Randomised Controlled Trial of the Use of a Smart Phone Based Event Recorder Versus Standard Care for Patients Presenting to the Emergency Department With Palpitations and Pre-syncope
Phase: NA
Conditions: Presyncope, Arrhythmias, Cardiac, Tachycardia, Supraventricular, Atrial Fibrillation
Sponsor: NHS Lothian

The IPED study: Protocol version 3.0 
 
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Randomised controlled trial of the use of a smart 
phone based event recorder versus standard care for 
patients presenting to the Emergency Department with 
palpitations and pre-syncope 
 
The IPED (Investigation of Palpitations in the ED) study 
 
 
 
Protocol version 3.0 
 
Date: 09/10/2016 
 
 
 

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IRAS Project ID: 196616 
 
 
 
 
 
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Study Protocol 
 
Randomised controlled trial of the use of a smart phone based event recorder versus 
standard care for patients presenting to the Emergency Department with palpitations 
and pre-syncope 
The IPED study  
Sponsor 
Lothian NHS Health Board 
Sponsor contact address 
NHS Lothian R&D 
ACCORD 
The Queen’s Medical Research Institute 
47 Little France Crescent 
Edinburgh 
EH16 4TJ 
Funder 
Chest, Heart and Stroke Scotland 
Funding Reference Number 
R15/A164 
Chief Investigator 
Dr Matthew Reed  
REC Number 
IRAS project ID 196616; REC Number awaited 
ClinicalTrials.gov identifier 
NCT02783898 
Version Number and Date 
Version: 3.0    Date: 24/08/2016  
 
COORDINATING CENTRE 
 
Chief Investigator  
Dr Matthew Reed * 
Consultant in Emergency Medicine.  
Emergency Medicine Research Group 
Edinburgh (EMERGE),  
Royal Infirmary of Edinburgh,  
51 Little France Crescent,  
Edinburgh, EH16 4SA, UK. 
Tel: 0131 242 3863  
Fax: 0131 242 1339  
Email: matthew.reed@nhslothian.scot.nhs.uk 
Sponsor Representative 
Susan Shepherd  
Head of Research Governance 
NHS Lothian Research & Development Office 
Queen's Medical Research Institute 
47 Little France Crescent 
Edinburgh 
EH16 4TJ  
Tel: 0131 242 3359 
Email: 
Susan.Shepherd@nhslothian.scot.nhs.uk 
Research Nurse Co-ordinator 
Rachel O’Brien 
Emergency Medicine Research Group 
Edinburgh (EMERGE),  
Department of Emergency Medicine,  
Royal Infirmary of Edinburgh,  
51 Little France Crescent,  
Edinburgh, EH16 4SA, UK. 
 
Tel: 0131 242 3863  
Email: rachel.o’brien@nhslothian.scot.nhs.uk 
 
Study Statistician 
Sharon Tuck * 
Statistician 
Wellcome Trust Clinical Research Facility  
Western General Hospital 
Crewe Road South 
Edinburgh 
EH4 2XU 
 
Tel: 0131 537 3352 
Email: Sharon.Tuck@ed.ac.uk 
 

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Co-Investigator 
Dr Neil Grubb 
Consultant in Cardiology and Cardiac 
Electrophysiology, 
Department of Cardiology, 
Royal Infirmary of Edinburgh,  
51 Little France Crescent,  
Edinburgh,  
EH16 4SA, UK 
 
Email: neil.grubb@nhslothian.scot.nhs.uk 
Co-Investigator 
Dr Chris Lang 
Consultant in Cardiology and Cardiac 
Electrophysiology, 
Department of Cardiology, 
Royal Infirmary of Edinburgh,  
51 Little France Crescent,  
Edinburgh,  
EH16 4SA, UK 
 
Email: chris.lang@nhslothian.scot.nhs.uk 
 
 
 
* Protocol authors

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CONTENTS 
 
1 
INTRODUCTION ............................................................................................................... 9 
1.1 
BACKGROUND ........................................................................................................ 9 
1.2 
RATIONALE FOR STUDY ........................................................................................ 9 
2 
STUDY OBJECTIVES ..................................................................................................... 10 
2.1 
OBJECTIVES ......................................................................................................... 10 
2.1.1 
Primary Objective .............................................................................................. 10 
2.1.2 
Secondary Objectives ....................................................................................... 10 
2.2.3 
Primary Endpoint .............................................................................................. 10 
2.2.4 
Secondary Endpoints ........................................................................................ 10 
3 
STUDY DESIGN .............................................................................................................. 10 
4 
STUDY POPULATION .................................................................................................... 10 
4.1 
NUMBER OF PARTICIPANTS ............................................................................... 10 
4.2 
INCLUSION CRITERIA ........................................................................................... 11 
4.3 
EXCLUSION CRITERIA ......................................................................................... 11 
4.4 
CO-ENROLMENT ................................................................................................... 11 
5 
PARTICIPANT SELECTION AND ENROLMENT .......................................................... 11 
5.1 
IDENTIFYING PARTICIPANTS .............................................................................. 11 
5.2 
CONSENTING PARTICIPANTS ............................................................................. 11 
5.3 
SCREENING FOR ELIGIBILITY ............................................................................. 12 
5.4 
INELIGIBLE AND NON-RECRUITED PARTICIPANTS ......................................... 12 
5.5 
RANDOMISATION .................................................................................................. 12 
5.5.1 
Randomisation Procedures ............................................................................... 12 
5.5.2 
Treatment Allocation ......................................................................................... 12 
5.5.3 
Withdrawal of Study Participants ...................................................................... 12 
6 
STUDY ASSESSMENTS ................................................................................................ 12 
6.1 
SAFETY ASSESSMENTS ...................................................................................... 12 
6.2 
STUDY ASSESSMENTS ........................................................................................ 13 
7 
DATA COLLECTION ...................................................................................................... 14 
8 
STATISTICS AND DATA ANALYSIS ............................................................................. 14 
8.1 
SAMPLE SIZE CALCULATION .............................................................................. 14 
8.2 
PROPOSED ANALYSES ....................................................................................... 14 
9 
ADVERSE EVENTS ...................................................................................................... 14 
10 
PREGNANCY ................................................................................................................ 14 
11 
TRIAL MANAGEMENT AND OVERSIGHT ARRANGEMENTS .................................. 15 
11.1 
TRIAL MANAGEMENT GROUP ........................................................................... 15 
11.2 
TRIAL STEERING COMMITTEE .......................................................................... 15 
11.3 
DATA MONITORING COMMITTEE ..................................................................... 15 
11.4 
INSPECTION OF RECORDS ............................................................................... 15 
11.5 
RISK ASSESSMENT ............................................................................................ 15 
11.6 
STUDY MONITORING AND AUDIT ..................................................................... 15 
12 
GOOD CLINICAL PRACTICE ....................................................................................... 15 

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12.1 
ETHICAL CONDUCT ............................................................................................ 15 
12.2 
INVESTIGATOR RESPONSIBILITIES ................................................................. 15 
12.2.1 Informed Consent ............................................................................................. 15 
12.2.2 Study Site Staff ................................................................................................. 16 
12.2.3 Data Recording ................................................................................................. 16 
12.2.4 GCP Training .................................................................................................... 16 
12.2.5 Confidentiality ................................................................................................... 16 
12.2.6 Data Protection ................................................................................................. 16 
13 
STUDY CONDUCT RESPONSIBILITIES ..................................................................... 17 
13.1 
PROTOCOL AMENDMENTS ............................................................................... 17 
13.2 
PROTOCOL VIOLATIONS AND DEVIATIONS .................................................... 17 
13.3 
SERIOUS BREACH REQUIREMENTS ................................................................ 18 
13.4 
STUDY RECORD RETENTION ........................................................................... 18 
13.5 
END OF STUDY ................................................................................................... 18 
13.6 
INSURANCE AND INDEMNITY ........................................................................... 18 
14 
REPORTING, PUBLICATIONS AND NOTIFICATION OF RESULTS ......................... 19 
14.1 
AUTHORSHIP POLICY ........................................................................................ 19 
14.2 
PUBLICATION ...................................................................................................... 19 
14.3 
PEER REVIEW ..................................................................................................... 19 
15 
REFERENCES .............................................................................................................. 19 
 

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PROTOCOL APPROVAL 
The IPED study 
Signatures 
 
 
 
 
Dr Matthew Reed 
 
 
 
Chief Investigator 
Signature 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sharon Tuck 
 
 
 
Study Statistician 
Signature 
 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Susan Shepherd 
 
 
 
Sponsor(s) Representative 
Signature 
 
Date 

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LIST OF ABBREVIATIONS 
 
ACCORD 
Academic and Clinical Central Office for Research & Development - 
Joint office for University of Edinburgh and NHS Lothian 
AE 
Adverse Event 
AF 
Atrial Fibrillation 
AMU 
Acute Medical Unit (or equivalent) 
AR 
Adverse Reaction 
CHSS 
Chest, Heart & Stroke, Scotland 
CRF 
Case Report Form 
CV 
Curriculum Vitae 
GCP 
Good Clinical Practice 
ECG 
Electrocardiogram 
ED 
Emergency Department 
EMERGE 
Emergency Medicine Research Group of Edinburgh 
EPR 
Electronic Patient Record 
ICH 
International Conference on Harmonisation 
IMP 
Investigational Medicinal Product 
ISF 
Investigator Site File 
MACE 
Major Adverse Cardiac Event 
NYHA 
New York Heart Association 
QA 
Quality Assurance 
R&D 
Research and Development 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event 
SAR 
Serious Adverse Reaction 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
SVT 
Supraventricular Tachycardia 
TMF 
Trial Master File 
UAR 
Unexpected Adverse Reaction 
VF 
Ventricular Fibrillation  
VT 
Ventricular Tachycardia 

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SUMMARY 
 
Palpitations (noticeable pounding, fluttering or irregular heart beat) and pre-syncope (near 
blackout) are common ED problems sometimes due to an abnormal cardiac rhythm. This is 
difficult to diagnose as examination and electrocardiogram (ECG) are commonly normal and 
symptoms have usually resolved by the time the patient arrives in the ED. Diagnosing an 
abnormal heart rhythm as the cause of symptoms rests on capturing it on an ECG and 
patients are usually discharged with advice to return to the ED again for a 12-lead ECG 
should symptoms recur. We believe a smart phone based event recorder will allow better and 
earlier diagnosis in patients with a compatible smart phone or tablet, and revolutionise ED 
care in this area. 
 

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1 
INTRODUCTION 
1.1 
BACKGROUND 
Palpitations (the noticeable pounding, fluttering or irregular beating of the heart) and pre-
syncope (the sudden onset of a sense of impending loss of consciousness) are together 
responsible for 1.0% of ED visits (300,000 annual ED attendances in the UK) [1,2]. They are 
less likely to be due to serious arrhythmia than syncope (sudden onset of brief loss of 
consciousness) and are more likely due to conditions such as atrial fibrillation (AF) and 
supraventricular tachycardia (SVT). Diagnosis of the underlying rhythm is difficult as many 
patients are fully recovered on ED arrival and examination and presenting ECG are 
commonly normal. Many episodes are due to benign causes such as anxiety or frequent 
ectopics (extra or skipped heart beats). 
 
The only way to establish the underlying heart rhythm is to capture an ECG during symptoms. 
Many patients go for years without diagnosis due to the difficulty in capturing the underlying 
heart rhythm. 12-lead ECG and conventional ambulatory devices are of limited use due to the 
infrequency of symptoms in many patients. Most are discharged from the ED and asked to 
represent or phone 999 should they get further symptoms in the hope of capturing the 
episode on a standard 12-lead ECG. 
 
Recent technology advances have led to several novel ECG monitoring devices appearing on 
the market. The Emergency Medicine Research Group, Edinburgh (EMERGE) with CHSS 
support, is currently evaluating a continuous ambulatory ECG monitor (ZIO®XT Patch) for 
use in syncope patients. This is a pilot study aiming to recruit 100 participants by December 
2016. Devices that continuously monitor are vital to detect underlying cardiac rhythm in 
patients with syncope as the patient has lost consciousness and is therefore not able to use 
devices that require the patient to trigger the ECG recording (event recorders).  
 
The pocket sized AliveCor Heart Monitor and AliveECG phone/tablet app is a monitoring 
device that requires the patient to trigger the ECG recording. It is available for both Apple and 
Android mobile and tablet operating systems and was CE marked in January 2015 [3]. With 
minimal training, two fingers from each hand are placed on the monitor (which can be 
connected to the back of a smart phone) for 30 seconds to take an ECG recording, which is 
transmitted wirelessly to the app, analysed and synchronised to an encrypted server. The 
patient can then alert their healthcare professional to allow their ECG to be viewed securely 
[3].  
 
The Arrhythmia Alliance [3] distributed AliveCor Heart Monitors to 1500 people of all ages. 
Only one returned their monitor because it caused them to worry and check their heart rate 
too often. 26% of recordings showed a previously undetected arrhythmia and 5% were 
advised to see their doctor urgently. They reported the AliveCor Monitor was ‘easy for people 
of all ages to use, and could save money for the NHS when compared with the cost of 
standard NHS ECG recordings.’ Older people were also noted to be regular users of mobile 
technology and gave positive feedback about the system.  
1.2 
RATIONALE FOR STUDY 
There have been few studies investigating the use of smart phone based event recorders [4-
7], and none in an acute or ED population, where large numbers of patients present. We 
believe this smart phone event recorder will allow ED patients who have presented with 
palpitations or pre-syncope to record their ECG tracing if they have a further episode 
increasing the rate of underlying rhythm diagnosis. 

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2 
STUDY OBJECTIVES 
2.1 
OBJECTIVES 
2.1.1 Primary Objective 
To compare the symptomatic rhythm detection rate at 90 days of a smart phone based event 
recorder (AliveCor Monitor) compared to standard care for participants presenting to the ED 
with palpitations and pre-syncope with no obvious cause in the ED. 
2.1.2 Secondary Objectives 
1. To investigate the symptomatic rhythm detection rate for cardiac arrhythmia detection 
at 90 days of a smart phone based event recorder compared to standard care for 
participants presenting to the ED with palpitations and pre-syncope 
2. To compare the time to detection of symptomatic rhythm versus standard care 
3. To compare the time to detection of cardiac arrhythmia versus standard care 
4. To compare the number of participants treated or (planned for treatment) for cardiac 
arrhythmia versus standard care 
5. To investigate participant satisfaction and monitor compliance 
6. To compare the cost of symptomatic rhythm detection at 90 days of a smart phone 
based event recorder compared to standard care for participants presenting to the ED 
with palpitations and pre-syncope 
7. To compare serious outcomes at 90 days in participants using a smart phone based 
event recorder compared to standard care 
2.1.3 Primary Endpoint 
Symptomatic rhythm detection rate of a smart phone based event recorder for symptomatic 
rhythm detection at 90 days versus standard care. 
2.1.4 Secondary Endpoints 
1. Symptomatic rhythm detection rate of a smart phone based event recorder for cardiac 
arrhythmia detection at 90 days versus standard care 
2. Time to detection of symptomatic rhythm using a smart phone based event recorder 
versus standard care 
3. Time to detection of cardiac arrhythmia rhythm using a smart phone based event 
recorder versus standard care 
4. Number of participants treated or (planned for treatment) for cardiac arrhythmia in 
participants using a smart phone based event recorder versus standard care 
5. Participant satisfaction and monitor compliance 
6. Cost effectiveness analysis 
7. Serious outcomes at 90 days: all cause death and major adverse cardiac events 
[MACE] (myocardial infarction, life-threatening arrhythmia, insertion of a pacemaker 
or internal cardiac defibrillator, insertion of pacing wire).  
3 
STUDY DESIGN 
This is a multi-centre hospital ED / AMU open label, randomised controlled trial of participants 
aged 16 years or over presenting with an episode of palpitations or pre-syncope and whose 
underlying ECG rhythm during these episodes remains undiagnosed after ED assessment. 
Participants will be followed-up at 90 days using hospital records, contacting participant GP 
and also by contacting the participants themselves.  This study is expected to take around 18 
months to complete from first participant recruited to last participants’ 90-day follow-up.  

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4 
STUDY POPULATION 
4.1 
NUMBER OF PARTICIPANTS 
242 consecutive participants aged 16 years or over presenting with an episode of palpitations 
or pre-syncope and whose underlying ECG rhythm during these episodes remains 
undiagnosed after ED assessment shall be recruited into the study. Recruitment will last 
around 15 months.  
4.2 
INCLUSION CRITERIA 
1. Participant aged 16 years or over 
2. Participant presenting with an episode of palpitations or pre-syncope with no obvious 
cause 
3. Participant’s underlying ECG rhythm during these episodes remains undiagnosed 
after clinical assessment. 
4.3 
EXCLUSION CRITERIA 
1. Prior diagnostic ECG  
2. Palpitations or pre-syncope present during an admission ECG 
3. Frequent episodes (i.e. at least once a day) 
4. Participants under 16 years of age 
5. Previous participation in the study 
6. Alcohol / illicit drugs / seizure / stroke / transient ischemic attack / head trauma / 
hypoglycemia as presumptive cause 
7. Inability or unwilling to give informed consent. 
8. Participants with recent (i.e. within 3 months) myocardial infarction, severe heart 
failure (NYHA class 4) or unstable angina 
9. Participants unwilling or unable to use the AliveCor Heart Monitor and AliveECG app 
10. Participants without a compatible smart phone or tablet  
11. Participants with cardiac pacemakers or other implanted electronic devices 
12. No telephone number for follow-up 
13. Participant in custody 
4.4 
CO-ENROLMENT 
Co-enrolment will be permitted with non-interventional studies that involve data collection 
only.  Co-enrolment with another interventional study may be allowed provided this is not 
expected to place an undue burden upon participants and their families, and will not 
compromise the primary end-point of either study.  Consideration will also be given to the 
burden on the participant. Co-enrolment will only be permitted with agreement of the Chief 
Investigators of both studies. 
5 
PARTICIPANT SELECTION AND ENROLMENT 
5.1 
IDENTIFYING PARTICIPANTS 
 
The research nurses, where it is locally agreed that they are part of the clinical care team, will 
identify patients using triage information and clinical or electronic records in the ED or the 
AMU. In this case, it is anticipated they would identify patients and make the first approach. 
Any member of the clinical team who has received general and trial specific training and is on 
the delegation log may also identify patients in this way.  
 
If research nurses are not considered to be part of the direct care team locally, activities 
carried out prior to consent (including identification) will be carried out by a member of the 
direct care team. 
 
Where research nurses are not considered to be part of the care team, the research nurse 
should ask a member of the direct care team to identify suitable patients and ask permission 
from the patient to be approached by the research nurse to discuss participation. 

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5.2 
CONSENTING PARTICIPANTS 
If the potentially eligible participant fulfils the study eligibility criteria, a member of the study 
research team (or direct care clinician if suitably trained) will take written consent.  
 
The participant is assessed by the direct care team to establish if he/she is competent and 
has capacity to consent. This assessment will be documented in the medical notes i.e. this 
participant is eligible and capable of providing written informed consent. Participants lacking 
capacity who are unable to provide consent will not be approached to take part in the study. 
 
The participant (and, if present and appropriate, their accompanying relative) will be given a 
Participant Information Sheet, which will explain the aims of the study and the potential risks 
and benefits of the study procedures/tests. 
 
The participant will be given enough time to consider the study and ask questions regarding 
their participation in the study. For some participants this could be as much as an hour but for 
others may only be 10-15 minutes. If the participant agrees, informed consent will be 
confirmed with a signature on the study consent form. The original consent form will be filed in 
the Investigator Site File (ISF), the participant will receive a copy of this document and a copy 
will be filed in the participant’s medical notes. 
 
Potential, eligible participants who are able to express their consent and able to complete the 
consent form will be asked to provide written consent. The recruiting direct care clinician or 
member of the research team will do this. A witness will sign to confirm that all the study 
information was given and the participant consented to taking part in the study for participants 
who are able to express their consent but unable to sign. 
5.3 
SCREENING FOR ELIGIBILITY 
There is a requirement to ensure Good Clinical Practice for published studies and to include a 
Consort diagram [8] of numbers of participants with the study condition during the study 
period who for one reason or another were not enrolled in the study. In order to determine the 
number of eligible but not recruited participants during the study period, the ED patient record 
of all potentially eligible participants will be interrogated by a member of the study research 
team (if part of the participant’s direct care team). 
 
An anonymised log will be kept for patients who were screened for the study and those who 
were subsequently found to be ineligible or who were not recruited. 
5.4 
INELIGIBLE AND NON-RECRUITED PARTICIPANTS 
Non-recruited but potentially eligible participants will be identified by a daily search of all acute 
patient admissions records to assess for potential selection/recruitment bias. Ineligible 
patients will not be recorded. 
 
 
5.5 
RANDOMISATION 
5.5.1 Randomisation Procedures 
Participants will be equally distributed between the two study arms with 121 participants in 
each arm. Randomisation will be by block randomisation. Randomisation codes will be 
generated and blinded envelopes will be prepared and labelled in accordance with the 
randomisation list for each participating site. Randomisation codes will be held by each 
recruiting ED in an area of the ED accessible to the research team. Participants eligible for 
inclusion should be randomised by taking the next lowest consecutively numbered envelope.  
5.5.2 Treatment Allocation 
Participants will be allocated either to (a) STUDY arm; standard care plus the use of a smart 
phone based event recorder or (b) CONTROL arm; standard care, depending on the group 
allocated in the study envelope. 
5.5.3 Withdrawal of Study Participants 

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If a participant wishes to withdraw from the study they will be removed. We will establish 
whether they consent to allow the use of all data collected up to the date of removal. They will 
not be replaced. 
6 
STUDY ASSESSMENTS 
6.1 
SAFETY ASSESSMENTS 
This study has been risk assessed by the Medical Physics and Infection Control teams at the 
Royal Infirmary of Edinburgh. An Infection Control agreed SOP for cleaning the AliveCor 
Heart Monitor Device prior to re-use is included in the study paperwork. 
6.2 
STUDY ASSESSMENTS 
Potentially eligible ED and AMU participants will be identified and assessed for study 
inclusion by the attending clinician. Written consent will be taken and participants will have a 
Case Report Form (CRF) completed and a 12-lead ECG taken if not already performed by the 
clinical team.  
All STUDY arm participants will be given an AliveCor Heart Monitor and trained in the use of 
the device and app in the ED or AMU by the research team.  
CONTROL arm participants will receive no other intervention.  
Participants in both groups will be admitted, referred or discharged by the treating clinician 
according to current local hospital protocols.  
Participants in both groups will be followed up at 90 days through hospital record systems 
(paper or electronic depending on local policy), GP records and by telephone by the local 
study team. Participants will also be asked to complete a standardised written questionnaire 
and will receive a follow-up telephone call from the local study team enquiring about 
symptoms and contact with medical services. Participants will also be asked about 
satisfaction and compliance with the heart monitor. 
 
Participants allocated to the Study arm may be contacted by telephone by the local research 
team shortly after randomisation in the event of them requiring further training or setting up of 
the device. For example, this may be necessary if a participant does not have their app store 
password with them in the ED or AMU. If a local electronic patient record system is available, 
then a research alert will be placed on this stating that the participant has consented to be 
part of the IPED study.  
 
If a participant allocated to the Study arm, gets an episode of palpitations or pre-syncope and 
is able to record an AliveCor Heart Monitor ECG during the episode, the participant will email 
the ECG recorded by the AliveCor app directly to the co-ordinating Edinburgh research team 
at a convenient time to the participant and to a secure nhs.net email address. This email 
includes a pdf attachment of the ECG tracing along with the participant’s AliveCor app login 
(which will be their IPED study number -  no identifiable participant data will leave the local 
site, only the participants email address and IPED study number will appear), time and date of 
recording, and ECG recording. AliveCor collects non-sensitive usage data through a third 
party service called Mixpanel. Participant will not be asked to send their ECGs to AliveCor 
directly for analysis. The AliveCor app rhythm analysis algorithm will automatically report any 
ECG recorded by the AliveCor app as Normal, Atrial Fibrillation or Unclassified. 
 
The co-ordinating Edinburgh research team will review the ECG and will contact the local 
study team to arrange follow-up if required. If specialist follow-up of the ECG tracing is not 
required then the local study team will write to the participant informing them of this (Patient 
ECG follow-up letter normal v2.0 24082016 and Patient ECG follow-up letter abnormal v2.0 
24082016) and asking them to arrange follow up with their general practitioner who will be 
contacted with the report (GP Follow up Letter v2.0 24082016). The participant and GP will 
not be contacted further should participants record other similar ECGs that similarly do not 
require specialist follow-up.  
 
If the participant records a serious significant arrhythmia i.e. 

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• 
ventricular fibrillation (VF) 
• 
ventricular tachycardia (VT) (it will be assumed that this is symptomatic given the 
participant has chosen to record an ECG during the episode) 
• 
complete or 3rd degree heart block 
• 
second degree heart block type II (it will be assumed that this is symptomatic given 
the participant has chosen to record an ECG during the episode) 
• 
pause >6 seconds 
• 
symptomatic bradycardia <40 beats per minute 
 
during the study period, the local study team will alert the participant immediately by 
telephone, and refer them urgently to their local Emergency Department or cardiac 
electrophysiology service (as per local protocol).  
 
Participants will be asked to log any symptoms along with the time and date, type of symptom 
and whether they were able to record an ECG during the symptoms, in a participant symptom 
diary. They will return this diary to the local research team along with the Participant 
satisfaction and compliance questionnaire, and smart phone based event recorder at the end 
of the 90 days in a pre-paid stamped, addressed envelope. Participants will be phoned at 90 
days by the local study team to remind them to complete the Participant satisfaction and 
compliance questionnaire and to return this to the local study team with the symptom diary 
and smart phone based event recorder. The compliance questionnaire is designed to capture 
whether participants had the device with them and were able to record a heart tracing during 
symptoms. This will be entered onto the study database by the local study team. 
7 
DATA COLLECTION 
Participants will have a CRF completed during index hospitalisation, comprising demographic, 
historical and examination characteristics. An ECG will also be taken and stored. Participant 
contact details will also be confirmed including a telephone number and email address. Once 
a participant has been randomised, the baseline CRF will be sent to the local study team 
office. The information on the CRF will be entered into a specially designed password 
protected online accessed secure database (REDCAP; http://www.project-redcap.org) the 
server of which is held within the University of Edinburgh. No participant identifiable 
information will leave the recruiting NHS hospital or be entered onto REDCAP. Participants 
will be identified on REDCAP by study number alone. 
8 
STATISTICS AND DATA ANALYSIS 
8.1 
SAMPLE SIZE CALCULATION 
Using a symptomatic rhythm detection rate at 90 days of 25% [3] versus standard care (10%) 
we estimate 110 participants in each group would have 80% power to determine a 15% 
improvement in symptomatic rhythm detection. We will recruit an extra 10% in each arm to 
allow for drop out (i.e. 121 participants in each arm). Our ED sees around 500 eligible 
participants a year. Assuming a 50% recruitment rate we estimate we will need to recruit for 
15 months. 
8.2 
PROPOSED ANALYSES 
Descriptive analysis of participant characteristics shall be presented split by study arm.  
Baseline to 90 day change in diagnostic yield between the two study arms will be analysed 
using two sample t-tests or non-parametric equivalent as appropriate.  Log-rank tests and 
Kaplan-Meier curves shall be used to examine if the smartphone recorder has an effect on 
detecting symptomatic rhythm and cardiac arrhythmia separately up to 90 days versus 
standard care. Categorical variables will be compared using a χ2 test (and χ2 test for trend if 
appropriate). All participants will be analysed on an intention to treat basis.  

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9 
ADVERSE EVENTS 
A secondary endpoint for the study is serious outcomes at 90 days: all cause death and major 
adverse cardiac events [MACE] (myocardial infarction, life-threatening arrhythmia, insertion of 
a pacemaker or internal cardiac defibrillator, insertion of pacing wire). This data will therefore 
be routinely collected as part of the study and not recorded as an Adverse Event (AE). 
Hospital admission will also not be recorded as an AE. The only AEs recorded will be those 
directly related to the use of the smart phone based event recorder and application.  
10 
PREGNANCY 
Pregnancy is not an exclusion criteria for the IPED study. 
11 
TRIAL MANAGEMENT AND OVERSIGHT 
ARRANGEMENTS 
11.1 TRIAL MANAGEMENT GROUP 
The study will be coordinated by a Project Management Group consisting of the Chief 
Investigator, Co-Investigators, Statistician and Research Team.  
EMERGE will oversee the study and will be accountable to the Chief Investigator.  EMERGE 
will be responsible for checking the electronic CRFs for completeness, plausibility and 
consistency.  The Chief Investigator and EMERGE will resolve any queries.  
A Delegation Log will be prepared detailing the responsibilities of each member of staff 
working on the study.   
11.2 TRIAL STEERING COMMITTEE 
A Trial Steering Committee (TSC) has not been convened for this study. An independent 
advisor has been appointed to oversee the conduct and progress of the study. 
11.3 DATA MONITORING COMMITTEE 
An independent Data Monitoring Committee (DMC) has not been convened for this study. 
11.4 INSPECTION OF RECORDS 
Investigators and institutions involved in the study will permit study related monitoring and 
audits on behalf of the sponsor, Research Ethics Committee (REC) review, and regulatory 
inspection(s).  In the event of an audit or monitoring process being implemented, the 
Investigators agree to allow the representatives of the sponsor direct access to all study 
records and source documentation. In the event of regulatory inspection, the CI agrees to 
allow inspectors direct access to all study records and source documentation. 
11.5 RISK ASSESSMENT 
An independent risk assessment may be performed by an Academic and Clinical Central 
Office for Research and Development (ACCORD) Clinical Trials Monitor to determine if 
monitoring is required and if so, at what level although this is unlikely as the study is not a 
CTIMP or high risk study. An independent risk assessment may also be carried out by the 
ACCORD Quality Assurance Group to determine if an audit should be performed 
before/during/after the study and if so, at what locations and at what frequency. 
11.6 STUDY MONITORING AND AUDIT 
An ACCORD Clinical Trials Monitor or an appointed monitor may visit the Investigator’s site 
prior to the start of the study and during the course of the study if required, in accordance with 
the monitoring plan if required. Risk assessment will determine if audit, by the ACCORD QA 
group, is required. Details will be captured in an audit plan. Audit of the Investigator’s site, 

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study management activities and study collaborative units, facilities and 3rd parties may be 
performed. 
12 
GOOD CLINICAL PRACTICE 
12.1 ETHICAL CONDUCT 
The study will be conducted in accordance with the principles of the International Conference 
on Harmonisation Guideline for Good Clinical Practice (ICH GCP) and the Research 
Governance Framework for Health and Community Care (Scotland) 2006 [9]. 
A favorable ethical opinion will be obtained from the appropriate REC and local Research and 
development (R&D) approval will be obtained prior to commencement of the study. 
12.2 INVESTIGATOR RESPONSIBILITIES 
The Principal Investigator is responsible for the overall conduct of the study at the site and 
compliance with the protocol and any protocol amendments.  In accordance with the 
principles of ICH GCP, the following areas listed in this section are also the responsibility of 
the Investigator.  Responsibilities may be delegated to an appropriate member of study site 
staff.   
12.2.1 Informed Consent 
The Principal Investigator is responsible for ensuring informed consent is obtained before any 
protocol specific procedures are carried out.  The decision of a participant to participate in 
clinical research is voluntary and should be based on a clear understanding of what is 
involved. 
Participants must receive adequate oral and written information – appropriate Participant 
Information and Informed Consent Forms will be provided.  The oral explanation to the 
participant will be performed by the Principal Investigator or qualified delegated person, and 
must cover all the elements specified in the Participant Information Sheet and Consent Form. 
The participant must be given every opportunity to clarify any points they do not understand 
and, if necessary, ask for more information.  The participant must be given sufficient time to 
consider the information provided.  It should be emphasised that the participant may withdraw 
their consent to participate at any time without loss of benefits to which they otherwise would 
be entitled. 
The participant will be informed and agree to their medical records being inspected by 
regulatory authorities and representatives of the sponsor(s) but understand that their name 
will not be disclosed outside the hospital. 
The Principal Investigator or delegated member of the study team and the participant will sign 
and date the Informed Consent Form to confirm that consent has been obtained.  The 
participant will receive a copy of this document and a copy filed in the Investigator Site File 
(ISF) and participant’s medical notes. 
12.2.2 Study Site Staff 
The Principal Investigator must be familiar with the protocol and the study requirements.  It is 
the Principal Investigator’s responsibility to ensure that all staff assisting with the study are 
adequately informed about the protocol and their study related duties. 
12.2.3 Data Recording 
The Principal Investigator is responsible for the quality of the data recorded in the CRF at the 
Investigator Site. 
12.2.4 GCP Training 
The Chief Investigator, Principal Investigators and Lead Research Nurse Co-ordinator should 
hold evidence of GCP training and ensure staff are aware of the guidelines.  All staff on the 
delegation log should have appropriate and relevant training in the research tasks that they 
undertake.   

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12.2.5 Confidentiality 
All evaluation forms, reports, and other records must be identified in a manner designed to 
maintain participant confidentiality.  All records must be kept in a secure storage area with 
limited access.  Clinical information will not be released without the written permission of the 
participant.  The Principal Investigators and study site staff involved with this study may not 
disclose or use for any purpose other than performance of the study, any data, record, or 
other unpublished, confidential information disclosed to those individuals for the purpose of 
the study.  Prior written agreement from the sponsor or its designee must be obtained for the 
disclosure of any said confidential information to other parties. 
12.2.6 Data Protection 
Data will be initially collected into a paper CRF and then entered into a specially designed 
password protected online accessed secure database (REDCAP; http://www.project-
redcap.org) the server of which is held within the University of Edinburgh. No participant 
identifiable information will leave the NHS or be entered onto REDCAP. Participants will be 
identified on REDCAP by study number alone. 
 
Identifiable electronic information will be kept in a separate database, which will not be 
accessible outside the immediate research team. This data will be linked by study number to 
the anonymised research database and will be stored on a secure, password protected 
location on the local hospital computer drive and only accessible to relevant staff. 
 
Identifiable non-electronic data of the participant will be kept in a locked filing cabinet in a 
locked local research study office.  
 
Data entry will be completed by the local research team and data analysis by the study 
statistician. No participant identifiable data will be transferred outwith the local NHS region. 
Participant identifiable data will be removed from electronic data being sent to the University 
of Edinburgh for analysis. 
 
The Chief Investigator will be responsible for the quality of the data recorded in the electronic 
CRF on the research database. 
All Investigators and study site staff involved with this study must comply with the 
requirements of the Data Protection Act 1998 with regard to the collection, storage, 
processing and disclosure of personal information and will uphold the Act’s core principles. 
Access to collated participant data will be restricted to those clinicians treating the 
participants, representatives of the sponsor and representatives of regulatory authorities. 
Computers used to collate the data will have limited access measures via user names and 
passwords. 
Published results will not contain any personal data that could allow identification of individual 
participants. 
13 
STUDY CONDUCT RESPONSIBILITIES 
13.1 PROTOCOL AMENDMENTS 
Any changes in research activity, except those necessary to remove an apparent, immediate 
hazard to the participant in the case of an urgent safety measure, must be reviewed and 
approved by the Chief Investigator.   
Amendments to the protocol must be submitted in writing to the appropriate REC and local 
R&D for approval prior to participants being enrolled into an amended protocol. 
13.2 PROTOCOL VIOLATIONS AND DEVIATIONS 
Prospective protocol deviations, i.e. protocol waivers, will not be approved by the sponsor and 
therefore will not be implemented, except where necessary to eliminate an immediate hazard 
to study participants. If this necessitates a subsequent protocol amendment, this should be 
submitted to the REC and local R&D for review and approval if appropriate. 

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Protocol deviations will be recorded in a protocol deviation log and logs will be submitted to 
the sponsors every 3 months. Each protocol violation will be reported to the sponsor within 24 
hours of becoming aware of the violation. 
13.3 SERIOUS BREACH REQUIREMENTS 
A serious breach is a breach, which is likely to affect to a significant degree: 
(a) the safety or physical or mental integrity of the participants of the study; or 
(b) the scientific value of the study. 
If a potential serious breach is identified by the Chief investigator, Principal Investigator or 
delegates, the sponsors (accord.seriousbreach@ed.ac.uk) must be notified within 24 hours.  
It is the responsibility of the sponsors to assess the impact of the breach on the scientific 
value of the study, to determine whether the incident constitutes a serious breach and report 
to regulatory authorities and research ethics committees as necessary.  
13.4 STUDY RECORD RETENTION 
All study documentation will be kept for a minimum of 5 years from the protocol defined end of 
study point. When the minimum retention period has elapsed, study documentation will not be 
destroyed without permission from the sponsor. 
13.5 END OF STUDY 
Clinical interventions expected to finish 31/12/2017. End of the study will be once final 
analysis has been completed. 
The Investigators and sponsor have the right at any time to terminate the study for clinical or 
administrative reasons.  
The end of the study will be reported to the REC within 90 days, or 15 days if the study is 
terminated prematurely.  The Investigators will inform participants of the premature study 
closure and ensure that the appropriate follow up is arranged for all participants involved. 
A summary report of the study will be provided to the REC within 1 year of the end of the 
study. 
13.6 INSURANCE AND INDEMNITY 
The sponsor is responsible for ensuring proper provision has been made for insurance or 
indemnity to cover their liability and the liability of the CI and staff.  The sponsor, as part of the 
United Kingdom’s Nation Health Service, and will have the benefit of NHS Indemnity. 
14 
REPORTING, PUBLICATIONS AND NOTIFICATION OF 
RESULTS 
14.1 AUTHORSHIP POLICY 
Ownership of the data arising from this study resides with the study team.  On completion of 
the study, the study data will be analysed and tabulated, and a clinical study report will be 
prepared in accordance with ICH guidelines.  
14.2 PUBLICATION 
The results of our research will be disseminated in the following ways: 
1. Summary disseminated to NHS Lothian communication systems including EMERGE 
intra- and internet sites and all participating sites 
2. A media summary  
3. Presentation at local and national educational, clinical and research meetings and 
international research meetings 
4. Publication in peer reviewed journals  
5. Research report disseminated to NHS Lothian R&D, NHS Research Scotland, and 
CHSS. 

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The clinical study report will be used for publication and presentation at scientific meetings. 
Investigators have the right to publish orally or in writing the results of the study. 
14.3 PEER REVIEW 
The IPED study received grant funding from CHSS where it underwent peer review and was 
successfully awarded funding. The patient information sheet, consent form and patient 
symptom diary and patient satisfaction and compliance questionnaire were reviewed by the 
EMERGE patient and public involvement group. 
 
 

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15 
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