Connected Health Blood Pressure Monitoring In Stroke and TIA Patients
Phase: NA
Conditions: Stroke, Ischemic Attack, Transient
Sponsor: University of Pennsylvania

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IRB APPLICATION 
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Application for Review of Human Research: IRB Protocol Summary 
Biomedical Research 
Section II 
 
 
Principal Investigator: Michael T. Mullen, M.D. 
 
PROTOCOL TITLE 
1.  Full Title  
Connected Health Blood Pressure Monitoring In Stroke and TIA Patients  
 
 
2.  Brief Title 
Connected BP Study 
 
STUDY SPONSORSHIP 
1.  Funding Sponsor 
Penn Medicine Center for Healthcare innovation 
 
2.  Primary Sponsor 
 
 

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Study Summary 
The goal of this pilot project is to assess adherence with home blood pressure monitoring in hypertensive patients 
with a history of stroke and to determine if a social incentive improves adherence with monitoring.  Enrolled 
subjects stroke (Ischemic stroke, intraparenchymal hemorrhage, or high-risk TIA)and uncontrolled blood pressure, 
defined by SBP>140 or DBP>90 mm Hg at the time of study screening.  To be eligible subjects will also be 
required to own a smart phone (iOS or Android operating system).  After enrollment, patients will be given a home 
blood pressure cuff with instructions to monitor their BP twice daily for 90 days.  Subjects will be randomly 
assigned to a social incentive program, in which a social supporter receives updates via email and/or text 
message on the subject’s adherence with BP monitoring and their average blood pressure.  This study will 
provide important pilot data which will inform the design of future studies utilizing connected health and automated 
systems to improve home blood pressure monitoring and blood pressure control in patients with a history of 
stroke.   
 
1.  STUDY OBJECTIVES 
1.1  Primary Objective 
The primary objective of this pilot study is to quantify adherence to 90 days of home blood pressure monitoring 
and to determine if a social incentive improves adherence.   
1.2  Secondary Objective 
A secondary objective of this study is to determine if adherence with blood pressure monitoring is associated with 
change in blood pressure during the study period and to determine which individual factors are associated with 
adherence.    
 
2.  OUTCOME VARIABLES  
2.1  Primary Endpoint 
Adherence with home blood pressure monitoring, defined by the proportion of home blood pressure recordings 
successfully completed.   
2.2  Secondary Endpoints 
Secondary endpoints include the following: 
 
Change in blood pressure over the 90 day study period 
 
Number of physician visits 
 
Number of emergency department visits 
 
Number of phone calls to the study team 
 
Number of changes in antihypertensive medications (dose adjustment or addition of a new agent) 
 
Patients perception of blood pressure monitoring device ease of use  
 
Patients perception of the utility of blood pressure monitoring  
 
Patients perception of blood pressure control  
 

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3.  BACKGROUND 
Stroke is the fourth leading cause of death and a leading cause of adult disability in the US, with over 800,000 
cases per year.1 Total direct and indirect costs from stroke are expected to increase from 72 Billion in 2012 to 183 
Billion in 2030.2 Effective secondary prevention strategies exist, including blood pressure control, high dose statin 
therapy, smoking cessation, diet, and exercise. The goal of this proposal is to perform important preliminary work 
on the feasibility of connected health and behavioral/social incentives to improve blood pressure control in 
patients with TIA or stroke.   
 
Hypertension is by far the most significant risk factor for both ischemic stroke and intracerebral hemorrhage, with 
a population attributable risk of 35 to 75% depending on the definition of hypertension used.3 Approximately half 
of hypertensive patients with stroke continue to have suboptimally controlled blood pressure levels, and prior work 
suggests that stroke patients are even less likely to achieve target blood pressure goals than patients with 
coronary artery disease.4  Importantly, treatment to lower blood pressure reduces future stroke in those with and 
without a prior history of stroke.5-7  In a study of 227 ischemic stroke patients with symptomatic intracranial 
stenosis and a median follow-up of 32 months, 17% of subjects who achieved a systolic blood pressure of <140 
(or <130 for diabetics) had a recurrent stroke, MI, or vascular death, compared to 29% in patients who did not 
achieve goal blood pressure.8 All of these 227 patients were all enrolled in a clinical trial and were receiving 
protocol driven intensive medical therapy to optimize risk factor control.  Despite this, only 121 of 227 (53%) 
reached their goal blood pressure.   
 
Non-adherence to prescribed medications has been proposed as one major reason for suboptimal blood pressure 
control.9   In one study of 4068 elderly subjects with hypertension, antihypertensive prescriptions were filled for 
only 49% of the prescribed medication days, and only 23% of subjects had good compliance (defined as taking > 
80% of their recommended medication regimen).9 Additionally, lack of insight into the benefit of aggressive blood 
pressure control, lack of awareness of actual blood pressure levels, and lack of effective strategies for triggering 
more intensive therapy for both patients and providers may all be important.10   
 
One prior study compared home blood pressure monitoring with intermittent nurse support to usual care in 
patients with recent stroke.11 At 12 month follow-up, more patients in the intervention group had changes to their 
antihypertensive therapy (60% vs. 48%, p=0.02), but there was no overall difference in change in mean systolic 
blood pressure from baseline to 12 month measurements.  This study was limited in that the incentive (nursing 
support) is relatively resource intensive, patient report was used to assess compliance rather than automated 
device recording, and blood pressure was checked infrequently (weekly).    
 
The proposed study builds on existing literature in several unique and important ways.  First, the blood pressure 
monitor used in this study is a commercially available unit that will interact with the subject’s smart phone.  
Software that comes with the device will allow the subject to track their own blood pressure. Blood pressure will 
be checked more frequently (twice daily).  Finally, the incentive used in this study will provide real time feedback 
to the subject and to a social supporter that they identify, in an effort to improve adherence.   
 
4.  CHARACTERISTICS OF THE STUDY POPULATION 
4.1  Target Population 
Adult subjects with a history of acute ischemic stroke, intraparenchymal hemorrhage, or high risk transient 
ischemic attack (TIA) and uncontrolled hypertension, defined by SBP>140 mm Hg or DBP > 90 mm Hg.       
4.2  Accrual 
The study will enroll a total of 90 patients at the Hospital of the University of Pennsylvania (HUP).   
 

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The study will be powered on the primary objective of the study, which is to compare adherence with twice daily 
blood pressure monitoring in subjects with and without a social incentive.  Based on data in other study 
populations, we expect a 50% adherence rate in subjects without a social incentive.   
 
A sample size of 90 subjects will provide 80% power to detect a 30% difference in adherence between groups. 
This calculation is based on a two-sample comparison of means, with alpha=0.05.   
 
Patients will be identified from the inpatient stroke service and the outpatient neurology clinic at the Hospital of the 
University of Pennsylvania.  It is expected that we will complete enrollment in 15 months and the study will be 
completed in 2 years.     
4.3  Inclusion Criteria 
1. Adult, age ≥ 18 years 
2. History of ischemic stroke, intraparenchymal hemorrhage, or high risk TIA (defined by ABCD2 ≥ 4) with 
the past 5 years prior to enrollment 
3. Hypertensive at time of screening, defined by SBP>140 mm Hg or DBP >90 mm Hg 
4. Enrollment must occur within 30 days of study screening 
5. Must own a smart phone capable of interacting with the connected blood pressure cuff (Apple iPhone 
3GS or higher; Android 4.0 or higher with Bluetooth connectivity)   
6. Must be able to identify at least one adult (≥18) with internet access and/or a smart phone with text 
messaging capability who could serve as a social support person. 
7. Willingness and ability to sign informed consent by patient  
4.4  Exclusion Criteria 
1. Moderate or severe disability, defined by modified Rankin Scale ≥ 3. 
2. Moderate or severe cognitive impairment, defined by a Mini-Mental Status Examination Score of ≤20 
3. Expected residence in a rehabilitation hospital, nursing facility or assisted living community during the 
study period.   
4. Upper arm circumference <9 inches or >17 inches 
5. Inability to monitor BP in upper arms (i.e. history of bilateral radical mastectomy, bilateral severe 
subclavian stenosis, or bilateral arterial venous fistulas for dialysis).   
6. Inability to follow-up at 90 days and return BP monitor 
7. Active participation in another clinical trial  
8. Pregnant women 
4.5  Vulnerable Populations  
Children, fetuses, neonates, prisoners and pregnant women are not included in this research study.  
4.6  Subject Recruitment  
 
4.6.1  Participant Screening and Recruitment 
Potential study participants will be identified from the inpatient stroke service at the Hospital of the University of 
Pennsylvania and the outpatient neurology clinic at the Hospital of the University of Pennsylvania. Additionally, 
the neurology residents and the stroke physicians at the Hospital of the University of Pennsylvania will be 

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informed of the study and provided with contact info for study personnel to refer eligible outpatients.  The 
attending physician caring for the patient will be informed of eligible patients prior to enrollment. Screening visits 
may include an inpatient admission for stroke or TIA or any routine outpatient clinic visits in which blood pressure 
is measured.  Inpatients who are considered for the study can only be enrolled if they are being discharged to 
home, and enrollment should occur on the date of discharge.  Patients discharged to an inpatient rehabilitation 
hospital or skilled nursing facility are excluded from participation.   
 
4.6.2  Informed Consent  
Informed consent must be obtained (completed online by the participant) prior to initiation of any study-related 
activity. Consent will be obtained via the Way to Health online platform.  Way to Health is secure and HIPAA 
compliant.   
4.6.3  Consent Process 
After an eligible subject is identified, a member of the study team will contact the attending physician responsible 
for the patient’s care to ensure that the patient is clinically suitable for the study.  If so, the patient will be 
approached by a member of the research team for consent.  The full consent form is enclosed as attachment 1.  
The consent form will be described to the patient in plain language.  The patient will also be given a copy of the 
consent form for their reference. Electronic informed consent will be obtained via the Way to Health platform prior 
to the onset of any study related activities.  The patient will have the ability to withdraw consent and exit the study 
at any time.   
 
The physicians caring for the patient clinically will make judgments about capacity.  All patients seen by neurology 
receive detailed neurologic examinations, which can be used to assess capacity.  These examinations include an 
assessment of cognition, language function, and neglect/anosagnosia in addition to other domains of neurologic 
function.  Additionally, the person obtaining consent will evaluate the subjects understanding of the risks/benefits 
of study participation by asking open-ended questions about the study and addressing any misperceptions or 
unanswered questions.  Possible questions include: Can you describe the study in your own words?  What more 
would you like to know?  Would you please explain to me what we are asking you to do?  What are your 
concerns?  If a potential subject is not competent to consent for him or herself, they will be excluded from the 
study.  
4.6.4  Waiver of Authorization 
Not applicable 
 
 
4.6.5  HIPAA Authorization 
Following mandated federal HIPAA regulations and according to local IRB guidelines, the use and disclosure of 
the subject’s protected health information (PHI) will be explained and participant authorization will be obtained as 
part of the informed consent process. The consent forms will list those individuals and organizations that may 
have access to the participant’s research data.  HIPAA authorization will be included in the informed consent 
process.  The HIPAA authorization form is attached as a part of the informed consent form in attachment 1.   
 
4.6.6 Patient Flow 
A depiction of patient flow is presented below: 
 

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4.6.7 Follow-up Period 
Participants will have a follow-up phone call at 48-72 hours after enrollment and either a phone or computer 
based encounter 30 days +/- 3 days after enrollment and an in-person visit at 90 days +/-7 days.  Participation will 
be completed after the day 90 visit.    
5.  STUDY DESIGN 
5.1  Phase 
Phase 2 pilot trial.   
5.2  Design 
This is a single center randomized trial designed to assess the effectiveness of a social intervention to improve 
adherence with home blood pressure monitoring.  Computer-based block randomization (block size=4) will be 
used to maintain relatively equal numbers of subjects in both arms of the study.  This study will provide important 
preliminary data for future studies, which will use behavioral incentives to improve adherence to home blood 
pressure monitoring and titration of antihypertensive therapy.   
5.3  Study Duration  
Individual subjects will be in the study for a total of 90 days. They will receive a telephone call at 48 hours and 
either a computer based or telephone based interview at 30+/- 3 days and then will have an in-person visit at 
90+/-7 days.     
 
Total study duration is expected to last approximately 2 years.  We expect to enroll about 6 subjects per month 
and should reach our target of 90 patients by 15 months.  The final follow-up visit will occur 3 months after the last 
patient is enrolled.  Data collection and analysis will be completed in the subsequent 6 months for total study 
duration of 24 months.     
 
6. DRUGS OR DEVICES  
 
All patients will receive a Withings wireless blood pressure monitor.  This commercially 
available device measures heart rate and blood pressure.  The device is operated by 
and communicates with both Apple and Android smart phones (Apple iPhone 3GS and 
newer, Android 4.0 and newer) via bluetooth.  Blood pressure and heart rate readings 
will be automatically uploaded to Penn’s Way to Health platform via the subject’s smart 
phone.  There are no risks associated with this device.  All subjects will be instructed 
on the proper use of the device as well as best practices for measuring blood pressure at the time of study 
enrollment.   
 

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Way to Health is an integrated research platform that uses online tools to connect with and collect data from 
wireless devices.  Blood pressure and heart rate data will be collected and stored in a secure, HIPAA complaint 
format.  The platform will provide automatic reminders for all patients to use the blood pressure cuff twice daily.  
Additionally, the platform will automatically apply the social incentive to randomized subjects.  The social incentive 
is described in more detail later (section 7.1).   
 
7.  STUDY PROCEDURES 
7.1  ENROLLMENT 
At the time of enrollment the following data will be collected: Age, sex, race, ethnicity, handedness (left arm 
dominate, right arm dominate), date of stroke, etiology of stroke (large vessel disease, small vessel disease, 
cardioembolic, other defined etiology, cryptogenic), past medical history (including prior history of: hypertension, 
diabetes, hyperlipidemia, atrial fibrillation, congestive heart failure, 
coronary artery disease and/or myocardial infarction, chronic kidney 
disease, peripheral artery disease, stroke prior to the enrolling event, and 
other), current medications, smoking history (current, former, never 
smoker), employment status (currently employed, disabled, retired), living 
situation (lives alone yes/no, if no, number of people and relationship of 
people living in the home), annual household income (<$20,000, $20,000-
39,999, $40,000-64,999, $65,000-104,999, $105,000+), insurance status 
(private health insurance, medicare, medicaid, none), primary care 
provider (yes/no), cardiologist (yes/no), nephrologist (yes/no).  We will also obtain contact information for follow-
up phone calls and for scheduling the 90 day visit.  Social security numbers will be collected for subject 
reimbursement purposes.  
Study Measurements at enrollment 
1. Upper arm circumference.  Measured using a tape measure in the mid-portion of the upper arm.  
Circumference <9” or >17” is an exclusion criteria.   
 
2. Mini-Mental Status Examination (MMSE) – the MMSE is a brief, standardized cognitive assessment . 
Subjects will be excluded if they score ≤ 20 on the MMSE, which corresponds to moderate or severe 
dementia. 
2.  Modified Rankin Scale (mRS).  The mRS is a 5 point scale which 
ranges from no disability to severe disability (figure 1).  It is assessed 
using a brief, structured interview.  Study personnel will be trained and 
certified in the use of the mRS.  Subjects with mRS >2 are excluded.  
 
3.  National Institute of Health Stroke Scale (NIHSS).  The NIHSS is a 
brief, structured neurologic examination, designed to assess deficits 
from stroke (figure 2).  Study personnel will be trained and certified in 
the use of the NIHSS.   
 
4.  Heart Rate and blood pressure – Heart rate and blood pressure will 
be measured at least 30 minutes after exercise.  The patient will have 
been sitting for at least 5 minutes before blood pressure is checked.  
The patient will be asked to sit in a chair with their back straight and 
supported and their feet flat on the floor.  The arm will be supported on 
a flat surface at approximately the level of the heart.  Blood pressure 
and heart rate will be assessed in the non-dominate arm using an 
Modified Rankin Scale 
0 – No symptoms 
1 – No disability; able to carry out all  
      previous activities despite some symptoms 
2 – Slight disability; unable to carry out all previous activities  
      but able to look after own affairs  
3 – Moderate disability; requires some help but able to walk  
      unassisted 
4 – Moderately severe disability; unable to attend to own  
      bodily needs and unable to walk unassisted. 
5 – Severe disability; requires constant nursing care and  
      attention, bedridden.  
Figure 1. Modified Rankin Scale 
Figure 2. NIH Stroke Scale 

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automated sphygmomanometer.  This will be repeated for a total of three measurements, which will be averaged 
to determine the baseline blood pressure.   
 
 
Education 
At the time of enrollment, the patient will receive general education about hypertension, including proper 
technique for blood pressure measurement, goal blood pressure, and appropriate actions to take if blood pressure 
is severely elevated or abnormally low.  Additionally patients will be educated on the proper use of the Withings 
Blood Pressure monitor.  The appropriate software will be downloaded onto their smart phone and they will be 
supervised as they measure their own blood pressure with the device.  Subjects will be encouraged to measure 
blood pressure in their non-dominate arm for ease of monitor placement.   Subjects will be instructed to take their 
BP prior to or at least 2 hours after moderate or high intensity exercise.  Subjects will be instructed to take their 
BP twice daily, once between 6:00am-11:59am and once between 4:00pm-9:59pm.    Finally, patients will be 
enrolled onto the Way to Health platform and will choose whether they prefer to receive study communications via 
email or text message. The subject will also be given a telephone number that they may call if they encounter any 
technical difficulties with the Withings device.   
 
Connected Health Monitoring 
The Withings blood pressure cuff provides the subject with a graphical display of their blood pressure after it is 
measured as well as prior blood pressure readings.  Blood pressure readings are color coded to indicate Normal 
blood pressure, mild, moderate, and severe hypertension.  BP readings will be automatically uploaded form the 
subject’s device to Way to Health.  If subjects have not completed their morning BP check by 11:00am they will 
receive a reminder via their chosen form of communication (email or text).  In the evening they will receive a 
reminder if they have not checked their BP by 9:00pm.  In addition to the standard feedback provided within the 
Withings app, subjects will receive automated feedback from the Way to Health platform on a weekly basis.  This 
message will contain the subject’s mean blood pressure over the preceding 7 days.  This message will also note 
whether the subject’s blood pressure is above or below a goal of <140/90 mm Hg and will report their compliance 
with scheduled BP checks.   
 
 
Social Incentive 
Patients will be randomly assigned (1:1) to either receive a social incentive or not. The social incentive will require 
the subject to identify a social supporter.  This individual can be a family member, friend, or other community 
member selected by the subject.  The social supporter will need to assent to the study and register on the Way to 
Health platform.  The social supporter will receive education on the importance of hypertension, how to measure 
blood pressure, and how to operate the Withings monitor.  If the social supporter is not present at the time of 
subject enrollment, they may assent to the study via telephone and/or by registering online at the Way to Health 
platform.  In this scenario they will receive education via telephone and/or online.    
 
The social supporter will choose whether they prefer to receive study communications via text message or email.  
The social supporter will receive a text or email message alert at 11:00am if the subject has not completed their 
morning BP reading and at 9:00pm if the subject has not completed their evening BP reading.  The social 
supporter will also receive feedback on the subject’s BP control from the Way to Health platform on a weekly 
basis.  This message will summarize the subject’s adherence to home monitoring in the preceding 7 days.  It will 
also contain the subject’s mean BP over the preceding 7 days and note whether the subject’s BP is above or 
below a goal of <!40/90 mm Hg.  The expectation is that the social support person will provide further feedback to 
the subject in order to improve both adherence and BP control 
 
Non-adherence 
BP readings will be automatically uploaded from the subject’s smartphone to the Way to Health platform.  If the 
subject goes 7 days without a single BP measurement, Way to Health will alert study personnel.  Study personnel 
will contact the subject by phone to remind them to check their BP and troubleshoot any potential technical 

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problems.  If the subject indicated that they do not wish to continue BP monitoring, study alerts will be 
discontinued and the study team will setup a time for the subject to return the BP device.  Even if the subject 
completely stops monitoring their BP, they will still remain in the study and be encouraged to complete the 30 and 
90-day follow-up assessments.  For analysis, if a subject completely stops BP monitoring, they will remain in the 
final analytic dataset but be considered “non-adherent” for the remaining study days (further details in section 8).    
 
 
7.2 48 Hour Follow-up Phone Call 
Enrolled subjects will be contacted at 48 hours +/- 24 hours after enrollment.  The purpose of this call will be to 
ensure the subject is able to properly use the device.  We will ask subjects if they have had any difficulty using the 
Withings blood pressure monitor or interacting with Way to Health.  If the patient is having difficulty using either 
system, troubleshooting will occur via the telephone.  If the issue cannot be resolved, the subject will be offered 
an additional in-person visit to trouble shoot the device and/or repeat device training.  The subject will also be 
screened for adverse events during this telephone call.   
 
7.3 30 Day Interview 
Enrolled subjects will be contacted at 30 days +/- 3 days after enrollment via electronic messaging (text message 
and/or email).  The subject will be asked to log into Way to Health and complete a short form.  This form will 
screen for adverse events and collect 30 day outcome data.  Blood pressure readings and adherence to twice 
daily blood pressure monitoring will be collected automatically via Way to Health and will not need to be assessed 
over the telephone.  Secondary outcomes assessed will include: 
 
 
TIA or stroke since enrollment 
 
Number of physician visits since enrollment (Primary care, cardiology, other) 
 
Number of emergency department visits since enrollment and reason for each visit 
 
Number of changes in antihypertensive medications since enrollment (dose adjustment and/or addition of 
a new agent) 
 
Patients perception of blood pressure monitoring device and study protocol ease of use (very difficult, 
moderately difficult, mildly difficult, easy to use) 
 
Patients perception of the utility of blood pressure monitoring (very useful, moderately useful, mildly useful, 
not useful) 
 
Patients perception of blood pressure control (adequately controlled, not adequately controlled) 
 
Subjects who do not complete the online form will be contacted by telephone in order to assess the same 
information.   
 
7.4 90 Day Follow-up Visit 
At 90 +/- 7 days from enrollment the subject will be seen for an in-person visit.  They will be asked to return the 
blood pressure monitor at that time and be screened for adverse events.  Outcomes will again be assessed.  
Blood pressure readings and adherence to twice daily blood pressure monitoring will be collected automatically 
via Way to Health and will not need to be assessed during this in-person visit.  Secondary outcomes assessed will 
include: 
 
 
TIA or stroke since 30 day phone call 
 
Number of physician visits since 30 day phone call (Primary care, cardiology, other) 
 
Number of emergency department visits since 30 day phone call and reason for each visit 
 
Number of changes in antihypertensive medications since 30 day phone call (dose adjustment and/or 
addition of a new agent) 
 
Patients perception of blood pressure monitoring device and study protocol ease of use (very difficult, 
moderately difficult, mildly difficult, easy to use) 

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 
Patients perception of the utility of blood pressure monitoring (very useful, moderately useful, mildly useful, 
not useful) 
 
Patients perception of blood pressure control (adequately controlled, not adequately controlled) 
 
Heart rate and blood pressure will be assessed in the non-dominate arm using an automated cuff.  This will be 
repeated 3 times and averaged to determine final blood pressure.  The modified Rankin Scale and NIHSS will 
also be assessed, as described in section 7.1.  Research personnel assessing both the mRS and the NIHSS will 
be trained and certified in its use.  Finally, for each subject we will tabulate the number of telephone calls to the 
study team initiated by the subject and the purpose of the call (blood pressure reading high/low, technical difficulty 
with device, other).       
7.5  Study Visits 
Subject visits will follow a standard visit schedule:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.  STATISTICAL ANALYSIS 
Demographics and past medical history variables will be summarized for all subjects using means or medians as 
appropriate for continuous variables and proportions for categorical variables.  We will compare the two study 
arms using Student’s t-test or Wilcoxon rank sum as appropriate for continuous variables and χ2 test for 
categorical variables.   
 
The primary outcome measure is adherence with blood pressure monitoring during the study period.  Adherence 
will be defined by dividing the number of successfully completed BP measurements (numerator) by the expected 
number of BP measurements (denominator).  The expected number of BP measurements is the number of days 
that the subject is in the study multiplied by 2.  Most subjects will be enrolled in the study for 90 days and will 
therefore be expected to check their BP 180 times.  Adherence in this case is the number of completed BP 
measurements divided by 180.  The 90-day follow-up visit has a window of +- 7 days, so for subjects that 
complete the study protocol the denominator will be adjusted accordingly.  Subjects whom withdrawal from the 
study and/or stop monitoring their BP before the 90-day follow-up visit will remain in the analysis. These subjects 
will be considered non-adherent for all BP measurements after they cease taking measurements and the 
denominator will be set at 180.  As an example, if a subject checks their BP 60 times in the first 75 days of the 
study and then ceases all BP measurements, adherence will be calculated as 60/180=33.3%.  After adherence 
has been calculated for all subjects we will evaluate the distribution of adherence for normality and compare 
adherence between the two study arms using Student’s t-test or Wilcoxon rank sum as appropriate.  A sample 
size of 90 will give us 80% power to detect a 30% difference between groups with α=0.05.   
 
 
 
Eligibility 
Confirmation & 
Enrollment 
48 +/- 
24 
Hours 
Day 30 
+/- 7 
Day 90 
+/-7 
Screening 
X 
 
 
 
Informed Consent 
X 
 
 
 
Eligibility [Inclusion 
& Exclusion 
C it
i ]
X 
 
 
 
Blood Pressure 
X 
 
 
X 
mRS 
X  
 
 
X 
NIHSS 
X 
 
 
X 
Outcomes 
X 
 
X 
X 
AE Screening 
 
X 
X 
X 

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Additional analysis will compare the change in blood pressure between the two groups.  The mean systolic and 
diastolic blood pressure in the first 7 days of the 90 day study period and the last 7 days of the 90 day study 
period will be calculated for each subject.  The average change in blood pressure will be compared between 
study arms using Student’s t-test or Wilcoxon rank sum as appropriate.  We will also compare the proportion of 
subjects with an average blood pressure <140/90 mm Hg in the final week of the study between groups using χ2.  
Subjects who drop out of the study or cease monitoring their BP prior to day 90 will be included in these analyses 
if they have a minimum of 14 days of monitoring.  For these subjects, we will utilize BP readings from the last 7 
days of monitoring.  The use of earlier readings carried forward should be conservative and bias the results 
toward the null.  Exclusion of subjects with less than 14 days of monitoring may truncate our sample and 
introduce bias, so we will conduct a sensitivity analysis in which we impute a change in BP for subjects with less 
than 14 days of monitoring of zero.   
 
We will compare secondary outcomes across study arms including number of calls to the study team, number of 
physician visits, number of emergency department visits, number of changes in antihypertensive medications, and 
the patient perception of: study protocol, utility of blood pressure monitoring, and blood pressure control.  We will 
also determine the relationship between adherence to blood pressure monitoring and change in blood pressure 
during the study period.  For this analysis, we will first determine the average adherence in the study population.  
We will compare the change in blood pressure in those with above average adherence to those with below 
average adherence.  This will be done in the full study population and then stratified by study arm.  In an 
exploratory analysis multivariable regression will be utilized to determine which factors were associated with a 
high level of adherence to the study protocol, defined as adherence above the study median.  We will investigate 
the following variables in a univariate analysis: age, sex, race, ethnicity, income, social support in the home, 
employment status, MMSE score, NIHSS, and modified Rankin Scale. Variables in the univariate analysis with 
p<0.10 will be incorporated into a multivariable logistic regression model.  We will test for an interaction between 
the social incentive and the variables in the multivariable model.   
 
9.  Data Handling and Record Keeping 
9.1  Confidentiality. 
 
 Paper-based records will be kept in a secure location and only be accessible to personnel involved in the 
study. 
 Computer-based files will only be made available to personnel involved in the study through the use of 
access privileges and passwords. 
 Prior to access to any study-related information, personnel will be required to sign statements agreeing to 
protect the security and confidentiality of identifiable information. 
 Whenever feasible, identifiers will be removed from study-related information.  
 

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 A Certificate of Confidentiality will be obtained, because the research could place the subject at risk of 
criminal or civil liability or cause damage to the subject’s financial standing, employability, or liability. 
 A waiver of documentation of consent is being requested, because the only link between the subject and 
the study would be the consent document and the primary risk is a breach of confidentiality.  (This is not an 
option for FDA-regulated research.)  
 Precautions are in place to ensure the data is secure by using passwords and encryption, because the 
research involves web-based surveys.   
 Audio and/or video recordings will be transcribed and then destroyed to eliminate audible identification of 
subjects.  
 Other (specify):    
 
 
9.2  Source Documents 
Source documents are all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial.  Source data are contained in source 
documents   Examples of these original documents, and data records include: hospital records, clinical and office 
charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, 
recorded data from automated instruments, copies or transcriptions certified after verification as being accurate 
and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and 
records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in this research.   
 
Trained members of the research team may review source documents at the time of enrollment/consent in order 
to ensure patient eligibility.  Necessary data from the source documents will be recorded on the case report form.  
Copies of source documents will not be needed for this study.   
9.3 Case Report Forms 
The study case report form (CRF) is the primary data collection instrument for the study.  Hard copy of all case 
report forms will be kept secure in a locked cabinet accessible to the study primary investigator and study 
coordinator.  Data for this study will also be stored in an electronic database via the Way to Health platform.  Way 
to Health is secure and HIPAA compliant.  Data contained within Way to Health will only be accessible to 
appropriately trained study personnel.  
9.4 Records Retention 
It is the investigator’s responsibility to retain study essential documents for at least 2 years after the last approval 
of a marketing application in their country and until there are no pending or contemplated marketing applications 
in their country or at least 2 years have elapsed since the formal discontinuation of clinical development of the 
investigational product.   
 
We will retain all case report forms and the electronic databases for a minimum of two years after completion of 
the study.   
 
Personal identifiers will not be released to other investigators under any circumstances.  If at any time the data is 
to be shared with other investigators for future research, it will be de-identified prior to release.  The data collected 
in this study will not become a part of the subject’s permanent record.  
9.5  Subject Privacy/Protected Health Information 
The following protected health information (PHI) will be collected: 
 
Name 
 
Address 
 
Social Security Number 

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 
Medical record number 
 
Phone number 
 
Email address 
 
Medical history 
 
Current and past medications or therapies 
 
Information from a physical examination that generally also includes blood pressure reading, 
heart rate, breathing rate and temperature 
 
Information from laboratory and imaging tests such as echocardiograms, MRI and CT scans.   
 
Collected PHI will be recorded on the case report form, which will be secured as detailed above. It will otherwise not 
be disclosed to anyone outside of key study personnel.   
 
The HIPPA authorization for this study will be incorporated into the informed consent form.  In the event that a subject 
revokes authorization to collect or use PHI, the investigator, by regulation, retains the ability to use all information 
collected prior to the revocation of subject authorization.  For subjects that have revoked authorization to collect or 
use PHI, attempts will be made to obtain permission to collect at least vital status (i.e. that the subject is alive) at the 
end of their scheduled study period.   
9.6  Tissue Specimens 
Not applicable 
9.7  Genetic Testing 
Not applicable 
 
10.  RISK/BENEFIT ASSESSMENT 
10.1  Potential Study Risks 
There are no risks associated with the blood pressure monitor used in this study.  The study team will take every 
possible step to maintain your privacy, including using password protected files and minimizing the use of 
identifying information on study documentation, but whenever private health information is collected there is 
always a small risk that a breach of confidentiality could occur.  
10.2  Potential Study Benefits 
This study has the potential to benefit all subjects.  Hypertension is the most important modifiable risk factor for 
stroke and an important risk factor for myocardial infarction, chronic kidney disease, and other serious medical 
conditions.  Study education about the importance of hypertension, goal blood pressure levels, and regular 
monitoring of blood pressure may lead to improved blood pressure control in subjects, which in turn has the 
potential to lower the risk of serious medical conditions, including heart attack and stroke.  There is also a 
potential societal benefit, as this study will provide important insights into adherence with home monitoring in 
patients with cerebrovascular disease and may be useful for future larger studies which combine home monitoring 
with therapeutic interventions to lower blood pressure with the goal of reducing the risk of future stroke.  
10.3  Alternatives to Participation 
Participation in this research study is voluntary.  Subjects may choose not to participate; their decision to 
participate or not will not affect their regular medical care in any way.   
10.4  Risk/Benefit Assessment 
Considering the minimal risk to participants and the potential benefit both to individual participants and to society, 
the risk to benefit ratio is favorable.   
 

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11.  Data and Safety Monitoring 
 
This study will be monitored by: 
 
 Principal Investigator 
 Sponsor or contract research organization 
 NCI sponsored cooperative group 
 Cancer Center (if mandated by CTSMRC) 
 Medical monitor 
 Safety monitoring committee 
 Data and safety monitoring board 
11.1  Definitions 
      Adverse Event 
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity 
during the course of the study.  Intercurrent illnesses or injuries should be regarded as adverse events.  
Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality: 
 
Results in study withdrawal 
 
Is associated with a serious adverse event 
 
Is associated with clinical signs or symptoms 
 
Leads to additional treatment or to further diagnostic tests 
 
Is considered by the investigator to be of clinical significance 
Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious adverse event is any AE that is:  
 
Fatal 
 
Life-threatening 
 
Requires or prolongs hospital stay 
 
Results in persistent or significant disability or incapacity 
 
A congenital anomaly or birth defect 
 
An important medical event 
 
Important medical events are those that may not be immediately life threatening, but are clearly of major 
clinical significance.   They may jeopardize the subject, and may require intervention to prevent one of the 
other serious outcomes noted above.  For example, drug overdose or abuse, a seizure that did not result in 
in-patient hospitalization or intensive treatment of bronchospasm in an emergency department would 
typically be considered serious.  
 
All adverse events that do not meet any of the serious criteria will be regarded as non-serious adverse 
events.  
Adverse Event Reporting Period 
The study period during which adverse events must be reported is defined as the period from the initiation of 
any study procedures to the end of the study treatment follow-up.  For this study, the study treatment follow-
up is defined as 90 days from enrollment, or at the final study visit, whichever comes first.  
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition should be 
recorded as an adverse event if the frequency, intensity, or the character of the condition worsens during 
the study period. 
General Physical Examination Findings 

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At screening, any clinically significant abnormality should be recorded as a preexisting condition.  At the end 
of the study, any new clinically significant findings/abnormalities that meet the definition of an adverse event 
will be recorded and documented as an adverse event.  
Post-study Adverse Event 
All unresolved adverse events will be followed by the investigator until the events are resolved, the subject 
is lost to follow-up, or the adverse event is otherwise explained.  At the last scheduled visit, the investigator 
should instruct each subject to report any subsequent event(s) that the subject, or the subject’s personal 
physician, believes might reasonably be related to participation in this study.  The investigator should notify 
the FDA and IRB of any death or adverse event occurring at any time after a subject has discontinued or 
terminated study participation that may reasonably be related to this study.  
Hospitalization, Prolonged Hospitalization or Surgery 
Any adverse event that results in hospitalization or prolonged hospitalization will be documented and 
reported as a serious adverse event unless specifically instructed otherwise in this protocol.  Any condition 
responsible for surgery will be documented as an adverse event if the condition meets the criteria for an 
adverse event.  
 
Neither the condition, hospitalization, prolonged hospitalization, nor surgery are reported as an adverse 
event in the following circumstances: 
 
Hospitalization or prolonged hospitalization for diagnostic or elective surgical procedures for a 
preexisting condition.  Surgery should not be reported as an outcome of an adverse event if the 
purpose of the surgery was elective or diagnostic and the outcome was uneventful. 
 
Hospitalization or prolonged hospitalization required to allow efficacy measurement for the study. 
 
Hospitalization or prolonged hospitalization for therapy of the target disease of the study, unless it is 
a worsening or increase in frequency of hospital admissions as judged by the clinical investigator. 
11.2 Recording of Adverse Events 
At each contact with the subject, study personnel will seek information on adverse events by specific questioning 
and, as appropriate, by examination. Information on all adverse events will be recorded immediately in the source 
document, and in the appropriate adverse event module of the case report form (CRF).  All clearly related signs, 
symptoms, and abnormal diagnostic procedures with their results will be recorded in the source document, 
grouped under one diagnosis. 
 
All adverse events occurring during the study period will be recorded.  The clinical course of each event should be 
followed until resolution, stabilization, or until it has been determined that the study treatment or participation is 
not the cause.  Serious adverse events that are still ongoing at the end of the study period must be followed up to 
determine the final outcome.  Any serious adverse event that occurs after the study period and is considered to 
be possibly related to the study treatment or study participation should be recorded and reported immediately. 
11.3  Reporting of Serious Adverse Events 
Reports of all serious adverse events (including follow-up information) must be submitted to the IRB promptly. All 
serious adverse events, regardless of relatedness or expectedness to the study drug, will be submitted via 
PennAEs.  Copies of each report and documentation of IRB notification and receipt will be kept in the Clinical 
Investigator’s binder. 
11.4  Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of this study.  Safety monitoring will 
include careful assessment and appropriate reporting of adverse events as noted above.  There will not be an 
internal or independent data and safety monitoring board.   
 

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12. AUDITING, INSPECTING 
12.1  Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, government regulatory 
bodies, and University compliance and quality assurance groups of all study related documents (e.g. source 
documents, regulatory documents, data collection instruments, study data etc.).  The investigator will ensure the 
capability for inspections of applicable study-related facilities.  Participation as an investigator in this study implies 
acceptance of potential inspection by government regulatory authorities and applicable University compliance and 
quality assurance offices. 
 
13.  SUBJECT COMPENSATION 
Subjects will be compensated $50 in the form of a Greenphire ClinCard.  Compensation will cover the subjects 
transportation costs to/from study visits and their time for participation in study visits.  The ClinCard is a prepaid 
card which the subject can use for in-store or online purchases similar to a credit or debit card.  It can also be 
used at an ATM or bank to receive cash.  The  will be given to the subject upon completion of all study visits and 
after they have returned the Withings Blood Pressure monitor to the study team.   
 
 
14.  RESOURCES NECESSARY FOR HUMAN RESEARCH PROTECTION 
This research protocol will be conducted by the clinical research section of the stroke division of the department of 
neurology.  The research team consists of three full time clinical research coordinators, one nurse practitioner, 
three vascular neurology fellows, and five vascular neurology attendings.  All members of the research team will 
be required to have Patient Oriented Research training through the University of Pennsylvania Knowledge Link 
training system.  All members of the research team who will be assessing NIHSS and mRS will be trained in the 
administration of these scales using web-based training systems.  The research team will maintain training 
records, including copies of all pertinent certificates.    
 
Prior to initiation of the study, the research team will have an in-service session to review the study protocol and 
procedures in detail.  While the study is underway, the research team will meet weekly to discuss the study, 
including enrollment, follow-up, and any other issues which may arise.   
 
15.  STUDY FINANCES 
15.1  Funding Source 
Funding for this study will be provided by an internal pilot grant awarded from the Penn Medicine Center for 
Health Care Innovation as well as an internal pilot grant awarded from the University of Pennsylvania Department 
of Neurology Robbins Fund.  
 
15.2  Budget 
 
  
Cost/Unit 
Number of Units 
Total Cost 
Blood Pressure Monitors 
$ 130 
30 
$ 3,900 
Way to Health Platform Development 
$18,000 
1 
$ 18,000 
Way to Health Monthly Costs 
$500 
15 
$7,500 
Way to Health 2-way messaging 
$1,250 
1 
$1,250 
PI Salary 
$25,601 
1 
$25,601 
Research Coordinator 
$8,435 
1 
$8,435 

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Miscellaneous Office Supplies 
$200 
1 
$200 
Greenphire ClinCards 
$50 
90 
$4,500 
 
 
Total Cost: 
$69,386.00 
 
 
 
 
15.3 Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain greater 
than the minimum allowable by their institution, etc.) must have the conflict reviewed by a properly constituted 
Conflict of Interest Committee with a Committee-sanctioned conflict management plan that has been reviewed 
and approved by the study sponsor prior to participation in this study.  All University of Pennsylvania investigators 
will follow the University conflict of interest policy.   
 
16.  PUBLICATION PLAN 
Dr. Mullen, the principal investigator for this protocol, is responsible for publishing the results of this study.  
Neither the complete nor any part of the results of the study carried out under this protocol will be published or 
passed on to any third party without the consent of the principal investigator.  Any investigator involved with this 
study is obligated to provide the principal investigator with complete test results and all data derived from the 
study.   
 
17. REFERENCES 
 
1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, et al.  Heart Disease and Stroke 
Statistics—2013 update: a report from the American Heart Association. Circulation. 2013 January 1;127(1):e6-
e245.   
 
2. Ovbiagele B, Goldstein LB, Higashida RT, Howard VJ, Johnston SC, Khavijou OA. Forecasting the future of 
stroke in the United States: A policy statement from the American Heart Association/American Stroke 
Association.  Stroke. 2013 Aug;44(8):2361-75. 
 
3. O'Donnell MJ, Xavier D, Liu L, Zhang H, Chin SL, Rao-Melacini P, et al. Risk factors for ischaemic and 
intracerebral haemorrhagic stroke in 22 countries (the interstroke study): A case-control study. Lancet. 
2010;376:112-123. 
 
4. Saposnik G, Goodman SG, Leiter LA, Yan RT, Fitchett DH, Bayer NH, et al. Do patients with sroke, coronary 
artery disease, or both achieve similar treatment goals. Stroke. 2009, 40:1417-1424.   
 
5. Law MR, Morris JK, Wald NJ.  Use of blood pressure lowering drugs in the prevention of cardiovascular 
disease: Meta-analysis of 147 randomised trials in the context of expectations from prospective 
epidemiological studies. British Medical Journal. 2009;338. 
 
6. Progress Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen 
among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet. 2001;358:1033-1041 
 
7. Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B, et al.  Use of ramipril in preventing stroke: 
Double blind randomised trial. British Medical Journal. 2002;324:699 

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8. Turan TN, Nizam A, Lynn MJ, Montgomery JL, Derdeyn CP, Fiorella D, et al.  Relationship between risk factor 
control and vascular events in the stenting and aggressive medical management for preventing recurrent 
stroke in intracranial stenoiss trial. International Stroke Conference 2014 (Abstract).  
 
9. Osterberg L, Blaschke T. Adherence to medication. New England Journal of Medicine. 2005;353:487-497. 
 
10. Siegel D. Barriers to and strategies fpr effective blood pressure control. Vasc Health Risk Manag. Mar 
2005;1(1):9-14. 
 
11. Kerry SM, Markus HS, Khong TK, Cloud GC, Tulloch J, Coster D, Iet al.  Home blood pressure monitoring 
with nurse-led telephone support among patients with hypertension and a history of stroke: A community-
based randomized controlled trial. CMAJ. 2013;185:23-31