minutes after last RF delivery, with or without IV drug 
provocation challenge. DCCV may be carried out at the discretion of the operator during the 
procedure if needed.  
Removal of sheaths will be performed as per institutional standard (+/- protamine). 
 
10.4 SUBSEQUENT ASSESSMENTS 
Follow-up 
 
3 months (follow-up visit – study completion - endpoints assessment)  
The next scheduled follow-up visit after discharge will be at approximately three months 
post PVC/VT ablation. The following assessments will take place: 
 
• 
Patient’s symptoms (questionnaire) and clinical assessment  
• 
Review of medication  
• 
 12-lead ECG 
• 
12-lead Holter (Mortara) 
• 
If high PVC/ VT burden at 3 months, either therapy change or repeat ablation 
(according to patient and physician preference).  
 
 
 
 

 
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10.5 SUMMARY CHART OF STUDY ASSESSMENTS 
 
 
Pre-ablation 
Pre-
discharge 
3 months 
12 lead ECG  
 
X (routine) 
X (routine) 
Telemetry 
X (routine) 
 
 
Contrast CT 
scan or non-
contrast CMR 
for roadmap 
X (routine) 
 
 
TTE 
 
x (routine) 
 
Symptom 
questionnaire 
X (research) 
 
X (research) 
Clinic Visit 
 
 
X (EP OPC) 
ECG Holter 
(Mortara) 
X (research) 
 
X (research) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Follow up  
 
3 months 
Follow-up visit  
 
RHYTHM & SAFETY  
Review therapy, allow Re-
ablation if necessary using 
same methodology 
Assess recurrences by 12-
lead Mortara Holter 

 
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11. 
METHODS 
11.1 Laboratory Procedures 
We will not take specific blood or tissue samples. Routine bloods will be taken at admission 
for the ablation and pre-discharge. 
 
11.2 Radiology or any other procedure(s) 
 
All patients will undergo a cardiac CMR or CT exam to be used as a roadmap during the 
ablation procedure.  The CT exam will comprise of a standard-of-care contrast-enhanced 
scan to visualise the cardiac chambers. This pre-procedure imaging is necessary in order to 
define 
the 
spatial 
anatomical 
relationship 
of 
the 
cardiac 
chambers.  
In the event that the ablation procedure needs to be repeated during follow-up, the 
roadmap scans can be re-used. 
 
As part of a conventional PVC/VT ablation procedure, the patient is exposed typically to 
about 2 mSv of ionizing radiation, occasionally increasing to 10 mSv or more, per procedure. 
If radiation is necessary to be used during any of the study procedures than efforts will be 
made to lower the exposure to as low as reasonably achievable including the re-use of the 
CT or CMR scan for 3D image integration during the ablation procedure(s).  
▪ 
Techniques and Interventions 
The technique of mapping the ventricular chambers/epicardial space in order to guide the 
PVC/VT ablation is a conventional procedure which is carried out routinely in the catheter 
labs using different mapping system according to operators’ experience and confidence. The 
here proposed study will use the VivoTM (Catheter Precision, Inc., USA) in the pre-invasive 
phase in order to guide ablation.  
 
▪ 
Tools 
All tools used for the ablation procedure will include standard materials for ablation of 
PVC/VT. The VivoTM Anatomy and Analysis software and the Kinect Camera are fully CE 
marked.  
 
▪ 
Study Drugs  
This section does not apply. 

 
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11.3 DEFINITION OF THE END OF STUDY 
The end of trial will be considered the last patient last visit (hospital visit). 
12. 
SAFETY REPORTING 
12.1 DEFINITIONS 
Adverse Event (AE) — any untoward medical occurrence in a patient or clinical study 
subject who is administered a treatment and which does not necessarily have a causal 
relationship with this treatment (i.e. any unfavourable or unintended change in the structure 
(signs), function (symptoms), or chemistry (lab data) in a subject to whom a 
treatment/study procedure has been administered, including occurrences unrelated to that 
product/procedure/device). 
Serious Adverse Event (SAE) – is defined as an untoward occurrence that: 
▪ 
Results in death; or  
▪ 
Is life-threatening (places the subject, in the view of the Investigator, at 
immediate risk of death) 
▪ 
Requires hospitalization or prolongation of existing hospitalization (hospitalisation 
is defined as an inpatient admission, regardless of length of stay; even if it is a 
precautionary measure for observation; including hospitalisation for an elective 
procedure, for a pre-existing condition) 
▪ 
Results in persistent or significant disability or incapacity (substantial disruption of 
one’s ability to conduct normal life functions) 
▪ 
Consists of a congenital anomaly or birth defect (in offspring of subjects or their 
parents taking the study drug regardless of time of diagnosis) 
▪ 
Is otherwise considered medically significant by the investigator. 
 
Important medical events that may not be immediately life-threatening or result in death or 
hospitalisation but may jeopardise the subject or may require intervention to prevent one of 
the outcomes listed in the definition of serious will also be considered serious. 
 
12.2 RECORDING ADVERSE EVENTS (AES) 
 
All Adverse Events will be recorded in the hospital notes and Case Report Form (CRF).   
If the Investigator suspects that the disease has progressed faster due to the administration 
of the study treatment/procedure, then he/she will report this as an unexpected adverse 
event to the Sponsor and the REC as detailed in Section 12.3.  
 
12.2 ASSESSMENT OF SAES 

 
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Principal Investigator (PI) at all sites must report all SAEs to the Chief Investigator (CI) or a 
delegated individual in the research team. The CI and his research team at RBH are 
responsible for reporting events to the Research Office immediately and/or within 24 hours 
of becoming aware of the event using the Sponsor’s SAE Reporting Form.   
 
Classification and causality of Adverse Events (AEs) will be conducted by local PIs and 
reviewed by CI. The CI cannot downgrade the site PI’s classification and if there is 
disagreement which cannot be resolved during formal discussion then the assessment of the 
site PI will be accepted. The CI, can however, upgrade the seriousness of an event without 
consultation with the site PI.  
 
12.3 REPORTING OF SAES TO THE SPONSOR AND THE REC 
 
All AEs that are to be reported to the Research Office must be recorded, signed and dated 
by the Investigator at site. Research Office accepts study specific SAE forms, HRA SAE Form 
or RB&HFT template SAE Reporting Form available here.  
 
Information can be submitted in electronic format: 
▪ 
E-mail: research.reporting@rbht.nhs.uk  
▪ 
Fax: 0207 351 8829. 
 
An SAE occurring to a research participant will be reported to the Research Ethics 
Committee (REC) that gave a favorable opinion of the study (the ‘main REC’), the study 
Sponsor (RB&HFT Research Office) and the local R&D Office where in the opinion of the 
CI/PI the event was:   
 
▪ 
‘related’: that is, it resulted from administration of any of the research procedures; 
and  
▪ 
‘Unexpected’: that is, the type of event is not listed in the protocol as an expected 
occurrence.  
 
Reports of related and unexpected SAEs will be submitted within 15 days of the CI/PI 
becoming aware of the event; using the SAE reporting form for non-CTIMPs published on 
the HRA website and entitled non-CTIMP safety report to REC. The form should be 
completed in typescript and signed by the Chief Investigator (CI) prior to submission to the 
REC.  
 
Reports of SAEs in double-blind studies should be un-blinded. 
 
The coordinator of the main REC will acknowledge receipt of safety reports within 30 days. 
It is the responsibility of the CI and his/her research team to send a copy of the SAE 
notification and acknowledgement receipt to the Research Office.    

 
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The research team also has the responsibility to report SAEs occurring in a certain period 
(28 days) after a patient completes the study. Any SAEs reported to the Investigators during 
this phase must be documented in the patient’s medical notes and submitted via an SAE 
form 
 
12.4 THE TYPE AND DURATION OF THE FOLLOW-UP OF SUBJECTS AFTER AES 
The type and duration of follow-up care for subjects following an SAE will be as follows: 6-
12 months following phrenic nerve palsy, valve damage; 3-6 months following vascular 
complications or pericardial effusion (usually these complications are promptly treated 
without major long-term consequence). 
  
12.5 PREGNANCY 
Pregnant patients will be excluded from the study. However, if pregnancy occurs after 
inclusion into the study, we will record and notify pregnancies occurring during the study 
period to the Sponsor.  
Follow-up of pregnant subject:  
• 
No further ablation procedure will be undertaken during the pregnancy period in 
order to avoid radiation exposure and hazards to the foetus.  
• 
Medication contraindicated during pregnancy will be withdrawn.  
• 
No additional investigations involving radiation exposure such as CT, X ray will be 
performed, unless clinically urgent.  
Follow-up of child born to a pregnant trial subject, including male trial subject who is the 
partner of the pregnant woman: 
Children born to a pregnant subject are unlikely to be affected by the participation of the 
parent in the study. For safety reasons, a specialised paediatric team will follow children for 
1 year. 
12.6 ANNUAL PROGRESS REPORTS (APRS) 
The Chief Investigator will prepare the APR for the study. It will be reviewed by the RO and 
sent to the REC by the CI within 30 days of the anniversary date on which the favourable 
opinion was given by the REC, and annually until the study is declared ended. 
 
12.7 REPORTING URGENT SAFETY MEASURES 

 
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The Sponsor and/or the Investigator may take appropriate urgent safety measures in order 
to protect the subjects of a clinical study against any immediate hazard to their health or 
safety. If safety measures are taken, REC approval is not required before the measure is 
taken.  
The Investigator will immediately and in any event no later than 3 days from the date the 
measures are taken, give written notice to the REC and the study Sponsor of the measures 
taken and the circumstances giving rise to those measures. 
In order to prevent any delays in the reporting timelines the Sponsor has delegated this 
responsibility to the CI/PI. Therefore the CI/PI must report any urgent safety measures to 
the REC directly, and in parallel to the Sponsor. The REC coordinator will acknowledge 
receipt of urgent safety measures within 30 days.  
13. 
DATA MANAGEMENT AND QUALITY ASSURANCE 
13.1 CONFIDENTIALITY  
All data will be handled in accordance with the Data Protection Act 1998, NHS Caldecott 
Principles, The Research Governance Framework for Health and Social Care, 2nd Edition 
(2005), and the condition of the REC approval. 
 
The Case Report Forms (CRFs) will not bear the subject’s name or other personal 
identifiable data. The subject’s initials, Date of Birth (DOB) and study Identification Number 
(ID), will be used for identification. 
 
13.2 DATA COLLECTION TOOL  
Case Report Forms (CRF) will be designed by the CI and the final version will be reviewed 
and discussed with the study Sponsor. All data will be entered legibly in black ink with a ball-
point pen.  If the Investigator makes an error, it will be crossed through with a single line in 
such a way to ensure that the original entry can still be read. The correct entry will then be 
clearly inserted. The amendment will be initialled and dated by the person making the 
correction immediately. Overwriting or use of correction fluid will not be permitted. 
 
It is the Investigator’s responsibility to ensure the accuracy of all data entered and recorded 
in the CRFs. The Delegation of Responsibilities Log will identify all study personnel 
responsible for data collection, entry, handling and managing the database. 
 
Data will be firstly recorded into source documents (i.e medical notes) (medical history, 
baseline investigations) and then recorded onto the CRF (with the addition of the procedure 
specific data).  

 
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Methods used to maximise completeness of data will include telephoning subjects who have 
not attended the planned follow-up visit. 
 
13.3 DATA HANDLING AND ANALYSIS 
▪ 
Excel software will be used for data entry. 
▪ 
In order to ensure validity and quality of data we will use cross validation  
▪ 
Data will be stored and backed up on 2 additional hard drives on two different sites 
in order to allow recovery of data in case of a disaster such as fire/flooding/ theft. 
The PI and their collaborators/co-workers will be responsible for data entry and 
quality of data collection. Analysis will be performed by the study investigators and 
reviewed independently of data entry by the statistical team.  
▪ 
Every patient will receive a numerical patient identifier and all data that is transferred 
outside the primary hospital will exclusively be identified by this study number.  
▪ 
The study database will be held at a server at the Royal Brompton Hospital. 
13.4 ARCHIVING ARRANGEMENTS 
The study documents (including the Study Master File (SMF), Case Report Forms (CRFs), 
Informed Consent Forms along with the study database) will be kept for a minimum of five 
years. They will be stored in locked offices within the Royal Brompton and Harefield NHS 
Foundation Trust (RB&HFT). The CI is responsible for the secure archiving of study 
documents. The study database will also be kept electronically on the RB&HFT computer 
network, for a minimum of five years.  
 
The approved repository for longer retention of local materials for studies that involve 
RB&HFT patients is Box-It Storage UK. The study documentation will be prepared for 
archiving by the research team in line with the Research Office Archiving SOP and the 
transfer will be arranged by the Research Office.  
 
Patient anonymised data may be exported for the purpose of offline review and to perform 
the image merge as part of the study and also to further develop the technology.  
 
14. 
STATISTICAL DESIGN 

 
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This is a prospective, non-randomised, observational study which will recruit 15 non-selected 
patients with PVC/VT eligible for catheter ablation, without structural heart disease. 
Procedural outcomes will be compared to age & gender matched procedures of the same 
operator from the last 5 years’ database. 
The statistical design was decided in collaboration with the study PIs and will be descriptive 
only. 
 
14.1 SAMPLE SIZE AND RECRUITMENT 
This is a feasibility pilot study, which will test the feasibility of PVC/VT foci mapping with 
Vivo system and catheter ablation in unselected patients without structural heart disease, 
eligible for PVC/VT ablation. Therefore, no power calculation has been done and the number 
of patient recruited will be of 15 which are deemed sufficient by the CI and Co-PIs on a 
clinical basis. 
 
The estimated recruitment period for the trial will be of 6 months. We estimate that this 
sample size is attainable in practice, as the number of PVC/VT ablation procedures per year 
performed within the Trust is around 100. We also included patients with previous PVC/VT 
ablation in order to maximise chances of recruitment. This pilot is performed with the 
intention to plan a prospective multi-operator/multicentre trial which is adequately powered.  
We will aim to compare the procedure parameters as well as the outcome of this trial to age 
& gender matched procedures of the same operators from the last 5 years’ database.  
 
14.2 ENDPOINTS 
14.2.1 Primary endpoints 
Safety: 
• 
Absence of acute adverse events due to the use of VIVO system during PVC/VT 
ablation 
• 
Safety endpoint of the entire mapping and ablation strategy 
Efficacy: 
• 
To assess the efficacy of VIVO to decrease procedure time as compared to standard 
of care ablation procedures. 
 

 
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14.2.2 Secondary endpoints 
• 
To assess clinical outcome (suppression of reduction of PVCs burden/VT at 3 months 
F/U) 
• 
To assess safety 
• 
To assess economical outcome (cost reduction per case) 
 
14.3 STATISTICAL ANALYSIS PLAN 
Descriptive statistic data with regard to baseline and procedural variables will be reported; 
continuous variables will be expressed by mean ± standard deviation or median and 
interquartile range (25th, 75th percentile), depending on the normality of distribution; 
categorical variables will be summarized by frequencies and percentages. The outcome of 
radiofrequency ablation on the entire cohort of patients will be presented in the form of 
percentage of patients free from symptomatic or documented arrhythmia or with only mild 
symptoms related to arrhythmia recurrence.  
 
Depending on the severity of symptoms and documentation of tachycardia during follow-up, 
patients will be divided into two groups (success/recurrence). Baseline characteristics and 
procedural variables will be compared between these two groups by student t-tests, Mann 
Whitney U tests, or Fisher’s exact test where appropriate in order to identify those variables 
associated with better mid/long term outcomes. A two-tailed p value <0.05 will be 
considered statistically significant. Intra-patient improvement from baseline to 6 months 
follow-up visit will be assessed by McNemar's test. Freedom from PVC/VT will be assessed 
as a time-dependent variable using Cox proportional hazard models.  
 
To judge if ablation strategy using Vivo mapping system is as successful in achieving the 
clinical endpoint, we will compare the procedure parameters as well as the outcome of this 
trial to age & gender matched procedures of the same operator from the last 5 years’ 
database.  
 
To measure the strength of association between the acute successes (PVC/VT suppression 
at the end of the ablation) and outcome, a McNemar test will be performed.  Data will be 
analyzed using SPSS version 18 (IBM Corporation). 
 

 
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14.4 RANDOMISATION 
Not applicable 
14.5 INTERIM ANALYSIS (IF APPLICABLE) 
Not applicable 
14.6 OTHER STATISTICAL CONSIDERATIONS 
None 
15. 
COMMITTEES INVOLVED IN THE STUDY 
 
Trial Management Group (TMG) - normally includes those individuals responsible for the 
day-to-day management of the trial, such as the CI, statistician, trial manager, research 
nurse, data manager. The role of the group is to monitor all aspects of the conduct and 
progress of the trial, ensure that the protocol is adhered to and take appropriate action to 
safeguard participants and the quality of the trial itself. 
 
Monitoring and auditing 
The requirement for study monitoring or audit will be based on the internal Research Office 
risk assessment procedure and applicable Standard Operating Procedures (SOPs). It is the 
responsibility of the RO to determine the monitoring risk assessment and explain the 
rationale to the study research team. 
 
Study monitoring and/or audit will be discussed with the CI before arrangements are made 
to conduct the visit.  
16. 
DIRECT ACCESS TO SOURCE DATA 
The Investigator(s)/institution(s) will permit study-related monitoring, audits, REC review, 
and regulatory inspection(s), providing direct access to source data/documents. Study 
participants are informed of this during the informed consent discussion. Participants will 
consent to provide access to their medical notes. 
17. 
ETHICS AND REGULATORY REQUIREMENTS 
The Sponsor will ensure that the study protocol, Patient Information Sheet (PIS), Informed 
Consent Form (ICF), GP letter and submitted supporting documents have been approved by 
the Health Research Authority (HRA) which includes Research Ethics Committee (REC) 

 
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approval if applicable, prior to any patient recruitment taking place. The protocol and all 
agreed substantial protocol amendments, will be documented and submitted for HRA 
approval prior to implementation. 
 
Before site(s) can enrol patients into the study confirmation of capacity and capability must 
be issued by the institution hosting the trial (unless HRA specifically has confirmed in the 
HRA approval letter that this is not required). It is the responsibility of the PI at each site to 
ensure that all subsequent amendments gain the necessary approvals by the participating 
site. This does not affect the individual clinician’s responsibility to take immediate action if 
thought necessary to protect the health and interest of individual patients. 
Within 90 days after the end of the study, the CI will ensure that the REC is notified that the 
study has finished. If the study is terminated prematurely, those reports will be made within 
15 days after the end of the study. 
 
The CI will supply a final summary report of the clinical study to the REC and the Sponsor in 
parallel within one year after the end of the study.  
 
18. 
FINANCE 
The therapeutic procedure follows the normal clinical pathway for treatment of ventricular 
arrhythmias. The additional cost incurred due to the participation in the Vivo mapping 
protocol per patient will be sponsored by Catheter Precision. In addition, any non-routine 
clinical investigations incurred as part of the clinical protocol will be financially sponsored by 
Catheter Precision. A financial agreement will be in place between Royal Brompton Hospital 
and Catheter Precision to enrolments. 
19. 
INSURANCE AND INDEMNITY 
NHS bodies are liable for clinical negligence and other negligent harm to individuals covered 
by their duty of care. NHS Institutions employing researchers are liable for negligent harm 
caused by the design of studies they initiate. The provision of such indemnity for negligent 
harm should be stated to the participant.  
20. 
PUBLICATION POLICY 
Data ownership rights will lie with the institution. The sponsor agrees that employees of the 
Trust and the investigator, Dr Sabine Ernst, shall be permitted to present at symposia, 
national or regional professional meetings, and to publish in journals, these or dissertation, 
or otherwise of their own choosing, methods and results of the clinical investigation.  

 
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21. 
STATEMENT OF COMPLIANCE 
The trial will be conducted in compliance with the protocol, Sponsor’s Standard Operating 
Procedures (SOPs), GCP and the applicable regulatory requirement(s). 
 
The study conduct shall comply with all relevant laws of the EU if directly applicable or of 
direct effect and all relevant laws and statutes of the UK country in which the study site is 
located including but not limited to, the Human Rights Act 1998, the Data Protection Act 
1998, the Medicines Act 1968, and with all relevant guidance relating to medicines and 
clinical studies from time to time in force including, but not limited to, the ICH GCP, the 
World Medical Association Declaration of Helsinki entitled 'Ethical Principles for Medical 
Research Involving Human Subjects' (2008 Version), the NHS Research Governance 
Framework for Health and Social Care (Version 2, April 2005).    
 
This study will be conducted in compliance with the protocol approved by HRA and 
according to RGF standards. No deviation from the protocol will be implemented without the 
prior review and approval of the Sponsor and HRA except where it may be necessary to 
eliminate an immediate hazard to a research subject. In such case, the deviation will be 
reported to the Sponsor and the REC as soon as possible. 
22. 
LIST OF PROTOCOL APPENDICES 
Appendix 1 Summary Chart of Study Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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23. 
REFERENCES 
 
 
1. Wissner, Erik, et al. Radiofrequency ablation of premature ventricular contractions originating 
from the aortomitral continuity localized by use of a novel noninvasive epicardial and 
endocardial electrophysiology system. Heart Rhythm, (2016); 2, 255-257. 
 
2. Erkapic, Damir, et al. Clinical Impact of a novel three-dimensional electrocardiographic 
imaging for non-invasive mapping of ventricular arrhythmias – a prospective randomized trial. 
Europace (2015); 17, 591-597. 
 
3. Erkapic, Damir, Neumann, Thomas. Ablation of Premature Ventricular Complexes Exclusively 
Guided by Three-Dimensional Noninvasive Mapping. Cardiac Electrophysiology Clinics (2015); 
7, 109-115. 
 
4. van Dam, P., Tung, R., Shivkumar, K., Laks, M. Quantitative localization of premature 
ventricular contractions using myocardial activation ECGI from the standard 12-lead 
electrocardiogram. Journal of Electrocardiology, (2013); 12, 574-579. 
 
5. van Dam, P., Gordon, J.P., Laks, M. Sensitivity of CIPS-computed PVC location to 
measurement errors in ECG electrode position: the need for the 3D Camera. Journal of 
Electrocardiology, (2014); 47, 788-793. 
 
6. Van Dam, P., et al. Electrocardiographic imaging-based recognition of possible induced 
bundle branch blocks during transcatheter aortic valve implantations. Europace (2014); 17, 
750-757. 
 
7. van Dam, P., et al. Development of new anatomy reconstruction software to localize cardiac 
isochrones to the cardiac surface from the 12 lead ECG. Journal of Electrocardiology (2015); 
48 959 – 965. 
 
8. Oosterhoff, P., Meijborg, V., van Dam, P., van Dessel, P., Belterman, C., Streekstra, G. de 
Bakker, J., Ruben, C., Oostendorp. F. Experimental Validation of Noninvasive Epicardial and 
Endocardial Activation Imaging. Circulation Arrhythmia and Electrophysiology, (2016); 9, 
e004104. 
 
9. van Dam, P. et al. Localization of premature ventricular contractions from the papillary 
muscles using the standard 12-lead electrocardiogram: a feasibility study using a novel 
cardiac isochrone positioning system. Europace, (2016); 18, iv16–iv22. 
 
10. Jamil-Copley, Shahnaz, et al. Noninvasive electrocardiographic mapping to guide ablation of 
outflow tract ventricular arrhythmias. Heart Rhythm, (2014); 11, 588-594. 
 
11. Nathani, P., et al. Ventricular Tachycardia in Structurally Normal Hearts: Recognition and 
Management. Supplement of JAPI, (2007); 55, 33-55. 
 
 
 
 
 
 
 

 
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VIVOTM mapping protocol 
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Appendix 1 
Summary chart of study Assessments (Template) 
VIVOTM Mapping Protocol 
Protocol Reference number:  VIVORBH01 Revision A – 15th of January 2019 
Page 37 of 38 
 
 
Please note that the summary chart below should only be used as guidance and ensure that the list of procedures in the chart as well as treatment 
and follow up timelines relate to procedures in your study. 
 
 
 
 
 
 
 
Pre-ablation 
Pre-discharge 
3 months 
12 lead ECG  
 
X  
X  
Telemetry 
X  
 
 
Contrast CT 
scan or non-
contrast CMR 
for roadmap 
X  
 
 
TTE 
 
x  
 
Symptom 
questionnaire 
X  
 
X 
Clinic Visit 
 
 
X  
ECG Holter 
(Mortara) 
X  
 
X  

 
 
VIVOTM Mapping Protocol 
Protocol Reference number:  VIVORBH01 Revision A – 15th of January 2019 
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