Comparison of the Performance of Implantable Cardiac Monitors and Cardiac Implantable Electronic Devices in Detecting Atrial Fibrillation
Phase: NA
Conditions: Atrial Fibrillation
Sponsor: Oxford University Hospitals NHS Trust

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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Comparison of the performance of Implantable Cardiac Monitors and Cardiac Implantable 
Electronic Devices in detecting Atrial Fibrillation (ID-AF) 
 
Internal Reference Number / Short title: ID-AF  
Date and Version No: 3rd August 26th July 20231, version 1.21 
 
Chief Investigator: 
Prof Tim R. Betts MD MBChB FRCP. 
Consultant Cardiologist & Electrophysiologist, Oxford University 
Hospitals NHS Foundation Trust 
Associate Professor, Department of Cardiovascular Medicine, Oxford 
University 
Tel: +44 1865 220256 
Email: tim.betts@ouh.nhs.uk 
 
Investigators:  
Dr Andre Gala MD CCDS MRCP 
Clinical Research Fellow,  
Oxford University Hospitals NHS Foundation Trust 
Tel: +44186520255 
Email: andre.gala@ouh.nhs.uk 
 
Dr Michael Pope, BM CCDS MRCP 
Clinical Research Fellow, 
Oxford University Hospitals NHS Foundation Trust 
Tel: +44186520255 
Email:Michael.pope@ouh.nhs.uk 
 
Dr Milena Leo MD 
Consultant Cardiologist 
Oxford University Hospitals NHS Foundation Trust 
Tel: +44186520255 
Email:milena.leo@ouh.nhs.uk 
 
Dr Richard Varini MBBS MRCPI 
Clinical Research Fellow,  
Oxford University Hospitals NHS Foundation Trust 
Tel: +44186520255 
Email: richard.varini@ouh.nhs.uk 
 
 
 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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Sponsor:  
Oxford University Hospitals NHS Foundation Trust 
Headley Way, Headington, Oxford (OX3 9DU) 
 
 
Funder:  
 
 
 
 
Chief Investigator signature:     
 
Cardiac Rhythm Research Hub (Oxford University Hospitals) 
Abbott Medical Grant 
Medtronic  Grant 
 
 
 
Potential Conflicts of Interest: Consumables for this study were funded with industry support (Abbott 
and Medtronic) and one of the co-investigators (A.G) received salary support from an Abbott grant. 
Conflicts of interest will be declared in all work derived for this study. Abbott and Medtronic were not 
involved in study design and drafting the protocol and will not be involved in data collection and data 
analysis. 
 
 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to anyone other than the 
Sponsor, the Investigator Team, HRA, host organisation, and members of the Research Ethics Committee 
and Regulatory Authorities unless authorised to do so. 
 
 
 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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TABLE OF CONTENTS 
1. 
KEY TRIAL CONTACTS............................................................................................................................ 5 
2. 
LAY SUMMARY ..................................................................................................................................... 6 
3. 
SYNOPSIS .............................................................................................................................................. 7 
4. 
ABBREVIATIONS ................................................................................................................................... 9 
5. 
BACKGROUND AND RATIONALE ......................................................................................................... 10 
6. 
OBJECTIVES AND OUTCOME MEASURES ............................................................................................ 11 
7. 
STUDY DESIGN .................................................................................................................................... 13 
8. 
PARTICIPANT IDENTIFICATION ........................................................................................................... 14 
8.1. 
Trial Participants ......................................................................................................................... 14 
8.2. 
Inclusion Criteria ......................................................................................................................... 14 
8.3. 
Exclusion Criteria ........................................................................................................................ 15 
8.4. 
Recruitment ................................................................................................................................ 15 
8.5. 
Informed Consent ....................................................................................................................... 15 
8.6 
Screening and Eligibility Assessment .......................................................................................... 16 
8.7 
Randomisation............................................................................................................................ 16 
8.8 
Blinding ....................................................................................................................................... 17 
8.9 
Baseline Assessments ................................................................................................................. 17 
8.11 Early Discontinuation/Withdrawal of Participants ......................................................................... 18 
9 
TRIAL INTERVENTIONS........................................................................................................................ 19 
9.1 
Other Interventions .................................................................................................................... 19 
10 
SAFETY REPORTING ........................................................................................................................ 19 
10.1 
Definition of Serious Adverse Events .......................................................................................... 19 
10.2 
Reporting Procedures for Serious Adverse Events ..................................................................... 19 
11 
STATISTICS AND ANALYSIS .............................................................................................................. 20 
11.1 Sample size calculation ....................................................................................................................... 20 
12 
DATA MANAGEMENT ..................................................................................................................... 20 
12.1 
Source Data ................................................................................................................................ 20 
12.2 
Access to Data ............................................................................................................................ 20 
12.3 
Data Recording and Record Keeping .......................................................................................... 21 
13 
QUALITY ASSURANCE PROCEDURES ............................................................................................... 21 
13.1 
Risk assessment .......................................................................................................................... 21 
13.2 
Study monitoring ........................................................................................................................ 21 
13.3 
Study Committees ...................................................................................................................... 22 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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14 
PROTOCOL DEVIATIONS ................................................................................................................. 22 
15 
SERIOUS BREACHES ........................................................................................................................ 22 
16 
ETHICAL AND REGULATORY CONSIDERATIONS .............................................................................. 22 
16.1 
Declaration of Helsinki ................................................................................................................ 22 
16.2 
Guidelines for Good Clinical Practice .......................................................................................... 22 
16.3 
Approvals .................................................................................................................................... 22 
16.4 
Reporting .................................................................................................................................... 23 
16.6 
Participant Confidentiality .......................................................................................................... 23 
16.7 
Expenses and Benefits ................................................................................................................ 23 
17 
FINANCE AND INSURANCE.............................................................................................................. 23 
17.1 
Funding ....................................................................................................................................... 23 
17.3 
Contractual arrangements .......................................................................................................... 24 
18 
PUBLICATION POLICY...................................................................................................................... 24 
19 
DEVELOPMENT OF A NEW PRODUCT/ PROCESS OR THE GENERATION OF INTELLECTUAL 
PROPERTY ................................................................................................................................................... 24 
20 
ARCHIVING ..................................................................................................................................... 24 
21 
REFERENCES ................................................................................................................................... 24 
22 
APPENDIX A:  STUDY FLOW CHART ................................................................................................ 26 
23 
APPENDIX B:  SCHEDULE OF STUDY PROCEDURES ......................................................................... 27 
24 
APPENDIX C:  AMENDMENT HISTORY ............................................................................................ 28 
 
 
 
 
 
 
 
 
 
 
 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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1. KEY TRIAL CONTACTS 
 
Chief Investigator 
Dr Tim R. Betts MD MBChB FRCP. 
Consultant Cardiologist & Electrophysiologist, Oxford University 
Hospitals NHS Foundation Trust 
University Research Lecturer, Department of Cardiovascular Medicine, 
Oxford University 
Tel: +44 1865 220256 
Email: tim.betts@ouh.nhs.uk 
 
Sponsor 
Oxford University Hospitals NHS Foundation Trust 
Headley Way, Headington, Oxford OX3 9NU 
Funder(s) 
Cardiac Rhythm Research Hub (Oxford University Hospitals) 
Abbott Medical 
Medtronic Grant 
Clinical Trials Unit 
 
Committees 
 N/A 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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2. LAY SUMMARY  
Atrial fibrillation (AF) is the most common abnormal heart rhythm disturbance, affecting 1-2 million 
people in the UK. The irregular heartbeat caused by AF can make the heart pump blood less efficiently. 
This may lead to small blood clots forming inside the heart that, if they were to breakaway, can lead to 
blockage of small blood vessels. As a result, AF significantly increases the risk of having a stroke, heart 
failure and dementia.  Despite having AF, a significant proportion of people have no symptoms, and they 
may be only found to be in AF after having a stroke. Therefore, diagnosis largely relies on accurate ECG 
monitoring. 
AF episodes can be unpredictable, of very short duration and easily missed unless continuous ECG 
monitoring is undertaken. Pacemakers can continuously record the heart’s electrical activity and detect 
AF with a high degree of confidence. However, they are invasive and rely on electrical wires implanted 
inside the heart, and hence less suited to be used as primary monitoring devices. To overcome these 
difficulties, implantable cardiac monitors (ICM) have been designed to be placed under the skin. 
The new generation of ICMs has been miniaturised and are can now be injected under the skin. 
Moreover, they connect with the patient’s smartphone and which can used to annotate symptoms and 
send ECG recording to their doctor when experiencing symptoms. Previous generation of ICMs could 
only transmit once a day (at night) and require close proximity to a home-based stationary monitor. This 
resulted in frequent failed transmission and delays from arrhythmic episodes detected by ICM and 
transmission to their physician. 
Despite these significant improvements, their ability to reliably capture AF has never been tested against 
pacemakers. 
The aim of this project is to study the performance of the two commonly used ICMs in detecting AF 
episodes and explore how the new connectivity can empower patients and improve patient care. We 
plan to inject an ICM in 30 patients with AF and pre-existing pacemaker. After a period of 6 months, we 
will compare how many episodes were detected in each device. With the information collected we will 
try to understand the pitfalls in the current technology and develop strategies to improve it.  
Accurate, minimally-invasive long-term ECG monitoring can have far reaching benefits for patients, both 
in routine clinical practice and research. It can help identify AF in patients that have had an unexplained 
stroke, it can aid doctors’ decisions in patients with infrequent but severe symptoms and monitor 
response to treatment. Furthermore, it is an important research tool that may provide more insight into 
the natural history of the disease and reliably test the efficacy of new drugs and procedures. 
 
 
 
 
 
 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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3. SYNOPSIS 
 
Trial Title 
Comparison of the performance of Implantable Cardiac Monitors and 
Cardiac Implantable Electronic Devices in detecting Atrial Fibrillation  
Internal ref. no. (or 
short title) 
ID-AF 
Trial registration 
Intended register – Clinicaltrials.gov  
Sponsor  
Oxford University Hospitals NHS Foundation Trust  
 
Funder  
Cardiac Rhythm Research Hub (Oxford University Hospitals) 
Abbott Medical 
Medtronic  
Clinical Phase  
Pilot study 
Trial Design 
Prospective, single centre, randomised observational study. 
Trial Participants 
Male and female adults with a dual-chamber CIED with a functioning 
atrial lead and Paroxysmal or Persistent Atrial Fibrillation 
Sample Size 
30 subjects (15 on each investigation arm) 
Planned Trial Period  
15 monthsExtension of study end date until 30th June 2024 
Planned Recruitment 
period  
3 – 6 monthsExtension of recruitment period until 31st December 2023 
 
Objectives 
Outcome Measures 
Timepoint(s)  
Primary 
 
Primary Objective 
 
1. 
To 
compare 
the 
performance 
of 
the 
Confirm Rx™ ICM and 
Reveal LINQ™ ICM in 
detecting 
clinically 
significant AF episodes 
(episodes longer than 6 
minutes) to CIED (gold 
standard). 
 
1. 
Confirm 
Rx 
and 
Reveal 
LINQ™ 
ICM 
sensitivity, 
specificity, 
positive predictive value 
and negative predictive 
value will be calculated 
for AF episodes longer 
than 6 minutes  
 
 
 
During 
follow-up (6 
months) 
Secondary 
 
Secondary Objectives 
 
1. 
To 
compare 
the 
changes 
in 
R-wave 
amplitude 
following 
implantation 
in 
both 
ICMs. 
2. 
To 
compare 
the 
transmission success rate 
 
1. 
Compared 
the 
percentage of changes 
in R-wave amplitude 
between both ICMs 
 
2. The percentage of 
successful transmission 
in both ICMs will be 
calculated. 
 
 
1. 
During 
the 
follow-
up period (6 
month) 
 
 
2. 
During 
the 
follow-
up period (6 
month) 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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of both devices. 
 
3. To compare between 
both devices the number 
of 
patient- 
activated 
recordings that contains 
symptoms  attributed to 
those episodes.  
 
 
3. The percentage of 
activated 
recordings 
with symptoms will be 
calculated.  
   
 
 
 
 
3. 
During 
follow-up 
period 
(6 
months) 
 
Intervention(s) 
• 
Medical Device 
  
 
Implantable cardiac monitors (ICM): Confirm Rx™ (Abbott) and Reveal 
LINQ™(Medtronic) 
  
Comparator  
Cardiac 
Implantable 
Electronic 
Devices 
(Pacemakers, 
Cardiac 
resynchronisation therapy, Implantable cardioverter-defibrillator) with 
a functioning atrial lead 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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4. ABBREVIATIONS 
 
AE 
Adverse event 
AF 
Atrial fibrillation 
AR  
Adverse Reaction 
AT 
Atrial Tachycardia 
CI 
Chief Investigator 
CIED 
Cardiac Implantable Electronic Device 
CRF 
Case Report Form 
CRT 
Cardiac Resynchronisation therapy 
CT 
Clinical Trials 
CTA 
Clinical Trials Authorisation 
CTRG 
Clinical Trials and Research Governance 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
HRA 
Health Research Authority 
IB 
Investigators Brochure 
ICD 
Implanted Cardioverter-Defibrillator 
ICM 
Implanted Cardiac Monitor 
ICF 
Informed Consent Form 
IRB 
Independent Review Board 
NHS 
National Health Service 
RES 
 Research Ethics Service  
PI 
Principal Investigator 
PIL 
Participant/ Patient Information Leaflet 
R&D 
NHS Trust R&D Department 
REC 
Research Ethics Committee 
RSI 
Reference Safety Information  
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
TMF 
Trial Master File 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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5. BACKGROUND AND RATIONALE 
 
Clinical significance: Atrial fibrillation (AF) is the most common sustained arrhythmia affecting millions of 
people worldwide, leading to significant morbidity and mortality. [1] It is associated with a 5-fold increase 
risk of ischaemic stroke[2], accounting for 20-25% of all strokes which are generally more severe and 
disabling than non-AF related strokes.[3] In addition, patients with AF have a 3-fold increase in heart 
failure and 2- fold increase in dementia.[4]  
Although the exact duration of AF required to cause a thromboembolic stroke is not known, episodes 
longer than 6 minutes detected by a CIED have been shown to increase the risk of stroke[5]. Significant 
morbidity is associated with the duration and total burden of AF.[6, 7]  Nonetheless, a large proportion of 
patients remains asymptomatic despite being in AF. [8] In pacemaker patients, only 21% reported 
symptoms during AF episodes that were recorded by their device.  [9] In addition, the perception of AF 
related symptoms may change following an AF ablation with a 2-5 fold increase in the number of 
asymptomatic AF episodes. [10, 11] Thus, symptoms alone are unreliable in identifying the presence or 
absence of AF. Consequently, ECG monitoring tools play a critical role in the documentation of AF.   
ECG monitoring: There is a correlation between the duration and intensity of ECG monitoring and the 
detection of AF, with continuous long-term ECG monitoring being superior to intermittent monitoring.[11]  
Continuous long-term ECG monitoring can be performed either intracardiac, with cardiac implantable 
electronic devices (CIED), or subcutaneously, with implantable cardiac monitors (ICM). 
Dual-chamber cardiac implantable electronic devices (CIED): Pacemakers, ICDs, CRTs have excellent AF 
diagnostic capability with high sensitivity and specificity.[12-14] The atrial lead is in direct contact with the 
atrial myocardium and generates high quality intracardiac electrograms (EGM) that are interpreted by 
advanced AF algorithms.  However, the invasive nature of the procedure, potentially serious long-term 
complications, and high cost make them an inadequate primary arrhythmia monitoring device. Yet, in 
patients with pre-existing CIEDs, they can be used as a ‘gold-standard’ AF detection monitor to validate 
other devices.[14]   
First generation implantable cardiac monitors (ICM) were implanted subcutaneously, using blunt 
dissection, in the catherisation laboratory. Their AF detection algorithm was rudimentary, relying solely 
on irregular R-R intervals measurements. As a result, they were prone to false positive results caused by 
artefact and other irregular rhythms such as ventricular ectopy. The SMJ Confirm™ ICM had a sensitivity 
of 94% but a positive predictive value of only 64% for detection of clinically significant AF episodes 
(longer than 6 minutes).[15] Furthermore, all ICMs transmissions to the Clinician’s Web Portal required 
the subject to be within 2 metres of the home transmitter which resulted in suboptimal transmission 
success.   
 
New generation Implantable cardiac monitors (ICM):  They offer a minimally invasive approach for 
continuous ECG monitoring. ICMs outperform the external ambulatory ECG in the diagnosis of clinically 
significant arrhythmias in patients presenting with palpitations, syncope, cryptogenic stroke and post-AF 
ablation. [16, 17]. AF detection relies on a two-step approach. Firstly, they identify irregular R-R intervals 
and either a Markov chain model or Lorenzo plot to assign an AF probability score. Secondly, they review 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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the electrograms for any evidence of P waves. If no P waves are detected it is logged as AF.  The two ICM 
to be studied are: 
 
Reveal LINQ™ ICM (Medtronic™):  Commonly used ICM with reported high sensitivity and positive 
predicted value. However, its AF algorithm has never been validated against CIED. Transmissions are 
performed through a home-monitor,  20% of which are unsuccessful l[4]. The most current version can 
use a smartphone app (Medtronic™) and Bluetooth® connection to transmit the recording, however the 
transmission success rate has not been studied.  
 
Confirm Rx™ ICM X (Abbott™): Was the first ICM equipped with Bluetooth® wireless technology that 
connects directly with the patient’s smartphone via the myMerlin™ app (Abbott™). The myMerlin™ app 
features include activation of ECG recordings when experiencing symptoms, viewing of transmission 
history to confirm successful data transfer and receiving notifications for scheduled transmission and 
device checks. Neither the AF algorithm nor the myMerlin App have been independently validated.  
 
Only CE-marked devices and respective smartphone apps will be used in this trial . 
 
Future direction: 
Injectable technologies have a large potential to improve the management of patients with AF, both as a 
diagnostic tool but also to guide therapies. However, its utility is dependent on having very sensitive, 
reasonably specific detection of clinically relevant AF episodes and high transmission success. This pilot 
study will investigate the accuracy of the new generation ICM and lay the foundation for future trials 
using different management strategies will be guided by ICM recordings and alerts from smartphone 
apps.  
 
5. 1 Hypothesis 
Injectable and wearable technologies have huge potential to improve the management of patients with 
AF, both as a diagnostic tool but also to guide therapies. “As-needed” use of oral anticoagulants has been 
proposed as a cost-effective way to prevent thromboembolic stroke as well as increasing patient 
compliance and satisfaction. However, its utility is dependent on having very sensitive, reasonably 
specific detection of clinically relevant AF episodes and high transmission success. It is therefore 
important to determine how accurate the latest devices and their detection algorithms are when 
compared to the gold standard of CIEDs (pacemakers, implantable cardiac defibrillators (ICD) and cardiac 
resynchronisation therapy (CRT) devices) that have atrial leads and constant monitoring 
We hypothesize that the new generation ICMs (Confirm Rx™ and Reveal LINQ™) can identify the majority 
(sensitivity above 95%, positive predictive value above 85%) of clinically significant AF episodes (longer 
than 6 minutes). We also estimate that with Bluetooth® technology connecting to patients’ smartphone 
will improve the transmission success rate above 80%.  
6. OBJECTIVES AND OUTCOME MEASURES 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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Objectives 
Outcome Measures  
Timepoint(s) 
of 
evaluation 
of 
this 
outcome measure (if 
applicable) 
Primary Objective 
1. To compare the performance of 
the Confirm Rx™ ICM and Reveal 
LINQ™ ICM in detecting clinically 
significant AF episodes (episodes 
longer than 6 minutes) to cardiac 
implantable electronic devices 
(CIED). 
 
 
 
1. Confirm Rx and Reveal LINQ™ 
ICM sensitivity, specificity, positive 
predictive 
value 
and 
negative 
predictive value will be calculated 
for AF episodes longer than 6 
minutes  
 
 
During follow-up (6 
months) 
Secondary Objectives 
1. To compare changes in the 
recording of electrograms (heart's 
electrical 
activity) 
R- 
wave 
amplitude from time of implant to 
end of follow-up (6 months) 
2. To compare the transmission 
success rate of episodes recorded 
by 
the 
implantable 
cardiac 
monitors to the Clinician's Web 
Portal. 
 
3. To compare between both 
devices the number of patient- 
activated recordings that contains 
symptoms \\cts attributed to those 
episodes  
 
1. Compared the percentage of 
changes 
in 
R-wave 
amplitude 
between both ICMs 
 
 
2. The percentage of successful 
transmission in both ICMs will be 
calculated. 
 
 
 
3. The percentage of activated 
recordings with symptoms will be 
calculated. 
 
1. During the follow-
up period (6 month) 
 
 
2. During the follow-
up period (6 month) 
 
 
3. During follow-up 
period (6 months) 
 
Exploratory Objectives 
1. To study the changes in P-wave 
amplitude 
between 
different 
positions in the chest. 
 
1. Percentage of change in P and R-
wave amplitudes between V1 and V2 
position. Percentage of change in P and 
R-wave amplitudes between surface 
 
1. During implant 

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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and subcutaneous electrograms. 
 
7. STUDY DESIGN 
 
The ID-AF study is a prospective, single centre, randomised observational study aimed at comparing the 
performance of the Confirm Rx™ and Reveal LINQ™ ICMs in the detection of clinically relevant atrial 
fibrillation (AF) episodes to cardiac implantable electronic devices (CIED) 
Subjects with pre-existing cardiac implanted electronic devices (Pacemakers, CRT and ICD devices) who 
have remote monitoring ability and are able to record electrograms will be identified by interrogation of 
the John Radcliffe Hospital Pacemaker Database. Subjects with a functioning atrial lead, on remote 
monitoring, non-permanent AF with an AF burden of more >2% in the last year will be invited to 
participate. Those who have expressed an interest in participating will be invited for an initial interview 
(eligibility assessment, baseline assessment and informed consent). 
This study will randomise 30 subjects to receive either a Confirm Rx™ ICM or a Reveal LINQ™ ICM. The 
ICM will be implanted in the Outpatient setting as a Day Case Procedure according to manufacturer 
instructions. Prior to the implant, 2 minutes of recording in V1 and V2 position with the surface ICM 
mapping will be performed. The R-wave amplitude will be recorded at the end of the procedure. Subjects 
will be taught how to use the home-based transmitter and mobile app.  
As it is standard of care, the research team will book a telephone follow-up appointment at 4-6 weeks to 
address any questions the subjects may have regarding the ICM, review ICM battery and wound. The 
ICMs are programmed for automatic daily transmissions of the recorded episodes to the Clinician’s Web 
Portal. Scheduled remote transmissions for CIED will be performed at least monthly. At 6 months, 
subjects will be invited to attend a Device Clinic appointment for the final download from both devices. 
At this time, they may choose to have the ICM removed or left in-situ but turned off. During this last visit, 
ICM transmissions log will be interrogated. The end of the study for each patient will be the date of the 6 
months follow-up appointment.  
7.1 Study Timeline 
This 15-month single centre, randomised observational study is to be conducted in 3 phases: 
1. Start-up period (3 months): to finalise and submit the REC form, to screen the CIED database for 
potential participants with high burden and/or episodes of AF. 
2. Patient recruitment, ICM implant and data entry (9 months): during this period recruitment will 
take place and the confirm Rx will be implanted. Data entry to be completed within 6 weeks of 
enrolment and will be monitored every 2 months.  
3. Completion of data entry and analysis (3 months): to finalise the data entry, adjudicate all 
electrograms and perform the statistical analysis. A final wrap up meeting will be convened at 
the end of the study with all key investigative staff contributing to the final report and 
manuscript.  

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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       7.2 Study Risks 
The Confirm Rx™ ICM and the Reveal LINQ™ ICM implant procedure is safe and minimally invasive. They 
are both have CE marking and having been used in routine clinical practice for several years. The 
procedure will be performed under sterile conditions and local anaesthetic using the insertion tools 
supplied by the manufacturer. They have very similar implant techniques and they are both injected 
subcutaneously in the anterior chest wall. 
There are no known contraindications. Potential adverse events include: 
• 
bruising,  
• 
haematoma (<1%),  
• 
superficial infection (<1%),  
• 
keloid formation,  
• 
migration 
• 
extrusion.  
 
 
  
      7.3 Study Benefits 
Patient could get direct benefit from the study if the ICM is able to record arrhythmias that were not 
capture by the CIED. However, the main benefits from this study will be for future patients. It is 
important to understand how well the AF detection algorithms of these new generation ICM perform in 
comparison to the gold standard CIED. Furthermore, it will provide an opportunity to understand the 
pitfalls of the AF the current AF diagnostic algorithms and inform future optimisations.  
8. PARTICIPANT IDENTIFICATION 
8.1. Trial Participants 
This trial is designed to include male and female adults with a dual-chamber CIED with a functioning 
atrial lead and Paroxysmal or Persistent Atrial Fibrillation.  
8.2. Inclusion Criteria 
The participant must satisfy the following conditions: 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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• 
Participant is willing and able to give informed consent for participation in the trial. 
• 
Male or Female aged 18 years or above. 
• 
History of paroxysmal and persistent AF  
• 
Dual-chamber pacemaker, ICD or CRT device with a functioning atrial lead, able to record 
electrograms and remote monitoring.  
8.3. Exclusion Criteria 
The participant may not enter the trial if ANY of the following apply: 
• 
Diagnosis of permanent AF. 
• 
Contra-indications for implantable cardiac monitor. 
• 
Unable to comply with the follow-up schedule. 
8.4. Recruitment 
Potential participants with a Cardiac Implanted Electronic Devices (Pacemakers, CRT and ICD) with a 
functioning atrial lead will be selected in Outpatient Pacemaker Clinics, Remote Pacemaker Clinics and 
hospital pacemaker database by the OUH NHS Trust Cardiac Rhythm Management Team. All members of 
the research team are part of the Cardiac Rhythm Management Care Team.  Patients will be invited to 
participate in the study if there is presence of high AF burden or frequent AF episodes in a device 
download within the last year. 
A letter of invitation, a patient information brochure and a consent form will be given to potential 
participants at the time of the Outpatient Clinic.  In the Remote Pacemaker Clinic, as potential 
participants are not physically present, a letter of invitation and patient information brochure will be 
sent by post if they have non-permanent AF in their most recent transmission. Upon receiving and 
considering the information participants can use the contact the Arrhythmia Research Team by email or 
telephone to request more information or to express their interest in being enrolled.  
If they wish to participate a baseline visit will be organised which will include informed consent, 
screening, and eligibility assessment. 
8.5. Informed Consent 
The participant must personally sign and date the latest approved version of the Informed Consent form 
before any trial specific procedures are performed. 
Written and verbal versions of the Participant Information and Informed Consent will be presented to 
the participants detailing no less than: the exact nature of the trial; what it will involve for the 
participant; the implications and constraints of the protocol; the known side effects and any risks 
involved in taking part. It will be clearly stated that the participant is free to withdraw from the trial at 

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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any time for any reason without prejudice to future care, without affecting their legal rights and with no 
obligation to give the reason for withdrawal. 
The participant will be allowed as much time as wished to consider the information, and the opportunity 
to question the Investigator, their GP or other independent parties to decide whether they will 
participate in the trial. Written Informed Consent will then be obtained by means of participant dated 
signature and dated signature of the person who presented and obtained the Informed Consent. The 
person who obtained the consent must be suitably qualified and experienced and have been authorised 
to do so by the Chief/Principal Investigator. A copy of the signed Informed Consent will be given to the 
participant and another copy will be filed in the notes The original signed form will be retained at the 
trial site. 
 
8.6 Screening and Eligibility Assessment 
If a subject meets the inclusion criteria they will be invited to participate in the study. The inclusion 
criteria are based on the pacemaker interrogation performed in clinic.  
After agreeing to participate and signing the consent form, the following data will be collected: 
1. Demographics (age, gender, ethnicity) 
2. Detailed collection of medical history which should include atrial fibrillation history, previous 
cardiac procedure (cardiac surgery, atrial fibrillation ablation, direct current cardioversion), 
significant co-morbidities 
3. Imaging data recorded previously as part of standard clinical practice: left ventricular systolic 
function, diastolic function, evidence of valvular heart disease, cardiac chamber size.  
4. Current medications 
5. Height, weight and BMI 
6. Current CIED name, model, implant indication 
 
8.7 Randomisation 
A block randomisation with block size of 2 will be used to assign each study subject with an ICM. There 
are two investigation arms in this study: 
• 
Group A: Confirm Rx™ 
• 
Group B: Reveal LINQ™ 
As this study will enrol a total of 30 patients there will be 3 blocks of 10 patients each. In each block, 
subjects will be randomised to either Group A or Group B; therefore, at the end of each block there will 
be 5 subjects in each investigation arm. Randomisation will be performed during the baseline visit. A 
telephone call will be made to the research office and an envelope from the current block of 10 with the 
investigation of arm letter will be opened.   

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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8.8 Blinding  
Investigators and subjects will not be blinded to investigation arm. 
 At the end of follow-up, the CIED and ICM electrograms catalogued by the devices as AF will be 
adjudicated by two electrophysiologists blinded to patient data.  
8.9 Baseline Assessments 
Baseline assessment will include:  
1. Detailed collection of medical history which should include atrial fibrillation history, previous 
cardiac procedure (cardiac surgery, atrial fibrillation ablation, direct current cardioversion), 
significant co-morbidities 
2. Imaging data recorded previously as part of standard clinical practice: left ventricular systolic 
function, diastolic function, evidence of valvular heart disease, cardiac chamber size.  
3. Current medications 
4. Height, weight and BMI 
8.9.1 Intervention – ICM implant (Confirm Rx™ or Reveal LINQ™) 
The Confirm Rx™ ICM or Reveal LINQ™ ICM will be implanted as a Day Case. Prior to implant, recording 
of surface electrograms will be performed in V1 and V2 position to assess P and R-wave amplitudes. The 
procedure will be performed under sterile conditions and local anaesthetic (lidocaine 1%) using the 
insertion tools supplied by the manufacturer. They have very similar implant techniques and they are 
both injected subcutaneously in the anterior chest wall. If there is suboptimal R wave amplitude the 
operator can reposition the device. The subject will be premedicated with intravenous antibiotics as per 
Trust Policy to reduce the risk of infection. The operator may choose to close the wound with steri-strips, 
glue or a suture. 
At the end of the procedure the R-wave amplitude will be recorded. Subjects will be taught how to use 
the mobile apps or the home-based monitor, depending on the device. They will be able to initiate 
recordings, send transmission and record their symptoms 
 The CIED will be programmed to record 
any AT/AF and save the electrogram for future adjudication. The CIED and ILR date and time clocks will 
be synchronized. 
The Confirm Rx™ ICM and the Reveal LINQ™ ICM implant procedure is safe and minimally invasive. There 
are no known contraindications. Potential adverse events include bruising, haematoma, superficial 
infection, keloid formation, migration or extrusion.  
 
The LINQ™ and the Confirm Rx™ only transmit recordings to their company’s servers (Carelink™, for 
Medronic; Merlin.net™, for Abbott) via their respective smartphone app or homebased monitor.  ICM 
recordings can only be accessed on these servers by using the clinician web portal. The assigned trial 
specific ID number will be used to register the device in the Carelink (for Medtronic devices) and 
Merlin.net (for Abbott devices); thus, no identifiable patient information will be in the servers. Access to 
these servers is via the clinician web portal is password protected. Transmission reports will be 
downloaded from the Medtronic™ and Abbott™ servers and stored in password protect excel 
spreadsheet that will only be used in OUH trust computers.  

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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        8.10 Subsequent Visits 
        8.10.1 Scheduled Remote ICM and CIED Transmissions 
Scheduled monthly remote ICM and CIED transmissions will be performed. Electrograms catalogued as 
AF episodes by the both devices will be downloaded for analysis from the clinicians web portal where the 
data is safely stored in Medtronic™ and Abbott™ server as it standard practice.  All transmissions will be 
anonymous and only identified by the trial ID number. 
If due to technical difficulties remote download is not possible subjects will be invited to attend 
Pacemaker Clinic for a download. 
       8.10.2 Visits 
Visit 1: As is standard of care, Telephone Clinic review at 4-6 weeks after the ICM implant to review the 
wound, check performance and battery of ICM. 
Visit 2: At 6 months, subjects will attend Device Clinic for a final download of both devices and at this 
time, they may choose to have the ICM removed. An updated drug history will be recorded. 
8.11 Early Discontinuation/Withdrawal of Participants  
During the course of the trial a participant may choose to withdraw early from the trial treatment at any 
time.  This may happen for a number of reasons, including but not limited to:   
• 
The occurrence of what the participant perceives as an intolerable AE.   
• 
Inability to comply with trial procedures  
• 
Participant decision  
• 
Loss to follow-up 
 
Participants may choose to withdraw from study assessments but may remain on study follow-up.  
Participants may also withdraw their consent, meaning that they wish to withdraw from the study 
completely. 
In addition, the Investigator may discontinue a participant from the trial treatment at any time if the 
Investigator considers it necessary for any reason including, but not limited to: 
• 
Pregnancy 
• 
Ineligibility (either arising during the trial or retrospectively having been overlooked at screening) 
• 
Significant protocol deviation 
• 
Significant non-compliance with treatment regimen or trial requirements 
• 
Disease progression which requires discontinuation of the trial medication or results in inability 
to continue to comply with trial procedures                                                                                                                           
The type of withdrawal and reason for withdrawal will be recorded in the CRF.  
In case of withdrawal from the study in an early stage (before intervention), the patient data will be 
excluded from the analysis and a new participant will be enrolled.  

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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If the participant is withdrawn due to an adverse event, the Investigator will arrange for follow-up visits 
follow-up visits or telephone calls until the adverse event has resolved or stabilised. 
If the participant withdraws, he may choose to: 
• 
Continue to have the routine ICM (Confirm Rx™ or LINQ™) downloads as per clinical need 
• 
To have the ICM (Confirm Rx™ or LINQ™)) turned off. 
• 
Have the ICM (Confirm Rx™ or LINQ™)) removed. The investigators will organise an outpatient 
procedure.   
8.12 Definition of end of study 
The end of the study will be the date of the last 6 month Confirm Rx™ ICM or LINQ™ ICM and CIED report 
download. 
9 TRIAL INTERVENTIONS  
9.1 Other Interventions 
No other interventions will be performed except for the ICM implant and, at the end of the trial, if the 
subject wishes, ICM explant (see 8.9.1) 
10 SAFETY REPORTING  
10.1 
Definition of Serious Adverse Events 
A serious adverse event is any untoward medical occurrence that: 
• 
results in death 
• 
is life-threatening 
• 
requires inpatient hospitalisation or prolongation of existing hospitalisation 
• 
results in persistent or significant disability/incapacity 
• 
consists of a congenital anomaly or birth defect. 
Other ‘important medical events’ may also be considered a serious adverse event when, based upon 
appropriate medical judgement, the event may jeopardise the participant and may require medical or 
surgical intervention to prevent one of the outcomes listed above. 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in which the 
participant was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it were more severe. 
10.2 
Reporting Procedures for Serious Adverse Events 
A serious adverse event (SAE) occurring to a participant should be reported to the REC that gave a 
favourable opinion of the study where in the opinion of the Chief Investigator the event was ‘related’ 
(resulted from administration of any of the research procedures) and ‘unexpected’ in relation to those 

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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procedures. Reports of related and unexpected SAEs should be submitted within 15 working days of the 
Chief Investigator becoming aware of the event, using the HRA report of serious adverse event form. 
11 STATISTICS AND ANALYSIS 
 
11.1 Sample size calculation 
The largest study to date using ICMs was performed in 1049 patients with known AF which were 
followed for 3 months. AF episodes longer than 6 minutes were seen in 53% of patients who had, on 
average, 7 AF episodes per month. We will recruit patients with known high frequency of AF episodes 
therefore we can assume AF episodes in least 40% of patients during the 6 months study period.  
Using the Buderer’s formula, 327 episodes of AF are required if the expected AF detection algorithm 
sensitivity is 95% and the specificity is 85% with a 95% confidence interval. Therefore, with a rate of 7 
episodes per month a minimum of 8 subjects for each ICM is needed.  We will aim to recruit 30 
patients so that a broad spectrum of patient characteristics can be accounted for. 
 
       11.2 Analysis of Outcome measures 
Descriptive statistics are reported as count and percentage for categorical variables and mean and 
standard deviation for continuous variables. 
The ICM performance will be investigated by calculating the sensitivity, specificity, positive predictive 
value and negative predictive value of AF episodes longer than 6 minutes will be calculated 
12 DATA MANAGEMENT 
12.1 
Source Data 
Source documents are where data are first recorded, and from which participants’ CRF data are 
obtained. These include, but are not limited to, hospital records (from which medical history and 
previous and concurrent medication may be summarised into the CRF), clinical and office charts, 
laboratory and pharmacy records, diaries, microfiches, radiographs, ICM and CIED reports and 
correspondence. 
CRF entries will be considered source data if the CRF is the site of the original recording (e.g. there is no 
other written or electronic record of data).  All documents will be stored safely in confidential conditions. 
On all study-specific documents, other than the signed consent, the participant will be referred to by the 
study participant ID number, not by name. 
12.2 
Access to Data 
Direct access will be granted to authorised representatives from the Sponsor and host institution for 
monitoring and/or audit of the study to ensure compliance with regulations. 

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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12.3 
Data Recording and Record Keeping 
The participants will be identified by a unique trial specific ID number which will be assigned following 
consent. The trial ID number will be used in both hard-copies and electronic documents. The hard copies 
(CRF and consent forms) of data will be securely kept in the Research Fellows’ Office located in the John 
Radcliffe Hospital, Level 2 Blue Outpatients.  
The key to the trial specific ID number will be maintained on a single document will be kept on a 
separate folder in the PI’s office (Dr Tim Betts).  This office only be accessed by authorised personnel via 
a door-code and it is also located in the John Radcliffe Hospital, Level 2 Blue Outpatients.  
The name and any other identifying detail will NOT be included in any trial data electronic file. 
The LINQ™ and the Confirm Rx™ only transmit recordings to their company’s servers (Carelink™, for 
Medtronic; Merlin.net™, for Abbott) via their respective smartphone app.  ICM recordings can only be 
accessed on these servers by using the clinician web portal. This is the routine clinical practice in OUH for 
devices which are one remote monitoring (patients don’t have to physically attend hospital for a device 
interrogation). Smartphone apps from Medtronic and Abbott are already used OUH to transmit 
information from the devices rather than using home-based monitors. The assigned trial specific ID 
number will be used to register the device in the Carelink (for Medtronic devices) and Merlin.net (for 
Abbott devices); thus, no identifiable patient information will be in the servers. Access to these servers is 
via the clinician web portal is password protected.  
Transmission reports will be downloaded from the Medtronic™ and Abbott™ servers and stored in 
password protect excel spreadsheet that will only be used in OUH trust computers.  
Personal data will not be kept more than 3 months following the end of the study. Study data will be 
kept for a minimum of five years.  
 
 
13 QUALITY ASSURANCE PROCEDURES 
The study may be monitored, or audited in accordance with the current approved protocol, GCP, 
relevant regulations and standard operating procedures.  
13.1 
Risk assessment  
Not applicable 
13.2 
Study monitoring  
The study will be monitored via the study amendments and progress reports. If any issues arise the study 
may be monitored, or audited in accordance with the current approved protocol, ICH GCP, relevant 
regulation and standard operating procedures. 
 

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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Not applicable: 
13.3 
Study Committees  
 
This is a small, single-centre study using commonly available devices with minimal patient risk, no 
oversight committees are required.  
14 PROTOCOL DEVIATIONS  
A study related deviation is a departure from the ethically approved study protocol or other study 
document or process (e.g. consent process or administration of study intervention) or from Good Clinical 
Practice (GCP) or any applicable regulatory requirements. Any deviations from the protocol will be 
documented in a protocol deviation form and filed in the study master file. 
15 SERIOUS BREACHES 
A “serious breach” is a breach of the protocol or of the conditions or principles of Good Clinical Practice 
which is likely to affect to a significant degree – 
 (a) the safety or physical or mental integrity of the trial subjects; or 
(b) the scientific value of the research. 
In the event that a serious breach is suspected the Sponsor must be contacted within 1 working day. In 
collaboration with the C.I., the serious breach will be reviewed by the Sponsor and, if appropriate, the 
Sponsor will report it to the approving REC committee and the relevant NHS host organisation within 
seven calendar days.  
16 ETHICAL AND REGULATORY CONSIDERATIONS 
16.1 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of the 
Declaration of Helsinki. 
16.2 
Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in accordance with relevant regulations and with 
Good Clinical Practice. 
16.3 
Approvals 
Following Sponsor approval, the protocol, informed consent form, participant information sheet will be 
submitted to an appropriate Research Ethics Committee (REC), and HRA (where required) and host 
institutions for written approval. 

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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The Investigator will submit and, where necessary, obtain approval from the above parties for all 
substantial amendments to the original approved documents. 
16.4 
Reporting 
The CI shall submit once a year throughout the study, or on request, an Annual Progress report to the 
REC Committee, HRA (where required) host organisation, Sponsor and funder (where required). In 
addition, an End of Study notification and final report will be submitted to the same parties. 
 
16.5 
Other ethical issues 
In the event of a clinically relevant arrhythmia being detected by the ICM but not by the pacemaker, the 
research team will take steps to quickly inform the subject’s clinical team so that if required, it can be 
promptly acted upon’ 
 
16.6 
Participant Confidentiality 
The study will comply with the General Data Protection Regulation (GDPR) and Data Protection Act 2018, 
which require data to be de-identified as soon as it is practical to do so. The processing of the personal 
data of participants will be minimised by making use of a unique participant study number only on all 
study documents and any electronic database, with the exception of the CRF, where participant initials 
may be added.  All documents will be stored securely and only accessible by study staff and authorised 
personnel. The study staff will safeguard the privacy of participants’ personal data. 
No identifiable details will be published. 
16.7 
Expenses and Benefits 
Reasonable travel expenses for any visits additional to normal care will be reimbursed on production of 
receipts, or a mileage allowance provided as appropriate. 
17 FINANCE AND INSURANCE 
17.1 
Funding 
This trial will be partially supported by a grant from Abbott Medical Grant,  Medtronic Grant or 
consumables and Rhythm Management Research Hub.  
         17.2             Insurance 
NHS bodies are legally liable for the negligent acts and omissions of their employees. If you are harmed 
whilst taking part in a clinical research study as a result of negligence on the part of a member of the 
study team this liability cover would apply. 

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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Non-negligent harm is not covered by the NHS indemnity scheme. The Oxford University Hospitals NHS 
Foundation Trust, therefore, cannot agree in advance to pay compensation in these circumstances. 
In exceptional circumstances an ex-gratia payment may be offered. 
17.3 
Contractual arrangements  
Appropriate contractual arrangements will be put in place with all third parties.  
18 PUBLICATION POLICY 
The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and 
any other publications arising from the study.   
Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be 
acknowledged. 
19 DEVELOPMENT OF A NEW PRODUCT/ PROCESS OR THE GENERATION OF INTELLECTUAL 
PROPERTY  
Ownership of IP generated by employees of the OUH vests in OUH.  The protection and exploitation of 
any new IP is managed by the IP and Research Contracts Team at OUH unless it is generated in 
collaboration with Oxford University in which case this is led by the University’s technology transfer 
office, Oxford University Innovations. 
20 ARCHIVING 
All documents will be stored securely in Clinical Fellows Research Office in the John Radcliffe Hospitals   
which requires a code to gain entrance to the office.  The documents will only be accessible by study 
staff and authorised personnel.  
The study staff will safeguard the privacy of participants’ personal data. 
 
21 REFERENCES 
1. 
January, C.T., et al., 2014 AHA/ACC/HRS guideline for the management of patients with atrial 
fibrillation: a report of the American College of Cardiology/American Heart Association Task 
Force on Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol, 2014. 64(21): p. e1-
76. 
2. 
Kirchhof, P., et al., 2016 ESC Guidelines for the management of atrial fibrillation developed in 
collaboration with EACTS. Eur Heart J, 2016. 37(38): p. 2893-2962. 
3. 
Kannel, W.B., et al., Prevalence, incidence, prognosis, and predisposing conditions for atrial 
fibrillation: population-based estimates 11Reprints are not available. The American Journal of 
Cardiology, 1998. 82(7, Supplement 1): p. 2N-9N. 

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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4. 
Lin, H.-J., et al., Stroke severity in atrial fibrillation: the Framingham Study. Stroke, 1996. 27(10): 
p. 1760-1764. 
5. 
Quirino, G., et al., Diagnosis of paroxysmal atrial fibrillation in patients with implanted 
pacemakers: relationship to symptoms and other variables. Pacing Clin Electrophysiol, 2009. 
32(1): p. 91-8. 
6. 
Capucci, A., et al., Monitored atrial fibrillation duration predicts arterial embolic events in 
patients suffering from bradycardia and atrial fibrillation implanted with antitachycardia 
pacemakers. J Am Coll Cardiol, 2005. 46(10): p. 1913-20. 
7. 
Sarkar, S., et al., Burden of atrial fibrillation and poor rate control detected by continuous 
monitoring and the risk for heart failure hospitalization. Am Heart J, 2012. 164(4): p. 616-24. 
8. 
Brignole, M., et al., 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart 
J, 2018. 39(21): p. 1883-1948. 
9. 
Hanke, T., et al., Twenty-Four–Hour Holter Monitor Follow-Up Does Not Provide Accurate Heart 
Rhythm Status After Surgical Atrial Fibrillation Ablation Therapy. Circulation, 2009. 
120(11_suppl_1): p. S177-S184. 
10. 
Sanna, T., et al., Cryptogenic Stroke and Underlying Atrial Fibrillation. New England Journal of 
Medicine, 2014. 370(26): p. 2478-2486. 
11. 
Podd, S.J., et al., Are implantable cardiac monitors the 'gold standard' for atrial fibrillation 
detection? A prospective randomized trial comparing atrial fibrillation monitoring using 
implantable cardiac monitors and DDDRP permanent pacemakers in post atrial fibrillation 
ablation patients. Europace, 2016. 18(7): p. 1000-5. 
12. 
Healey, J.S., et al., Subclinical atrial fibrillation and the risk of stroke. N Engl J Med, 2012. 366(2): 
p. 120-9. 
13. 
de Voogt, W.G., et al., Verification of pacemaker automatic mode switching for the detection of 
atrial fibrillation and atrial tachycardia with Holter recording. Europace, 2006. 8(11): p. 950-61. 
 
 
 

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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22 APPENDIX A:  STUDY FLOW CHART 
 
 
 
 
 
Screening & recruitment 
Eligibility, Baseline 
Assessment  
Block Randomisation 
15 Confirm  
Rx ICM 
15 LINQ 
ICM 
ICM Implant 
Device Telephone Clinic Review (1 month) 
ICM explant (optional) 
Device Clinic Review   (6 months) 
Monthly Remote Transmissions (2 -5 months) 
VISIT 0 
VISIT 1 
VISIT 2 

 
 
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ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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23 APPENDIX B:  SCHEDULE OF STUDY PROCEDURES 
 
Procedures 
Number of visits: 3 
Assessment 
Visit 1 
(Telephone 
Clinic) 
 
Final visit 
Day 0 
 Day 0 
Day 0 
4-6 weeks 
2-5 
months 
6 Months 
Screening 
Baseline 
Implant 
 
Monthly 
Remote 
Downloads 
Device 
interrogation  
ICM explant 
Informed consent 
x 
 
 
 
 
 
Demographics 
x 
 
 
 
 
 
Medical history 
x 
 
 
x 
 
 
Physical 
examination  
x 
 
 
 
 
 
Medications 
 
x 
 
x 
 
 
Eligibility 
assessment 
x 
 
 
 
 
 
Implant indication  
 
x 
 
 
 
 
Randomisation 
 
x 
 
 
 
 
ICM Implant 
 
 
x 
 
 
 
Device 
interrogation 
and 
programming 
 
 
 
x 
x 
x 
ICM Explant 
 
 
 
 
 
x 
Adverse 
event 
assessments  
 
 
 
 
 
x 
 
 
 

 
 
Trial Protocol                                                                                                                                  Version 1.21 /Date: 0326/087/20231  
ID-AF Study                                                                                                                                       IRAS Project number: 268739 
Chief Investigator: Prof Tim Betts                                                                                                         REC Ref: 21/LO/0508<  
 
 
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24 APPENDIX C:  AMENDMENT HISTORY 
 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes made 
 
 
 
 
 
 
List details of all protocol amendments here whenever a new version of the protocol is produced.  This is 
not necessary prior to initial REC / HRA submission. 
Protocol amendments must be submitted to the Sponsor for approval prior to submission to the REC 
committee and HRA (where required).