A Novel Disease Management Platform Delivered Via Smartphone Application for the Management of Patients With Heart Failure: Pilot Study
Phase: NA
Conditions: Heart Failure
Sponsor: Massachusetts General Hospital

COVER PAGE 
 
Protocol title: Disease Management Platform for Heart Failure 
(DMP-HF) 
 
NCT number: NCT04782973 
 
Document date: 06/17/2021 
 
 
 

PRINCIPAL/OVERALL INVESTIGATOR 
Pradeep Natarajan, MD 
 
PROTOCOL TITLE 
A novel disease management platform delivered via smartphone application for the 
management of patients with heart failure: pilot study 
 
FUNDING 
AstraZeneca  
 
VERSION DATE 
6/17/2021 
 
I. 
SPECIFIC AIMS  
 
Specific Aim 1: To test the feasibility of implementing the AMAZE™ disease management 
platform intervention after in-patient heart failure hospitalization and patient perceived value of 
the AMAZE™ disease management platform.  
Specific Aim 2: [Exploratory] To test whether a digital health platform leads to heart failure 
symptom changes using the Kansas City Cardiomyopathy Questionnaire (KCCQ), patient daily 
log compliance, patient app usage, patient app messaging, changes in hospital readmissions and 
use of ancillary healthcare resources.  
 
 
II. 
BACKGROUND AND SIGNIFICANCE   
 
Public Health Significance  
 
Heart failure (HF) management and readmissions remain at the top of the list of complex topics in 
cardiovascular medicine, in the United States. The CDC estimates 6.5 million adults in the United States 
have heart failure and costs in 2012 were approximately 30.7 billion dollars {Benjamin, 2019 #472}. This 
conversation spans across multiple sectors in our complex healthcare system; involving doctors, 
administrators, payors, patients and caretakers.  
Current system-wide programs to curb HF-related hospital readmissions have shown inconsistent results. 
However, outpatient transitional care supportive programs have been linked to improved HF-related 
outcomes, including reduced hospital readmissions, in small studies. Small studies also indicate that 
remote transfer of non-invasive data through telemonitoring (e.g., blood pressure and weight) and 
structured telephone support may reduce hospital readmissions in a cost-effective manner. Advances in 
technologies, such as electronic health records (EHRs), smartphones {Chow, 2015 #475; Neubeck, 2015 
#474; Hamilton, 2018 #473}, and wearable sensors {Martin, 2015 #479; McConnell, 2017 #478; Guo, 
2019 #477; Perez, 2019 #476} may have prognostic implications beyond the conventional in-office 
clinical assessment. However, prior studies leveraging these technologies have focused on either (1) 
prognosis, which is often not transferable across health systems, or (2) automated risk reduction, which 
delivers simple therapies at scale with few personalized factors.  
 

Current digital health endeavors have not had major successes yet for reasons including: (1) risk-averse 
investments; (2) key problems unaddressed, (3) lack of synergy between companies and healthcare; (4) 
misaligned financial incentives across patients, providers, payers, and companies; (5) the change-averse 
cultures and complex internal relationships of healthcare systems; (6) data interoperability that requires a 
long development cycle; and (7) healthcare distribution that is currently enterprise-facing and not 
consumer-aligned.  
 
The present pandemic has placed significant strains on the link between clinicians and patients 
highlighting the need for rapid innovation for virtual care.  
 
The primary goals of the present proposal are to demonstrate feasibility of this novel platform, to assess if 
the DMP can be feasibly implemented prior to hospital discharge for patients hospitalized for heart 
failure. This is a first necessary step before testing efficacy in a large multi-center study. 
 
Description of AstraZeneca Platform 
 
AstraZeneca has proposed a Disease Management Platform (DMP) to be used across multiple disease 
indications to provide a unified experience for the management of patients throughout their patient care 
journey. This DMP will integrate multiple systems, including a patient App where patients can enter 
mood, symptoms, weight measures, vital signs such as blood pressure (BP) and medication adherence.  
This input will feed directly to a clinician dashboard that will allow the clinical care team access to a real-
time view of the patient’s state both in and out of the clinic. An evidence generation study in patients with 
Heart Failure (HF) can be used to assess the implementation of the DMP in patients with HF discharged 
from the hospital.  
 
AstraZeneca suggests the platform proposes to transform cardiovascular medicine by: (1) focusing on 
transformative development instead of just testing off-the-shelf solutions; (2) working with complex 
patients and data at an academic medical center who is invested in healthcare transformation; (3) 
amassing a diverse team of experts in cardiovascular medicine, investigation, engineering, and strategy; 
(4) focusing on the specific issue of HF, where current healthcare system strains are non-viable for 
patients, providers, and payers; and (5) improving the healthcare experience for both patients and 
healthcare professionals. 
 
Patient Smartphone App  
The disease management platform (DMP) was co-developed by AstraZeneca (research & development 
center), Gaithersburg, Maryland, USA and BrightInsight, Inc., a Silicon Valley, CA-based health care 
technology company. AstraZeneca aims to improve patient engagement in their health, and enable 
convenient, effective support by allowing for messaging between study staff and patients based on a 
patient’s progress with their care plan. The DMP consists of a patient held smartphone App, a clinician 
dashboard and a suite of clinical programs embedded into EPIC electronic medical record with 
configurable rules. The DMP App allows enrolled patients with heart failure to record relevant symptoms, 
biometrics, and medication adherence, as well as access their personal health information and stay 
connected with their care team. Patient-provided input via the daily log and monthly surveys are available 
for the healthcare team to view and assess. Patients can also access curated education links, view 
upcoming appointments, review trends in their recorded data, and send messages to the care team.  The 
DMP App was developed by means of user-experience and design elements to ensure ease of use for all 
participants. The registration process is streamlined and will only take a few minutes to set up. In addition 

to requiring a password-secured account for the DMP App, patients will be encouraged to add a passcode 
to their mobile device for additional security during the study.   
 
 
AstraZeneca Content Procurement for in App Education Feature 
AstraZeneca considers the Smartphone App as “patient-support” and not ‘commercial’ use. All of the HF 
App education links are trusted and reputable third-party medical sources. See below for a list of sources; 
all referenced sources are cited in the references section for web content that appears in the patient 
smartphone App. All content has been reviewed by AstraZeneca and MGH clinical teams with a 
proficiency in health literacy and patient education guidelines. 
Referenced sources include:  
▪ 
American Heart Association (www.heart.org) 
▪ 
American College of Cardiology (www.cardiosmart.org) 
▪ 
Heart Failure Society of America (www.hfsa.org) 
 
Study staff and participants will have tech support via email (amaze.support@brightinsight.com) tech 
support provided by BrightInsight, Inc. In addition to this participant support, additional support is 
provided to study staff by two identified IT professionals from LexTech.  
 
Provider Dashboard  
The clinician dashboard is also produced by BrightInsight, Inc to work in conjunction with the DMP App 
for patients. AstraZeneca aims to strengthen existing clinical resources and reduce the burden and time 
spent on patient preparation and follow-ups by surfacing real-time insights to clinical teams and providing 
the tools to support patients easily and efficiently. The dashboard features secure, 2-way messaging to 
individuals and groups of patients, enabling efficient follow-up to answer patients’ questions and outreach 
to encourage engagement with the disease management platform. Clinicians can also reach out to patients 
through multi-channel communication methods, including email linked to Patient Gateway and a text chat 
feature in the App, to promote engagement and responses to surveys. The clinical team is alerted based on 
patients' survey responses and engagement patterns, allowing them to identify risks, intervene early 
through supportive messaging, and reduce post-admission recovery complications. In summary the goals 
here is to provide, the real-time information about patients’ health status, combined with secure easy 
messaging with patients, which will enable an efficient, effective workflow for clinical teams to support 
patients through recovery and health maintenance.  
 
III. 
RESEARCH DESIGN AND METHODS 
Sample size: 70 post hospital admission at Massachusetts General Hospital (MGH), general cardiology 
with a diagnosis of heart failure with reduced ejection fraction (HFrEF), heart failure with moderate 
ejection fraction (HFmEF), or heart failure with preserved ejection fraction (HFpEF). Patients will be 
identified via an automated computer-based algorithm using information retrieved from electronic health 
records {Protocol #: 2020P002432}. 

 
 Inclusion/Exclusion Criteria for intervention study population 
• 
Intervention study population: Patients 21 years and older with a diagnosis of heart failure 
[HFrEF(<40%), HFmEF(40-49%) HFpEF(≥50%)] admitted to MGH cardiology services (Ellison 
10 and 11). Patients must have access to smartphone and email, be English speaking/reading and 
discharged home.  
 
Non-recruited EHR-based control populations for the exploratory objectives for this single-arm 
interventional pilot: 
 
• 
Historical MGH control population: Patients 21 years and older with a diagnosis of HF admitted 
to MGH cardiology services (Ellison 10 and 11) admitted in the year prior discharged home. 
Matched 1:2 based on age, sex, HFrEF(<40%), HFmEF(40-49%) HFpEF(≥50%), CAD, T2D, 
month admitted (minus 1y), number of prior 12mo hospital admissions. 
 
• 
Contemporaneous BWH control population: Patients 21 years and older with a diagnosis of HF 
admitted to BWH cardiology services admitted during intervention study population enrollment 
and discharged home. Matched 1:2 based on age, sex, HFrEF(<40%), HFmEF(40-49%) 
HFpEF(≥50%), CAD, T2D, month admitted, number of prior 12mo hospital admissions. 
 
• 
Historical BWH control population: Patients 21 years and older with a diagnosis of HF admitted 
to BWH cardiology services admitted in the year prior discharged home. Matched 1:2 based on 
age, sex, HFrEF(<40%), HFmEF(40-49%) HFpEF(≥50%), CAD, T2D, month admitted (minus 
1y), number of prior 12mo hospital admissions. 
 
Inclusion Criteria 
● Adults (>21 years) admitted to MGH Cardiology services (Ellison 10 and 11) with a diagnosis of 
acute or chronic heart failure [HFrEF(<40%), HFmEF(40-49%) HFpEF(≥50%)] (or to BWH 
Cardiology services for BWH EHR-based controls) 
● Has a smartphone or iPad and is willing to enter health metrics into DMP App and email willing 
to use for the study 
● Access to the internet 
● Established or with plan to establish primary cardiologist at MGH (or at BWH for BWH EHR-
based controls) 
● Discharged home or to self-care (with or without home services) 
 
Exclusion Criteria  
• 
Moderate or severe cognitive impairment 
• 
Non-English-speaking 
• 
Palliative management only (comfort measures)  
• 
Does not own a smartphone or iPad (not considered for EHR-based controls) 
• 
Incarcerated 
• 
Enrolled in study with similar outcomes 
 

Study Outcomes 
 
Primary: To test the feasibility of implementing the AMAZE™ disease management platform 
intervention after in-patient heart failure hospitalization and patient perceived value of the AMAZE™ 
disease management platform. The feasibility will be measured using conversion rate (percent of patients 
approached who enroll on the disease management platform). The perceived value will be measured using 
the participants mHealth App Usability Questionnaire (MAUQ) score. 
  
Exploratory: The following exploratory outcomes will be measured as follows: 
 
1. Heart failure symptom changes using the Kansas City Cardiomyopathy Questionnaire (KCCQ). 
a. Heart failure symptoms will be measured as the changes in KCCQ scores between the 30 
day and 60 day time-points. 
 
2. Patient daily log compliance. 
a. Daily log compliance will be measured after 60 days using the total number of days 
patient completes daily log in the AMAZE™ app out of total days patient is enrolled in 
the app. 
 
3. Patient app usage. 
a. Patient app usage will be measured as the number of days the patient engages (i.e. 
completes daily log, sends a message) with the app at least once a day during the study 
period. 
 
4. Patient app messaging. 
a. Patient app messaging will be measured as the number of messages sent by the patient 
during the 60 day study period. 
 
5. Changes in hospital readmissions. 
a. Hospital readmission rates in the enrolled study group will be compared to readmission 
rates in historical control groups. 
 
6. Use of ancillary healthcare resources. 
a. Rates ancillary healthcare resources (i.e. emergency room visits, urgent care visits, 
unexpected ambulatory care visits, cardiac rehab) in the enrolled study group will be 
compared to rates of usage in a historical control group. 
 
Subject Enrollment  
 
Overview 
Approximately 70 patients will be enrolled in the study. Patients admitted to MGH cardiology will be 
screened by study staff for inclusion/exclusion criteria. Study staff will obtain approval to approach 
eligible patients by the inpatient clinical team. Approximately 2-days prior to discharge, suitable patients 
will be consented and onboarded with study staff, with the technical support available 24/7 via email or 
phone through BrightInsight, Inc.  

 
 
Procedure for obtaining informed consent 
 
We will use Mass General Brigham electronic resources to identify and screen patients for the eligibility 
criteria listed above. Our internal (MGH) data and analytics team developed an automated process to 
screen and extract a list of eligible admitted patients on Ellison 10/11 through Research Patient Data 
Registry (RDPR) and Enterprise Data Warehouse (EDW) (IRB Protocol # 2020P002432). The list will be 
sent to the study staff daily; study staff will perform chart review of participants on the list to confirm 
eligibility.  
 
We will focus on patients with a diagnosis of heart failure, who speak and read English.  
 
We will also use the attached study flyer to advertise the study to patients on inpatient floors, with nurse 
manager approval for the respective floors.  
 
We will create a database of potentially eligible subjects and contact their nurses to confirm eligibility and 
that they are suitable for the study. We will also verify that the nurse approves of a coordinator 
approaching their patient. A study coordinator will approach approved and eligible patients to introduce 
the study. The study coordinator will then review the consent form and study procedure and obtain 
written consent from the patient. Study coordinators will use an iPad to go over the consent form with the 
patient. The subject and the study coordinator will sign electronic copies of the consent form using Adobe 
eSign. Adobe and the iPad will be used whenever possible, but subjects also may be consented with a 
paper consent form.  Subjects will be sent a copy of the consent form via email from Adobe, which 
automatically sends a pdf copy of the signed consent form to all parties, or they will be sent a scanned 
paper copy via the Partners send secure system. Subjects with any cognitive disability that prevents them 
from consenting for themselves will also prevent them from using the AMAZE application. Therefore, 
subjects who cannot consent for themselves will be excluded from the study. Staff will clearly explain 
that participation in the study is voluntary and the subject can choose to withdraw from the study at any 
time.  
 
We will approach patients who are interested in joining the study but are transferred to other inpatient 
units for various reasons (procedures etc.) at their new location if permitted by their care team. We will 
verify that the patient is still interested in joining the study before consenting and onboarding them. 
 
If we are unable to consent and/or onboard patients to the study while they are in the hospital, we will 
schedule a time to do so remotely using Partners Healthcare Enterprise Zoom once they have been 
discharged. In such cases, we will aim to enroll the patient within three days of being discharged from the 
hospital. With their consent, we will mail them their study devices: a blood pressure cuff and home scale. 
Patients can also refuse the study when talking to the research coordinator. 
 
For enrolled subjects, we will send an email explaining the study to the subjects’ outpatient cardiologist 
with information on how they can view the provider dashboard within EPIC. The demographics (age, sex, 
race/ethnicity) of those screened for our study will be collected for recruitment analyses. We will retain 
identifiers of screened subjects in our pre-screening log to ensure accurate recruitment of subjects and 
assist with algorithm development, since the algorithm developed under protocol 2020P002432 will be 
assessed and revised for accuracy during this study. Once the identifiable pre-screening log information is 
no longer needed in this study it will be stripped of all identifiers and we will only retain age, sex, and 
race/ethnicity  
 
  

 
Onboarding with AMAZE application 
STEP 1: Download AMAZE 
• 
On a smartphone or iPad, patients go to IOS or Android App store and search for the AMAZE App. 
• 
Install the AMAZE app on their smartphone or iPad.  
STEP 2: Sign Up  
• 
Open App – select Create an account.  
• 
Review welcome screen with introduction to the App click Next. 
• 
Pop-up appears regarding Invitation Code for the App – to be sent in email provided. Select 
Okay to continue.  
• 
Enter your email address you would like to link to the App. Select Continue. 
• 
Type in the [PMRN] and the Invitation code to sign up for an account (provided by study staff).  
• 
Create a password and confirm password. Select checkbox next to “I have read and accept the 
Terms & Conditions and Privacy Policy.”   
o AstraZeneca and Bright Insight will disclaim the Patient App Terms of Use and the 
AMAZE Privacy Policy, so they will not apply to a user of the app who is enrolled in this 
research study for purposes of the research. 
• 
Add phone number (required) 
• 
Select Get Started. 
o The patients will be asked daily if they took medications prescribed for Heart Failure, as 
part of the daily log. The list will integrate from EPIC; patients are not able to edit the 
medication list through the phone App.  
o They’ll be prompted to accept push notifications from the App. Patients say 
“Yes/Accept/OK” to allow notifications for medication reminders, messages from the 
clinical team, and updates to instructions. These notifications will appear on the 
lock/home screen of the mobile device. They will never contain personal health 
information; they will simply prompt patients to open App for a new task, message, or 
instruction. 
Devices 
A blood pressure cuff and scale will be provided to all participants, along with instructions on how to use 
them. 
Study Procedures 
Study Staff and Nurse Navigator Role 
A nurse navigator, with experience working with patients and cardiologists on cardiovascular disease 
prevention, management, and rehabilitation will also work with patients through the dashboard to 
promote adherence to care plans and provide support and encouragement throughout preparation and 
recovery. The nurse navigator will partner with research staff and the cardiology care team to ensure a 
seamless support system for patients. The nurse is a MGH staff who is a trained in coaching, patient 

support, engagement, and encouragement. The nurse navigator builds a supportive, mentor-like 
partnership with the patient, fosters encouragement, goal setting and accountability to maximize 
engagement. The nurse sends encouraging messages and addresses patients’ non-clinical and clinical 
needs, when possible. The nurse promotes and assists patients with adherence to completing the tasks in 
their DMP App including engagement in heart failure-related education, completing a daily log, monthly 
surveys and care team communication. 
 
The nurse navigator partners with patients and the clinical team via the DMP dashboard messaging 
system. The nurse navigator facilitates triage of clinical needs and will act as a liaison between patients 
and the care team to bridge the gap and improve patient navigation, familiarity and stability in a complex 
medical system. Outgoing telephone calls to patients will be documented in EPIC as a Telephone 
Encounter, calls will be routed to a study physician for review and to clinical physicians when 
longitudinal care questions or follow-up may be indicated.  The nurse operates under the supervision of 
MGH cardiology team of licensed physicians and nurse practitioners, and all patient communication 
adheres to structured protocols and guidelines set forth by MGH clinical leadership. 
 
Clinical providers will be able to monitor the subjects’ App entries within EPIC via the provider 
dashboard. Study staff will be able to access the Provider dashboard, the clinician messaging function will 
be used for study communications and clinical care team communications for Heart Failure; any clinical 
questions needing MD or NP expertise will be directed to the patient's cardiology team by the nurse 
navigator for review and feedback.  
Messaging – patient → clinical care team → patient 
1. The patient can only communicate to the clinical care team by writing and sending a message via 
the DMP HF App. 
2. The patient can receive communication from the clinician care team by opening the HF app and 
reading any newly received messages. 
3. The care team can only read and write messages back to the patient in the care team portal via the 
“Messages” tab. The care team cannot create a Telehealth interaction or similar from the portal. 
Only written messages are allowed. 
4. In terms of UX, the Messaging feature for the patient functions very similar to MGB Patient 
Gateway but is not integrated into its in-basket feature. 
5. For example, if the patient has a question, the patient will send a message to clinical care team 
from the App. The patient must wait for a message response. There’s no “real-time” 
communication or chat feature.  
6. A care team member won’t instantly respond unless they happen to be in the portal, see the 
message, and respond directly 
 
Clinical staff will be alerted within the provider dashboard when the following parameters are met, as 
patients enter information into their “daily log” within the HF DMP App.:  
Metric 
Value with unit 
Duration 

Medication Compliance 
<75% 
Over 7 days 
Systolic increase 
 20 mmHg 
Within 3 days 
Systolic decrease 
 20 mmHg 
Within 3 days 
Diastolic increase 
 10 mmHg 
Within 3 days 
Diastolic decrease 
 10 mmHg 
Within 3 days 
Systolic greater than 
150 mmHg 
once 
Systolic less than 
100 mmHg 
once 
Diastolic greater than 
90 mmHg 
once 
Diastolic less than 
60 mmHg 
once 
Weight gain 
3lbs or 6lbs 
Within 2days or 7 days 
Weight loss 
6lbs 
Within 7 days 
# of New Symptoms 
1 new symptom since previous log 
once 
New Shortness of Breath 
At least 1 entry 
Within 7 days 
New Leg Swelling 
At least 2 entries 
Within 7 days 
New Difficulty Sleeping Flat 
At least 1 entry 
Within 7 days 
New fatigue 
At least 3 entries 
Within 7 days 
New loss of appetite 
At least 3 entries 
Within 7 days 
New Difficulty Concentrating 
At least 3 entries 
Within 7 days 
New cough 
At least 3 entries 
Within 7 days 
New weakness 
At least 3 entries 
Within 7 days 
New Dizziness 
At least 3 entries 
Within 7 days 
Activity 
< 5 minutes total activity reported 
Within 14 days 
KCCQ score decrease 
At least 25 points 
Since previous KCCQ on file 
Mood (Bad only) 
At least 7 entries 
Within 14 days 
Heart Rate greater than 
>100 bpm 
once 
Heart Rate less than 
<60 bpm 
once 
Log Compliance 
< 1 entry 
Over 5 days 
 
Participants will be asked and encouraged to enter information into the App daily. Information that will 
be entered into the App include: 
 
• 
Physical well-being – How are you feeling today? [bad, okay, good] 
• 
Medications – Have you taken all of your medications for heart failure today? [yes, no] 
o Medication list will be auto populated in the DMP App as part of the EPIC integration 
process. The list the patient can see in the HF DMP App will mimic what is in Patient 
Gateway. 
• 
Symptoms – What symptoms do you have today? [cough, difficulty sleeping flat, dizziness, 
fatigue, leg/ankle/foot swelling, loss of appetite, shortness of breath, weakness, none of these] 
• 
Activity – How active were you today? [Mild - none or <5 minutes, Moderate – 6 to >30minutes] 
• 
Biometrics – weight, blood pressure, heart rate 
• 
Kansas City Cardiomyopathy Questionnaire (see attachment) at 30-and 60-days 
 
Participants without access to a home scale and/or blood pressure monitor to measure weight and blood 
pressure will be provided with device(s) purchased by the research study fund. Participants receiving a 
device will be able to keep the device(s) once the study has ended.  

Participant Education Objectives and Outline 
The educational components of this pilot study aim to provide key facts to individuals (and family) 
diagnosed with heart failure, to aide in their ability to stay active and well. Our education will focus on 
medication adherence, symptom recognition and management, communicating to your care team and 
lifestyle habits that can contribute to healthy living. 
1. Participants will be able to identify the most common symptoms related to heart failure and 
recognize the importance of sharing specific changes in these symptoms to their doctor or care 
team or nurse navigator; to help with management and optimization of their disease.  
2. Participants will become familiar with the names of their heart failure medications, maintain an 
accurate list of the medications and doses and co-create actions to ensure they take these 
medications daily.  
3. Participants will gain knowledge about safe, regular activity and food choices that can impact 
their weight and heart failure symptoms. 
Data Collection and Surveys 
See “Study Schematic” Section for a visual overview of the study. 
Patients will be surveyed for baseline demographics and study outcomes. Medical history, including labs, 
procedures, and diagnoses will be collected from the medical record and recorded in REDCap 
At consent, subjects will be surveyed for demographics that cannot be obtained from the medical record 
(See “Baseline Demographics” attachment). 
Quality of life will be collected through the patient-facing AMAZE app (See “KCCQ” attachment). 
Patient satisfaction will be collected through MAUQ (attached) administered through the app. The app 
will also track patient medication adherence, and facilitate symptom, blood pressure, weight, and activity 
tracking. 
At roughly 30 days from enrollment and again at 60 days from enrollment, a research coordinator will call 
the patient to collect 1) current cardiac medications and any changes to medication regimen and 2) 
hospitalizations, ED presentations, urgent care visits, primary care or cardiology visits, and cardiac rehab 
enrollment at institutions outside MGB. Research coordinators will review subject medical records to 
determine these events at MGB.  
EHR data for the control populations (MGH and BWH) will be obtained from RPDR. We may also 
review medical records for these patients to collect/confirm EHR data.  
Optional interviews 
Two rounds of interviews regarding the user experience of the AMAZE app may be conducted over the 
course of the study. The interview questions ask about usability and helpfulness of the app, along with the 
option to give feedback about technical issues and features that could use improvement. These interviews 

are optional and do not affect the participants’ overall participation in the study. This is reflected in the 
consent form, with a section allocated to participants’ choice of whether they would like to be contacted 
for these interviews or not.  
Participants who consent to being contacted for the interviews will be selected based on engagement with 
the app. We will measure engagement by percentage of daily log compliance over the past seven days. 
Participants who fill out the daily log more than half the days in a week will be classified as “engaged 
with the app” and those who fill out the daily log less than half the days in a week will be categorized as 
“disengaged with the app.”   
Research coordinators will conduct the two rounds of interviews at the 30- and 60-day follow-up calls 
respectively and record responses in REDCap. We will select four participants who are engaged with the 
app and one who is not to interview at their 30-day follow-up call. These same five participants will be 
interviewed at their 60-day follow-up call. A separate group of five participants, four who are engaged 
with the app and one who is not, will be interviewed only at their 60-day follow-up call.   
Study Closeout and Post Study Follow-up 
Ongoing participation is voluntary; patients can stop using the app at any time and withdraw from the 
study with no associated risk. Study staff will not withdraw participants from the study based on a lack of 
engagement with the app. When participants withdraw or complete the study, the nurse will send patients 
an off-boarding summary with the most current clinical recommendations from their care team, symptom 
reporting tips and most current prescribed medications. We will send the off-boarding summary to 
patients via Patient Gateway or email.  
 
A separate message will be sent to the cardiology care team to notify them of the participant’s status 
change in the study. Subjects will be reminded during the 60-day phone call that they should delete the 
AMAZE app. For participants who do not delete the application, the ability to use the app will end once it 
is deactivated via BrightInsight, Inc. due to withdrawal or completion of the pilot study. 
 
 
Clinician Surveying 
At the close of the study (60 days) a brief survey will be sent to all MGH cardiology physicians and nurse 
practitioners related to knowledge of and/or use of the AZ-DMP provider platform. The survey will be 
sent via email with a link to complete the questions in REDCap.  Since the online clinician surveying 
presents no more than minimal risk of harm to subjects and involves no procedures for which written 
consent is normally required outside of the research context, the consent procedure will include providing 
subjects (clinicians) with a written statement about the research followed by an option to click a button 
that states “I agree to participate in this research” or “I do not agree.” This written statement will appear at 
the beginning of the REDCap survey (see "MAUQClinicianSurvey_RedCap” attachment). If the clinician 
chooses “I do not agree,” the survey will end. If the clinician chooses “I agree to participate in this 
research,” the survey will advance to the branching logic displayed below: 

 
RISKS TO SUBJECTS 
This study involves participant-completed measures for information purposes only; the study does not 
involve the use of an investigational drug or device. There are no known risks or benefits to participants.  
Patients may become more aware of how they feel about their condition—and how their condition may 
affect certain aspects of their life. Patients will be encouraged to talk with their heart failure provider 
about their questions or concerns. The elements of federal regulations pertaining to consent procedures, 
disclosure of potential risks and benefits, and patient confidentiality will be strictly observed. 
 
Since the study involves adding a mobile health component to a treatment plan, risks posed to subjects are 
similar to those involved with following a HF discharge care plan. Subjects will be encouraged to contact 
the nurse navigator, their care team (physician or NP) with medical questions. 
 
There is a small risk of unauthorized access of subject data in this study, which will be minimized by 
keeping patient health information in a secure database. Only study personnel who have undergone the 
proper human research training will have access to this data. 
 
A Vendor Information Security Plan (VISP) (see “VISP_BrightInsight_Modular Final” attachment) was 
completed to evaluate the capacity of BrightInsight, Inc. to protect personally identifiable research data 
and other confidential information. In summary, BrightInsight is committed to the security and privacy of 
the platform and the digital solutions being built on top of the platform, whereby minimizing the risk for 
Astra Zeneca and Partners Health Care. To meet that end, BrightInsight has the following security and 
privacy certifications: 
• 
HIPAA Compliant 
• 
HITRUST CSF v9.1 
• 
HITRUST Certification of the NIST Cybersecurity Framework 
• 
ISO / IEC 27001: 2013 
• 
EU-Swiss Privacy Shield  
• 
Swiss-EU Privacy Shield 
• 
GDPR Compliant 
• 
French HDS Certification (waiting for certificate) 
For medical appropriateness, a message does appear within the app consistent with other messaging tools 
instructing patients not to use the messaging system for medical emergencies. See language used below. 
 

DISCLAIMER: Messages are not for medical emergencies. For medical emergencies call 911 
immediately.  
 
 
 
IV. 
PRIVACY AND CONFIDENTIALITY 
 
Study Data 
 
MGH 
Screening and enrollment logs will be kept in the study e-regulatory binder in MGB Dropbox for 
Business. Study subject data will be kept in a password protected database (REDCap); subject records 
will be linked to unique subject IDs. Only study personnel who have undergone the proper human 
research training will have access to these data. Computers that will be used to access and analyze the 
data the data include MGB build computers, MGB Purchased Laptops, or study staff Personal Laptops 
encrypted to MGB standards.  
 
Data for BWH controls will be obtained through RPDR/chart review, and stored in the study e-regulatory 
binder in Partners Enterprise Dropbox. 
 
Data collected through the patient facing app that is sent to the sponsor (described below) will also be sent 
to MGH by BrightInsight to research staff via MGB secure file transfer 
https://rc.partners.org/kb/article/2729). 
 
Sponsor 
Summary metrics from recruitment data will be shared with the sponsor, including the percentage who 
joined the study out of those eligible, reasons patients did not join the study, and the demographics of 
eligible patients. Summary metrics and study results will be shared with the sponsor, but the individual 
level subject data collected in REDCap will not. Additionally, aggregated summary information about the 
controls used in the study will be shared with the sponsor, but individual-level control data will not be 
shared. 
 
Data collected by the AMAZE™ app from the patient’s medical record: their demographics including zip 
code, appointment information including dates and locations of appointments, PCP information, 
conditions and the dates associated with them, and their medications will be sent to the sponsor by 
BrightInsight. Additionally, information collected by the app directly from the app: user metrics, message 
information (not the content of the message), survey responses (KCCQ and MAUQ), and other tracked 
information: medication adherence, and facilitate symptom, blood pressure, weight, and activity tracking, 
will all be sent to the sponsor by BrightInsight. This information is included in the document 
“BrightInsight Data” attached. 
 
V. 
EXPECTED BENEFITS 
We hope that this study will help us better understand and improve heart failure management remotely via 
enhanced access to care and communication between the patient and the care team, using the patient App 
and provider dashboard.  During the time between hospital discharge and a heart failure follow-up 
appointment, it is critical for patients to comply with the diet and exercise advice given to them and take 
their medications as prescribed. This study will help us better understand patient compliance with these 
activities when they leave the hospital, and guide future studies on patient mobile health application 
usage. We hope this study will also lead to development of better strategies to coordinate care between 
the time of discharge, the next follow up appointment and beyond. Potential benefits to subjects from this 

study might include increased medication adherence and better adherence to health behaviors associated 
with decreased heart failure disease risk.  
 
 
 
VI. 
 POWER ANALYSIS  
Our primary outcome will focus on changes in the patient’s quality of life over the study period. This will 
be quantified by patients’ Kansas City Cardiomyopathy Questionnaire scores. Using the pwr package in 
R, we have calculated greater than 80 percent power to detect at least a 0.40 SD change in KCCQ scores 
from the beginning to the end of the 60-day study period. 
 
VII. 
REFERENCES 
  
American Heart Association. (n.d.). Heart Failure. Retrieved October 20, 2020, from 
https://www.heart.org/en/health-topics/heart-failure 
 
Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and 
stroke statistics—2019 update: a report from the American Heart Association. Circulation. 
2019;139(10):e56–528. 
Board of Regents Univeristy of Wisconsin System. (2019). Learning Objectives. Retrieved December 4, 
2020, from http://ce.uwex.edu/wp-content/uploads/2015/02/LearningObjectives.pdf 
 
Centers for Disease Control and Prevention, National Center for Health Statistics. Underlying Cause of 
Death, 1999–2017. Accessed January 7, 2019. 
Chow CK, Redfern J, Hillis GS, Thakkar J, Santo K, Hackett ML, Jan S, Graves N, de Keizer L, Barry T, 
Bompoint S, Stepien S, Whittaker R, Rodgers A and Thiagalingam A. Effect of Lifestyle-Focused Text 
Messaging on Risk Factor Modification in Patients With Coronary Heart Disease: A Randomized Clinical 
Trial. JAMA : the journal of the American Medical Association. 2015;314:1255-63. 
Davis, Fred D. “User Acceptance of Information Technology: System Characteristics, User Perceptions 
and Behavioral Impacts.” International Journal of Man-Machine Studies, vol. 38, no. 3, 1993, pp. 475–87. 
Crossref, doi:10.1006/imms.1993.1022. 
Guo Y, Wang H, Zhang H, Liu T, Liang Z, Xia Y, Yan L, Xing Y, Shi H, Li S, Liu Y, Liu F, Feng M, 
Chen Y, Lip GYH and Investigators MI. Mobile Photoplethysmographic Technology to Detect Atrial 
Fibrillation. Journal of the American College of Cardiology. 2019;74:2365-2375. 
Hamilton SJ, Mills B, Birch EM and Thompson SC. Smartphones in the secondary prevention of 
cardiovascular disease: a systematic review. BMC Cardiovasc Disord. 2018;18:25. 
Home | CardioSmart – American College of Cardiology. (n.d.). Retrieved October 20, 2020, 
from https://www.cardiosmart.org/ 
Home | HFSA. (Unknown). Retrieved October 20, 2020, from https://hfsa.org 

Huang, W., Teng, T. ‐. H. K., Tay, W. T., Richards, A. M., Kadam, U., Lawson, C. A., Lam, C. S. P. 
(2020). Patient‐reported outcomes in heart failure with preserved vs. reduced ejection fraction: focus on 
physical independence. ESC Heart Failure, 7(5), 2051–2062. https://doi.org/10.1002/ehf2.12950 
Martin SS, Feldman DI, Blumenthal RS, Jones SR, Post WS, McKibben RA, Michos ED, Ndumele CE, 
Ratchford EV, Coresh J and Blaha MJ. mActive: A Randomized Clinical Trial of an Automated mHealth 
Intervention for Physical Activity Promotion. J Am Heart Assoc. 2015;4. 
McConnell MV, Shcherbina A, Pavlovic A, Homburger JR, Goldfeder RL, Waggot D, Cho MK, 
Rosenberger ME, Haskell WL, Myers J, Champagne MA, Mignot E, Landray M, Tarassenko L, 
Harrington RA, Yeung AC and Ashley EA. Feasibility of Obtaining Measures of Lifestyle From a 
Smartphone App: The MyHeart Counts Cardiovascular Health Study. JAMA Cardiol. 2017;2:67-76. 
Morrow, David A., et al. “Clinical Outcomes in Patients With Acute Decompensated Heart Failure 
Randomly Assigned to Sacubitril/Valsartan or Enalapril in the PIONEER-HF Trial.” Circulation, vol. 
139, no. 19, 2019, pp. 2285–88. Crossref, doi:10.1161/circulationaha.118.039331. 
Neubeck L, Lowres N, Benjamin EJ, Freedman SB, Coorey G and Redfern J. The mobile revolution--
using smartphone apps to prevent cardiovascular disease. Nat Rev Cardiol. 2015;12:350-60. 
Perez MV, Mahaffey KW, Hedlin H, Rumsfeld JS, Garcia A, Ferris T, Balasubramanian V, Russo AM, 
Rajmane A, Cheung L, Hung G, Lee J, Kowey P, Talati N, Nag D, Gummidipundi SE, Beatty A, Hills 
MT, Desai S, Granger CB, Desai M, Turakhia MP and Apple Heart Study I. Large-Scale Assessment of a 
Smartwatch to Identify Atrial Fibrillation. The New England journal of medicine. 2019;381:1909-1917. 
Verma, S. (2013, September 25). E learning,How to develop eLearning from start to end. Retrieved 
December 4, 2020, from  
https://www.slideshare.net/satishverma66/e-learninghow-to-develop-elearning-from-start-to-end 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

VIII. STUDY SCHEMATIC 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion criteria:
•
HF patients (> 21 years) admitted to 
MGH cardiology services (Ellison 
10 and 11)
•
Must own smartphone
•
Follow-up with MGH cardiologist
•
Discharged to home care
Exclusion criteria:
•
Cognitive impairment
•
Non-English speaking
•
Palliative management
•
Incarcerated
Screening
•
Consent
•
Download AMAZE app
•
Set up AMAZE account
Enrollment (n=50)
Patient discharged home
APP
RESEARCH
30-day 
KCCQ 
entered into
app
Baseline 
KCCQ 
entered into
app
•
Demographics
•
Vital signs
•
Medical history and co-
morbidities
•
Laboratory data
•
Prescribed medications
Baseline
30-day follow up call
•
Hospital, ED, urgent care, 
physician visits
•
Enrollment in cardiac rehab 
program
•
Adherence to prescribed 
medications
60-day follow up call
•
Hospital, ED, urgent care, 
physician visits
•
Enrollment in cardiac rehab 
program
•
Adherence to prescribed 
medications
•
Deletion of app
•
Initiate health coaching
•
Patient engages with DMP
•
Providers monitor patient-
derived data
Within first week
•
Patient enters information into 
daily tracking log, keeps track 
of appointments and 
medications
•
Weekly communication 
between patient and Nurse 
Navigator
•
Providers message patients, 
coordinate care, and adjust 
medications if needed
Duration of study
60-day KCCQ 
and MAUQ 
entered into app
Study completion
MAUQ sent to providers 
via REDCap
Outcomes assessed
•
Primary outcome: change in quality of life
•
Exploratory outcomes: 
Improvements in quality of care delivered
Patient and provider satisfaction
Change in 30- and 60-day hospital readmissions
Use of healthcare resources
Optional interviews about 
user experience – conducted 
by CRCs, incorporated into 
follow-up calls. 
5 participants interviewed 
after about 30 days of 
using the app 
Original 5 participants 
interviewed after about 
60 days of using the app.
5 new participants 
interviewed after about 
60 days of using the app
CLINICAL