Utility of a Smart Phone Application in Assessing Radial Artery Patency - the CAPITAL iRADIAL Study
Phase: NA
Conditions: Coronary Heart Disease
Sponsor: Ottawa Heart Institute Research Corporation

RESEARCH PROTOCOL - Utility of a Smart Phone Application in Assessing Radial Artery 
Patency - the CAPITAL iRADIAL Study 
Protocol Number: 20150116-01H 
Version: 1 
Date: February 28, 2015 
Principal Investigator: 
Dr. Benjamin Hibbert MD, PhD, FRCPC 
University of Ottawa Heart Institute 
Assistant Professor in Cardiology and Clinician Scientist 
Division of Cardiology 
40 Ruskin Street, Room H-4238  
Ottawa, Ontario 
K1Y 4W7 
613-761-5128
Appendix to: Di Santo P,  Harnett DT, Simard T, et al. Photoplethysmography using a smartphone application for assessment of ulnar artery 
patency: a randomized clinical trial. CMAJ 2018. doi: 10.1503/cmaj.170432. Copyright © 2018 The Author(s) or their employer(s).
To receive this resource in an accessible format, please contact us at cmajgroup@cmaj.ca.

Utility of a Smart Phone Application in Assessing Radial Artery Patency - the 
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TABLE OF CONTENTS 
1. LIST OF ABBREVIATIONS .................................................................................................... 3 
2. INTRODUCTION ................................................................................................................... 3 
2.1 Lay Summary ................................................................................................................... 3 
2.2 Rationale & Study Aim ...................................................................................................... 3 
3. METHODS ............................................................................................................................. 4 
3.1 Study design and methodology ......................................................................................... 4 
Modified Allen’s test ............................................................................................................ 4 
iPhone plethysmography application ................................................................................... 4 
Conventional plethysmography (i.e. Barbeau test) .............................................................. 4 
Doppler Ultrasound imaging ................................................................................................ 4 
3.2 Participant Identification and Recruitment ......................................................................... 4 
3.3 Inclusion Criteria ............................................................................................................... 4 
3.4 Exclusion Criteria .............................................................................................................. 5 
3.5 Consent ............................................................................................................................ 5 
3.6 Outcomes ......................................................................................................................... 5 
3.7 Withdrawal from Study/Early Termination ......................................................................... 5 
4. STUDY RISKS ....................................................................................................................... 5 
5. SAFETY REPORTING ........................................................................................................... 5 
6. DATA CAPTURE, SAMPLE SIZE AND STATISTICAL ANALYSIS ........................................ 6 
6.1 Data Capture .................................................................................................................... 6 
6.2 Sample Size ..................................................................................................................... 6 
6.3 Statistical Analysis ............................................................................................................ 6 
7. ETHICAL CONSIDERATIONS ............................................................................................... 6 
8. CONFLICT(S) OF INTEREST ................................................................................................ 6 
9. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS .......................................................... 6 
10. DATA HANDLING AND RECORD KEEPING ....................................................................... 7 
11. PUBLICATION POLICY ....................................................................................................... 7 
12. RESEARCH TEAM .............................................................................................................. 7 
13.1 Principal Investigator ...................................................................................................... 7 
13.2 Co-investigators/Study Staff ........................................................................................... 7 

Utility of a Smart Phone Application in Assessing Radial Artery Patency - the 
CAPITAL iRADIAL Study 
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1. LIST OF ABBREVIATIONS
AE: Adverse events 
DUS: Doppler ultrasound 
MAT: modified Allen’s test 
SAE: Serious adverse events 
2. INTRODUCTION
2.1 Lay Summary  
Accessing the arteries of the heart through the blood vessels of the wrist is becoming 
increasingly popular. By obtaining access via the artery in the arm as opposed to the groin, 
there is less risk of complications and improved patient satisfaction. However, using the wrist 
can cause blockage of the artery after the procedure. If there is too little blood flow from a 
second artery that supplies the hand, this could result in significant injury. Therefore, it is 
important to test these blood vessels in the wrist prior to having this procedure. The best way to 
evaluate these arteries involves the use of ultrasounds but this takes a long time and is 
expensive. Therefore, the artery is usually evaluated with a clinical test known as the modified 
Allen’s test, which relies on the doctor watching the flushing of the hand during compression of 
the artery. Currently smart phones with cameras are able to assess blood flow by passing light 
through the skin and watching differences in brightness. This may be a better way to assess the 
arteries in the hand as it is less subjective than simply watching the flushing of the hand. This 
study aims to assess the ability of an iPhone application in determining whether there is 
sufficient blood flow through the arteries of the wrist and comparing it to both the clinical test 
and the ultrasound.  
2.2 Rationale & Study Aim 
Over the past decade, the transradial approach to cardiac catheterization has emerged as the 
preferred method of angiography and intervention. There have been several observational and 
randomized controlled trials which have shown an association between transradial access and 
reduced risk of bleeding and other vascular complications, increased cost-effectiveness, 
improved patient satisfaction, and a mortality benefit in high-risk patient populations. However, 
this technique does carry risks of complications including radial artery injury (i.e. occlusion, non-
occlusive injury, spasm, hand ischemia, pseudoaneurysm, perforation), nerve damage, 
arteriovenous fistulisation, and bleeding. Radial artery occlusion is the most common adverse 
outcome. In individuals with intact collateral palmar circulation from the ulnar artery, they are 
usually asymptomatic and do not require further intervention. However, if an individual lacks 
adequate collateral circulation, they are at risk of hand ischemia and loss of tissue or function 
necessitating surgical intervention or, ultimately, amputation.  Thus, it is important to assess 
competency of the collateral palmar circulation prior to transradial cardiac catheterization to 
mitigate the risks associated with this approach. 
The gold standard evaluation of collateral circulation involves the use of colour Doppler 
ultrasound imaging of radial and ulnar arteries which allows for direct, objective assessment of 
arterial patency and competency through direct visualization of blood flow. The use of pre-
procedural ultrasound remains both labour and resource intensive and hence is not feasible for 
practical use, therefore we must rely on clinical assessment of collateral circulation. This has 
been traditionally evaluated through use of the modified Allen’s test (MAT), a technique 
performed at the bedside as part of the pre-procedural physical examination. More recently, the 
introduction of plethysmography and pulse oximetry (i.e. the Barbeau test) have been utilized to 
theoretically provide a more objective measure of assessing collateral circulation, though these 
too are limited by the available resources.  

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Protocol V1: February 28, 2015 
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Given the ever increasing prevalence of smart phones, this study aims to address the utility and 
feasibility of an iPhone application in determining adequacy of collateral palmar circulation. 
Should this iPhone application provide diagnostic accuracy, it could quickly become an 
alternative method of providing an objective measure of collateral palmar circulation rather than 
relying on the subjective MAT.  
3. METHODS
3.1 Study design and methodology 
For this study, we will be recruiting a total of approximately 450 patients over one year, 
beginning in March 2015. Patients will be randomized in a 1:1 fashion to the MAT or iPhone-
based assessment using concealed envelopes prepared using a computer random sequence 
generator by the principal investigator. All subjects will also undergo plethysmography (Barbeau 
and reverse Barbeau) and Doppler ultrasound studies of the radial and ulnar artery. 
Modified Allen’s test 
-
The investigator will apply pressure to the participant’s wrist to compress both the
radial and ulnar arteries
-
Participant will be asked to make a fist several times
-
Participant will then be asked to keep their hand open while the investigator releases
the pressure over one of the arteries
-
This will then be repeated once more on the same arm by releasing the opposite
artery, as well as on the radial and ulnar arteries on the opposite arm
iPhone plethysmography application 
-
The investigator will apply the camera lens of an iPhone to the participant’s thumb
-
The investigator will then apply pressure to the participant’s wrist to compress either
the radial or ulnar artery in isolation for up to two minutes
-
This will then be repeated once more on the same arm by releasing the opposite
artery, as well as on the radial and ulnar arteries on the opposite arm
Conventional plethysmography (i.e. Barbeau test) 
-
The investigator will apply a standard clamp sensor on the participant’s thumb
-
The investigator will then apply pressure to the participant’s wrist to compress either
the radial or ulnar artery in isolation for up to two minutes
-
This will then be repeated once more on the same arm by releasing the opposite
artery, as well as on the radial and ulnar arteries on the opposite arm
Doppler Ultrasound imaging 
-
The investigator will apply a small amount of ultrasound gel and an ultrasound probe
to the participant’s wrist at 1cm proximal to the radial head
3.2 Participant Identification and Recruitment 
Prospective research participants will be patients planned to undergo coronary angiography or 
who have undergone angiography in the Coronary Care Unit (CCU) and reference center, day 
unit, cardiology clinic, as well as the H3, H4 and H5 inpatient wards at the University of Ottawa 
Heart Institute will be recruited. 
3.3 Inclusion Criteria 
All persons who are patients who are greater than 18 years of age at the University of Ottawa 
Heart Institute and are candidates for coronary angiography. 

Utility of a Smart Phone Application in Assessing Radial Artery Patency - the 
CAPITAL iRADIAL Study 
Protocol V1: February 28, 2015 
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3.4 Exclusion Criteria 
Exclusion criteria include hemodynamic instability, need for emergent angiography (active chest 
pain or STEMI), inability or unwillingness to provide informed consent and known surgical 
removal of the radial or ulnar artery. If the patient had undergone transradial access in the 
preceding week, the assessment and ultrasound were performed on the contralateral limb and 
the accessed limb was excluded to avoid discomfort.  
3.5 Consent 
Only patients who have signed their consent to have their records reviewed for research will be 
approached. It will be the responsibility of the health care team to approach the patient for 
consent to review their record. A co-investigator or study staff member will review the consent 
process with the patients and obtain informed consent. This will be performed by ensuring the 
patient is able to understand and appreciate the implications of participating in the study as well 
as the risks and benefits of their involvement. The written informed consent form will be 
provided and once reviewed, questions will be answered. 
3.6 Outcomes 
The primary outcome of this study is the overall diagnostic accuracy of the iPhone application or 
MAT in assessing the competency of collateral blood supply to the hand compared with DUS. 
Though both left and right radial vascular access sites will be assessed when available in all 
patients, in clinical practice the right radial artery (RRA) is preferentially used. The RRA will 
therefore be defined as the potential primary access site except in patients who have no 
palpable right radial pulse, previous RRA graft harvests, recent or ongoing arterial access in that 
artery (e.g. invasive hemodynamic monitoring or arterial stab for blood gas analysis), or an 
arteriovenous fistula in the right upper extremity in which cases the left radial artery (LRA) will 
be selected.  
The secondary endpoint is the diagnostic accuracy of the iPhone application for radial or ulnar 
artery patency using results from both right and left arteries (irrespective of expected primary 
access site). Prespecified variables (i.e. age, sex, BMI, and presence of a palpable pulse) will 
be used to determine predictors of poor diagnostic performance. Additionally, the diagnostic 
accuracy of the HRMA will be compared to that of conventional plethysmography. 
3.7 Withdrawal from Study/Early Termination 
Participants may withdraw from the study at any time without penalty or prejudice. Participants 
may be withdrawn from the study if: 
•
The participant fails to comply with the requirements of the study.
•
The study doctor feels it is in the best interest of the participant.
•
Participant needs additional treatment that would interfere with the study.
4. STUDY RISKS
Participants may experience very mild discomfort with compression of the radial and ulnar 
arteries while performing the tests. 
5. SAFETY REPORTING
Adverse events (AE) and Serious Adverse Events (SAE) will be defined and reported according 
to ICH GCP and Regulatory standards. AEs and SAEs will be reported from the signing of the 
consent and followed until resolution. 

Utility of a Smart Phone Application in Assessing Radial Artery Patency - the 
CAPITAL iRADIAL Study 
6. DATA CAPTURE, SAMPLE SIZE AND STATISTICAL ANALYSIS
6.1 Data Capture 
The patient's medical record will be reviewed to obtain information regarding demographic 
information (e.g. gender, age, height, weight, body mass index, ethnicity), cardiac risk factors 
(e.g. hypertension, diabetes, smoking, family history of heart disease, hyperlipidemia, previous 
myocardial infarction, previous cardiac intervention, previous strokes), past medical history, and 
current medications. The results of the four  
6.2 Sample Size 
Assuming a diagnostic accuracy of 80% using the MAT, in order to achieve an 80% power to 
detect a 10% difference in diagnostic accuracy using the iPhone application, a sample size of 
438 participants was calculated. 
6.3 Statistical Analysis  
All continuous variables will be reported as mean ± standard deviation. Categorical variables will 
be described as number (%). Comparisons between diagnostic arms will be performed using 
chi-square or Fisher’s exact tests. Within arm comparisons will be performed using McNemar’s 
tests when comparing proportions for paired data. Artery level data will be analysed using 
generalized estimating equations. Logistic regression will be used to generate the model for 
predictors of false positive assessment. All calculations will be performed using SAS v9.4 (SAS 
Institute Inc., Cary, NC). 
7. ETHICAL CONSIDERATIONS
The investigator will ensure that this study is conducted in full conformance with the principles of 
the “Declaration of Helsinki” or with the laws and regulations of the country in which the 
research is conducted, whichever affords the greater protection to the individual. The study will 
fully adhere to the principles outlined in “Guideline for Good Clinical Practice” ICH Tripartite 
Guideline or with local law if it affords greater protection to the patient. It is the responsibility of 
the investigator, or a person designated by the investigator to obtain signed informed consent 
from each patient prior to participating in this study after adequate explanation of the aims, 
methods, anticipated benefits, and potential hazards of the study. The investigator or designee 
will also explain that the patients are completely free to refuse to enter the study or to withdraw 
from it at any time, for any reason. If new safety information results in significant changes in the 
risk/benefit assessment, the consent form will be reviewed and updated if necessary.  
The protocol, informed consent and any accompanying material provided to the patient will be 
submitted by the investigator to an IRB for review. An approval letter or certificate (specifying 
the protocol number and title) from the IRB must be obtained before study initiation by the 
investigator specifying the date on which the committee met and granted the approval. This 
applies whenever subsequent amendments/modifications are made to the protocol. Any 
modifications made to the protocol, informed consent or material provided to the patient after 
receipt of the IRB approval must also be submitted by the investigator in accordance with local 
procedures and regulatory requirements. 
8. CONFLICT(S) OF INTEREST
None to declare. 
9. DIRECT ACCESS TO SOURCE DATA/DOCUMENTS
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Utility of a Smart Phone Application in Assessing Radial Artery Patency - the 
CAPITAL iRADIAL Study 
The Investigator and the study centre will accept responsibility of monitoring and auditing as 
well as inspections by the Ottawa Health Science Network Research Ethics Board and the 
University of Ottawa Heart Institute. They will also provide all study-related records, as well as 
source documents to these instances when they are requested to. The confidentiality of the 
participant’s identity shall be well protected and consistent with local and national regulations 
when the source documents are subject to direct access. 
10. DATA HANDLING AND RECORD KEEPING
The Investigator will maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into two different separate categories: [1] Investigator's Study File and [2] patient 
clinical source documents. The Investigator's Study File will contain the protocol/amendments, 
CRF/DCS and schedule of assessments, Independent Ethics Committee/Institutional Review 
Board approval with correspondence, sample informed consent, staff curriculum vitae and 
authorization forms and other appropriate documents/correspondence, etc.  
Patient clinical source documents will include patient hospital/clinic records, physician's and 
nurse's notes, appointment book, original laboratory reports, special assessment reports, signed 
informed consent forms. All personal health information collected will be kept confidential unless 
release is required by law. For audit purposes only, the Ottawa Health Science Network 
Research Ethics Board and the University of Ottawa Heart Institute may review the patients’ 
medical records under the supervision of Dr. Benjamin Hibbert and his staff. The Master list 
containing the patients’ personal health information will be kept separate from the patient 
screening and enrollment logs. The Master List which links the patient with the independent 
study number will only be accessible by Dr. Benjamin Hibbert and his staff. The master link and 
study files will be stored separately and securely. 
All paper records will be stored in a locked filing cabinet and /or office. All electronic records, 
including the Master List, will be stored on a secure internal hospital server and password 
protected, again only accessible by Dr. Benjamin Hibbert and his staff. No identifiable 
information will be stored on any mobile devices (laptops, USB keys, CDS, DVDs, etc). The 
Investigator must keep source documents as described above on file for 10 years after 
completion or discontinuation of the study. After that period of time the documents may be 
destroyed, according to local regulations.   
11. PUBLICATION POLICY
In accordance with standard editorial and ethical practice, the results of this study will be 
published or presented at congresses or scientific meetings. Patients will not be identifiable in 
any publications or presentations. 
12. RESEARCH TEAM
13.1 Principal Investigator 
Dr. Benjamin Hibbert 
13.2 Co-investigators/Study Staff 
Dr. Aun-Yeong Chong  
Dr. Pietro Di Santo 
Dr. David Harnett 
Dr. Derek So  
Dr. Marino Labinaz 
Dr. Michel Le May 
Dr. Alexander Dick 
Dr. Trevor Simard 
Dr. F. Daniel Ramirez 
Dr. Ali Pourdjabbar 
Dr. Altayyeb Yousef 
Dr. Robert Moreland 
Dr. George Wells 
Dr. Jaya Chandrashekar 
Dr. Roxana Mehran 
Protocol V1: February 28, 2015
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Utility of a Smart Phone Application in Assessing Radial Artery Patency - the 
CAPITAL iRADIAL Study 
Jordan Bernick 
Richard Jung 
Pouya Motazedian 
Protocol V1: February 28, 2015 
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