Home Telemonitoring In Patients After Myocardial Infarction, HELP ME Trial
Phase: NA
Conditions: Myocardial Infarction, Heart Attack
Sponsor: Mayo Clinic

 
 
Home Telemonitoring In Patients after 
Myocardial Infarction Experience, HELP ME trial 
 
NCT04664881 
 
27December2024 

PROTOCOL 20-001646 
Full Title: Home Telemonitoring In Patients after Myocardial Infarction Experience, HELP ME trial.   
 
Principal Investigators: 
Joerg Herrmann, MD 
 
Co-Principal Investigators: 
Meir Tabi, MD 
 
Study Intervention Provided by: SHL Telemedicine Ltd, Israel.  
 
Version 9 (Please change version number with each amendment) 
December 27, 2024 
1. 
Study summary................................................................................................................... 1 
2. 
Study TEAM ROASTER .................................................................................................... 1 
3. 
Study objectives ................................................................................................................. 2 
3.1 
Primary Objective ................................................................................................................................. 2 
3.2 
Secondary Objectives .......................................................................................................................... 2 
4. 
BACKGROUND AND RATIONALE ................................................................................. 2 
4.1 
Background ........................................................................................................................................... 2 
4.2 
Study Rationale .................................................................................................................................... 3 
5. 
STUDY DESIGN................................................................................................................... 3 
6. 
SELECTION AND ENROLLMENT OF PARTICIPANTS .............................................. 5 
6.1 
Inclusion Criteria ................................................................................................................................... 5 
6.2 
Study Enrollment Procedures ............................................................................................................ 5 
7. 
STUDY INTERVENTIONS ................................................................................................. 5 
Interventions, Administration, and Duration ................................................................................................. 5 
8. 
STUDY PROCEDURES ...................................................................................................... 6 
8.1.1 Screening Evaluation ......................................................................................................................... 6 
8.1.2 Enrollment, Baseline, and/or Randomization ................................................................................ 6 
8.1 
Schedule of Evaluations ...................................................................................................................... 7 
9. 
STATISTICAL CONSIDERATIONS ................................................................................. 8 
9.1. 
General Design Issues ........................................................................................................................ 8 
9.2. 
Sample Size and Randomization ...................................................................................................... 8 
9.4. 
Interim Analyses and Stopping Rules ............................................................................................... 8 

Page ii of 23 
 
9.5. 
Outcome measures .............................................................................................................................. 9 
9.5.1. 
Primary trial objective .................................................................................................................. 9 
9.5.2. 
Secondary trial objective ............................................................................................................. 9 
9.6. 
Data Analyses ....................................................................................................................................... 9 
10. DATA COLLECTION AND QUALITY ASSURANCE ................................................... 9 
10.1. 
Data Collection Forms ..................................................................................................................... 9 
10.2. 
Data Management .......................................................................................................................... 10 
10.3. 
Quality Assurance .......................................................................................................................... 10 
10.3.1 
Training ........................................................................................................................................ 10 
10.3.2  Quality Control Committee ........................................................................................................ 10 
10.3.3  Metrics .......................................................................................................................................... 10 
10.3.4  Protocol Deviations .................................................................................................................... 11 
10.3.5 
Monitoring .................................................................................................................................... 11 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY..................................................... 11 
11.1. 
Institutional Review Board (IRB) Review .................................................................................... 11 
11.2. 
Informed Consent Forms .............................................................................................................. 11 
11.3. 
Participant Confidentiality ............................................................................................................. 12 
11.4. 
Study Discontinuation .................................................................................................................... 12 
12. ETHICAL CONSIDERATIONS ........................................................................................ 12 
13. COMMITTEES .................................................................................................................... 12 
14. PUBLICATION OF RESEARCH FINDINGS ................................................................. 12 
15. REFERENCES ................................................................................................................... 13 
SUPPLEMENTS/APPENDICES ............................................................................................. 15 
Appendix A ................................................................................................................................ 15 
Data and Safety Monitoring Plan ......................................................................................... 15 
Appendix B ................................................................................................................................ 17 
DSMP Sample Study Report Outline................................................................................... 17 
 
 

LIST OF ABBREVIATIONS 
ACC 
American College of Cardiology 
AHA 
American Heart Association 
AMI 
CICU 
CRF 
Acute Myocardial Infarction 
Cardiac Intensive Care Unit 
Case Report Form 
DSMB 
Data and Safety Monitoring Board 
ECG 
ED 
FDA 
Electrocardiogram 
Emergency Department 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ITT 
Intent to Treat 
IRB 
Institutional Review Board 
LVD 
Left Ventricular Dysfunction 
LVEF 
Left Ventricular Ejection Fraction 
MACE 
Major Adverse Cardiovascular Events 
MI 
NP 
PA  
Myocardial Infarction 
Nurse Practitioner 
Physician Assistant  
PHI 
Protected Health Information 
PI 
Principal Investigator 
US 
United States  
USA 
United States of America  

Page 1 of 23 
 
1. STUDY SUMMARY 
Title 
Home Telemonitoring In Patients after Myocardial Infarction 
Experience, HELP ME trial. 
Methodology 
Randomized, parallel-group clinical trial in acute coronary syndrome 
patients which have undergone coronary angiography with two study 
groups:  
Group 1: Discharged home with standard medical treatment. 
Group 2: Discharged home with standard medical treatment and 12 
lead ECG telemonitoring device for 90 days. 
 
Overall Study 
Duration 
2 years  
Subject Participation 
Duration 
90 days  
Single or Multi-Site  
Single Site Mayo Clinic Rochester, MN  
Objectives 
Several retrospective studies indicate that patients with ACS post PCI 
have less readmissions and better survival with 12 lead ECG 
telemonitoring at home. So far, no prospective study was done to show 
this benefit. 
The objective of the current study is to evaluate the incidence of ED 
visits, re-hospitalizations and major adverse cardiovascular events 
(MACE including cardiovascular death and hospitalization for 
myocardial infarction, unstable angina, repeat revascularization, heart 
failure, stroke, arrhythmias, and cardiac arrest), and cost-effectiveness 
over  a period of 90 (+/- 7) days after an index hospitalization for  an 
acute myocardial infarction (MI).  
Our central hypothesis is that 12 lead ECG home telemonitoring 
decreases general and cardiac ED presentation and hospital 
readmission rates without an increase in MACE and at a lower health 
care utilization cost compared to patients with standard therapy alone.   
Three specific aims will be pursued: 
 
Aim 1: To compare the rates of ED visits and re-hospitalization rates as 
well as related downstream cardiovascular testing (echocardiogram, 
stress test or coronary CT, or invasive coronary angiogram)  from 
discharge after index hospitalization for MI to 90 days follow-up 
between patients undergoing standard care alone or standard care plus 
the home 12 lead ECG telemonitoring device   
 
Aim 2: To compare the rates of MACE from discharge after index 
hospitalization for MI to 90 days follow-up between patients undergoing 
standard care alone or standard care plus the home 12 lead ECG 
telemonitoring device  
 
Aim 3: To compare health care cost utilization from discharge after 
index hospitalization for MI to 90 (+/-7) days follow-up between patients 
undergoing standard care alone or standard care plus the home 12 
lead ECG telemonitoring device  
Number of Subjects 
240 patients in total, enrolled over one-two years  

Page 2 of 23 
 
Inclusion and 
Exclusion Criteria 
Inclusion criteria:  
• 
≥18 years of age,  
• 
Acute myocardial infarction, both STEMI and non-STEMI  
• 
Able to use the home ECG telemonitoring 
• 
Must have smartphone device with home wi-fi/mobile internet 
which allows 24/7 ability to transmit ECG 
• 
Caring family member who will be able to help/perform the ECG 
in case the patient himself won’t be able to do it  
• 
Planned to be discharged home by the treating team 
 
Exclusion criteria: 
• 
No ability to use the device at home   
• 
No smartphone device or home wi-fi/mobile internet which 
prevent 24/7 ability to transmit ECG 
• 
Cannot download the smartheart app  
• 
No support in home environment  
• 
Out of hospital cardiac arrest: secondary to a non-shockable 
rhythm, unrelated to an acute coronary syndrome, or with any 
level of neurologic damage.  
• 
Resident of nursing home or acute care facility 
• 
Uninterpretable ECG at discharge – left bundle branch block 
(LBBB), pacemaker or implantable cardioverter defibrillator 
(ICD) with pacing dependence.  
• 
Patients who are planned for staged PCI after the index 
hospitalization   
Study Product, 
Dose, Route, 
Regimen 
Prior to discharge patients will be 1:1 randomized to standard medical 
therapy or standard medical therapy + 12 lead ECG Smartheart 
telemonitoring device.  
Duration of 
Administration 
Patients will receive the device for the period of 90 (+/-7) days .  
Reference therapy 
Group 1 will serve as the reference group 
Statistical 
Methodology 
Inter-group differences in the rates of the primary combined endpoint 
will be analyzed by the Chi square test.  

Page 2 of 23 
 
3. STUDY OBJECTIVES 
3.1 Primary Objective 
The primary objective of this trial is to compare the rates of ED visits and re-hospitalization rates as well as 
related downstream cardiovascular testing (echocardiogram, stress test or coronary CT, or invasive coronary 
angiogram) from discharge after index hospitalization for MI to 90 (+/-7) days follow-up between patients 
undergoing standard care alone or standard care plus the 12 lead ECG Smartheart home telemonitoring 
device. 
3.2 Secondary Objectives 
The secondary objectives of this study are: 
a) To compare the rates of cardiovascular and non-cardiovascular ED visits and re-hospitalizations rates, 
from discharge after index hospitalization for MI to 90 (+/-7)days follow-up between patients undergoing 
standard care alone or standard care plus the 12 lead ECG Smartheart home telemonitoring device. 
 
b) To compare the rates of downstream cardiovascular testing (echocardiogram, stress test or coronary 
CT, or invasive coronary angiogram) from discharge after index hospitalization for MI to 90 (+/-7) days 
follow-up between patients undergoing standard care alone or standard care plus the 12 lead ECG 
Smartheart home telemonitoring device. 
 
c) To compare the rates of MACE from discharge after index hospitalization for MI 90 (+/-7) days follow-
up between patients undergoing standard care alone or standard care plus the 12 lead ECG 
Smartheart home telemonitoring device. 
  
d) To compare health care cost utilization (including all cardiovascular inpatient and outpatient office visits 
and tests) from discharge after index hospitalization for MI to 90 (+/-7)days follow-up between patients 
undergoing standard care alone or standard care plus the 12 lead ECG telemonitoring device. 
e) To compare quality of life (MacNew Heart Disease Questionnaire) from discharge after index 
hospitalization for MI to 90 (+/-7) days follow-up between patients undergoing standard care alone or 
standard care plus the 12 lead ECG telemonitoring device. 
 
4. 
BACKGROUND AND RATIONALE  
4.1 Background  
Survivors of a first acute myocardial infarction (AMI) face a substantial risk of further major adverse 
cardiovascular events (MACE), including death, recurrent MI, heart failure, arrhythmias, angina, and stroke. 
The rate of rehospitalization within 30 days after acute MI is reported to range between 17 and 25 percent 
[1,2]. In a single-community study, Olmsted County, Minnesota, United States, of 3010 patients who were 
hospitalized for a first-ever MI (STEMI – 31%) rehospitalization within 30 days occurred in about 19 percent [3]. 
Across the broad spectrum of patients with acute myocardial infarction (MI), short-term (in-hospital or 30-day) 
mortality has been decreasing over the past 30 years, concomitantly with the increasing use of reperfusion 
strategies and proven preventative therapies such as beta blockers, aspirin, and statins [4-12]. The 30-day 
mortality after all acute coronary syndromes (ST-elevation myocardial infarction [STEMI], non-ST elevation 
myocardial infarction [NSTEMI], and unstable angina) is less than 5 percent [13]. The incidence of SCD after 
acute MI is the same with STEMI and NSTEMI [4,14]. Among patients who have had an MI and are followed 
for about four years, approximately one-half of sudden deaths occur in the first year and one-quarter in the first 
three months [15,16]. The risk is markedly increased in patients with a left ventricular ejection fraction ≤35 
percent. Additional important aspect following acute MI [AMI] is financial, although mortality attributable to AMI 
has declined, 30-day post-AMI readmission rates remain high (median 19.9%) and carry a heavy economic 
burden, accounting for 21,000 admissions at a cost of 136 million dollars in the United States [17]. 
 
‘‘SHL’’-Telemedicine is a call center that was established in 1987 in Israel. It operates 24 hours/day, 365 days 
a year, and is managed by a medical staff. Each subscriber’s medical file (which also includes a full 12-lead 

Page 3 of 23 
 
electrocardiogram [ECG]) is electronically stored and continuously updated. The subscribers carry a 
SmartHeart 12 lead ECG device by which they can transmit a full 12-lead ECG via internet by a designated 
smart application and call the SHL center, the archived information is uploaded within seconds on a monitor 
together with the real-time transmitted information, and the staff evaluates the caller’s medical status according 
to the transtelephonic anamnesis, newly transmitted ECG data, and pertinent facts from the electronic file. By 
integrating computerized algorithms and clinical judgment, the staff advises the subscriber which steps to take 
and which action the staff will take according to predefined standing orders and protocol [18]. Several 
retrospective studies showed favorable clinical outcomes of patients using ‘‘SHL’’-Telemedicine and 
Smartheart device, including reduction in a 30-day readmission rate, shorter time lag between the onset of 
symptoms and contacting medical assistance and lower mortality rates[18-20].  
 
 
4.2 Study Rationale 
This study will be pursued as a prospective clinical trial building upon and extending the available evidence of 
the use of outpatient ECG monitoring after MI outlined above. We will test the clinical and economic impact of 
the SHL-telemonitoring cardiac device during the first 90 days after MI in a defined health care environment. 
The current standard of care is antiplatelet agents, beta blockers and statins alone, with a reported re-
hospitalization rate of 17-25%. In addition to the standard care, patients in the intervention arm will be 
instructed on how to use the device and send ECG to a Mayo Clinic CICU designated study NP/PA, which will 
be in communication with the participant to respond to recordings taken for symptom review. Patients with a 
true acute cardiac event will be advised to seek medical assistance immediately, in case of STEMI, VT/VF or 
CAVB the EMS will be sent to the participant. Patients with reassuring ECG and low suspicion of acute cardiac 
event will be advised to postpone medical assistance and to avoid unnecessary emergency department [ED] 
visits. Such an approach may improve patient outcomes and reduce costs at the same time.  
Additionally, the COVID-19 pandemic brought its challenges to the health systems worldwide, those are 
uncertain times and prevention of unnecessary ED visits and readmissions after discharge would be beneficial, 
in particularly for patients post AMI having comorbidities.  
 
It is important to emphasize that the device is safe to use and this is a very low risk study with a large potential 
benefit of decrease in unnecessary readmission rates, subsequent costs and early detection of real cardiac 
abnormalities with prompt medical assistance could improve outcomes. This study is planned to address the 
importance of home telemonitoring in cardiac patients and could have future implications on the current 
guidelines and standard care.  
 
5. 
STUDY DESIGN 
This study will be conducted as a prospective, randomized pilot study in patients with acute myocardial 
infarction which have undergone coronary angiography with two study groups (Figure 1):  
- 
Group 1 (control group): standard clinical practice medical therapy at discharge, including double 
antiplatelet therapy (DAPT), high potency statins and if indicated, beta blockers.   
- 
Group 2 (intervention group): standard clinical practice medical therapy as above plus the 
Smartheart home-telemonitoring 12 lead ECG device.  
 
Figure 1: Trial outline 
 
 
 
 
 
 
 
 
 
 
 
 

Page 4 of 23 
 
 
Patients will be randomized at discharge to standard medical therapy (DAPT, high potency statins and beta 
blockers) or the standard medical therapy plus the Smartheart home-telemonitoring 12 lead ECG device. The 
intervention group will have instructions and explanation, prior discharge, how to use the device and will be 
guided to have two device testing’s at home during the first two weeks after discharge. In case of any 
symptoms, including but not limited to chest pain, shortness of breath, sensation of irregular heart beats and 
near fainting during the 90 days post discharge the patient will record a 12 lead ECG at home and transmit it 
directly to Saint Mary’s Hospital CICU designated study NP/PA, which is available 24/7, the ECG will be read 
by the NP/PA (with the support of the CICU consultant). Communication with the patient will be through the 
study designated CICU NP/PA, which will call the participant, record short history of the medical emergency 
and provide the patient with appropriate directions according to the ECG finding, medical urgency and study 
protocol. The CICU NP/PA will call the patient as soon as possible after receiving the ECG to the study email 
inbox.  
 
In case of delay with conducting the phone call to the participant, >15 minutes from sending the ECG, or 
having any technical issues with recording the ECG, the participant will call to a study phone (number provided 
to the participant) carried by CICU NP/PA which is available 24/7.  An alternative phone number will also be 
provided that will get the patient in touch with the Mayo Clinic operator who can then direct the patient to the 
Cardiac Intensive Care Unit (CICU) NP/PA staff.  Patients will be instructed to use this if they are unable to 
reach the NP/PA staff directly with the previously provided phone number.  In case the technical issue was not 
solved by the NP/PA, the recommendation for the patient will be based on the symptoms characteristics (as 
described in the NP/PA decision making tool).  In case the participant cannot be reached by the primary phone 
number provided, NP/PA will call second provided phone number (of patients’ related individual/significant 
other), in case there is no response to both phone numbers, and the participant did not call our NP/PA 
designated phone, further decisions will be based on the ECG tracing. If alarming findings are present, which 
may explain a loss of consciousness, EMS will be activated to the home address of the patient, assuming that 
patients will use the ECG device at home. If no alarming finding is present the patient will be reassured with a 
phone follow-up the next day. 
 
Adverse Event Reporting 
We will only be collecting adverse events that result in Cardiovascular Events, Emergency Department visits, 
and Hospitalizations, which will be looking at the outcomes, as this is a monitoring study, with no adverse 
events expected from the device (SmartHeart, which is FDA approved), as all other events are not relevant to 
the research study. To make sure assessments are consistent throughout the study, this will also be followed 
retrospectively. 
 
 
 
 

Page 5 of 23 
 
6. 
SELECTION AND ENROLLMENT OF PARTICIPANTS  
6.1 Inclusion Criteria  
• 
≥18 years of age,  
• 
Acute myocardial infarction, STEMI and 
NSTEMI  
• 
Ability to use the device at home  
• 
Must have smartphone device with 
home wi-fi/mobile internet which allow 
24/7 ability to transmit ECG 
• 
Caring family member who will be able 
to perform the ECG in case the patient 
himself won’t be able to do it 
 
6.2 Exclusion criteria 
• 
<18 years of age 
• 
No ability to use the device at home / 
Unable to comply with the device 
instructions 
• 
No smartphone device or home wi-
fi/mobile internet which prevent 24/7 
ability to transmit ECG 
• 
Unable to download the smartheart 
application  
• 
No support in home environment  
• 
Out of hospital cardiac arrest 
• 
Resident of nursing home or acute care 
facility 
• 
Uninterpretable ECG at discharge – left 
bundle branch block, pacemaker dependence, implantable cardioverter defibrillator. 
• 
Out of hospital cardiac arrest: secondary to a non-shockable rhythm, unrelated to an acute coronary 
syndrome, or with any level of neurologic damage.  
• 
Patients who are planned for staged PCI after the index hospitalization 
 
6.2 Study Enrollment Procedures  
This study will be conducted on a study platform that is already in place at the Mayo Clinic Rochester, Patients 
identified with a diagnosis of acute myocardial infarction and subsequent coronary angiography with will be 
enrolled. Any potential study candidates will be identified based on the eligibility criteria listed above. A 
screening log will be kept and secured electronically. Those potentially eligible will be recorded by clinic 
number and exclusion criteria will be checked. If any are met, the specific reason will be marked, otherwise a 
commentary will be entered for those who are eligible but do not wish to participate. Those patients who agree 
to participate will be asked to provide written consent. The study details will be outlined. It will be made clear 
that at this point there are no data whether the intervention approach leads to superior clinical outcomes and 
this very fact provides the rationale for this trial.  
 
7. 
STUDY INTERVENTIONS  
Interventions, Administration, and Duration  
Patients will be randomized to either standard medical therapy or standard medical therapy + Smartheart 
home telemonitoring device. The device will be supplied be the “SHL” telemedicine for each patient in the 
intervention group for the period of 90 (+/-7) days from the randomization. Patients will be followed for 90 (+/-7) 
days. At randomization and at the end of the study period the patients will be asked to fill out quality of life 
questionnaire and return back the Smartheart device by mailing back the device in the padded box covered by 
 
Figure 2. Call work-flow 
 

Page 6 of 23 
 
insurance in case it is damaged upon receipt to Mayo Clinic. Medications during the study period will be 
prescribed by the treating physician, no change of medications will be performed by the study team.  
The SmartHeart, developed by SHL Telemedicine Ltd., was approved by the FDA on 2012 (K113514). It is a 
personal, hand-held device, enabling an individual to immediately transmit a 12-lead ECG from anywhere and 
anytime, using a smart phone application, to a physician's office, hospital or monitoring center. The ECG 
output from Smartheart device was compared to standard 12 lead ECG recordings and was found to be 
reliable. Data will be labeled with a subject’s medical record number and by date of transmission. The data will 
be uploaded from Smartheart device to the US cloud (located in USA), and sent by email directly to designated 
Mayo Clinic CICU NP/PA smartphone devices email address. The smartphone device will be carried by the 
NP/PA 24/7 and will give a loud alert for every incoming ECG. The ECG data will be uploaded and accessible 
in the patient’s EPIC EMR. 
 
The smart phone application will send push notifications to the patients to remind them to perform test 
ECG at Week 1, Week 2, and Week 4 (optional, if patient has not performed Week 2 ECG). Patients will 
also be notified every other day after Week 1, if not completed. 
 
8. 
STUDY PROCEDURES 
8.1.1 Screening Evaluation 
Acute myocardial infarctions patients identified on cardiology service will be evaluated for enrollment. These 
patients will be approached by a trained research member who will present the background, rationale, and 
details of the study. A single informed consent form will be used that describes both the screening and study 
procedures. Those who consent will be asked additional questions of their past medical history and their 
records will be reviewed to identify any exclusion criteria. If any are present, these will be charted in the 
screening log. For those who are eligible but refuse, a comment will be added to the screening log detailing the 
reason for non-participation.  
8.1.2 Enrollment, Baseline, and/or Randomization 
All patients who consent to the study are considered to be enrolled as of the date of the consent.  
Baseline Assessments- comprises a review for any cardiovascular diseases or risk factors, home medications. 
Additional data will be collected: type of AMI (location: anterior, inferior, posterior, lateral), troponin levels, 
baseline ECG, left ventricular function by echocardiography, Canadian Classification scale (CCS) of Angina( 
class I, II, III IV)  .  
Randomization- will be done once all inclusion and exclusion criteria are reviewed and the patient meets 
eligibility criteria. Patient and treating cardiologist will be informed which study group the patient was assigned. 
Patients assigned to group 1 will be discharged with standard medical therapy as indicated by AHA/ACC 
guidelines in post AMI patients treated with or without PCI. Patients in group 2 will be discharged with the 
standard medical treatment as indicated by AHA/ACC guidelines in post AMI patients treated with or without 
PCI plus they will receive the Smartheart 12 lead ECG home telemonitoring device for the period of 90 days 
(+/-7). Those patients will have short explanation on how the device works, how to adjust it on the chest and 
how to transmit the ECG.  
 
A post-study questionnaire will be administered to patients randomized to the device group to collect feedback 
on their experiences with the device. Participation is voluntary, and responses will be anonymized to ensure 
confidentiality. The inclusion of this questionnaire will not impact the primary study objectives or patient safety. 
 
 
 
 
 
 
 

Page 8 of 23 
 
9. 
STATISTICAL CONSIDERATIONS  
9.1. General Design Issues  
This study will be conducted as a parallel group randomized clinical trial. The main goal is to define if 
Smartheart 12 lead ECG home device will decrease the rates of ED visits and rehospitalization in patients after 
index hospitalization for acute MI.  
Our central primary hypothesis is that the Smartheart 12 lead ECG home device will decrease the ED visits 
and rehospitalization rates, leading to subsequent decrease in healthcare costs. Additional potential benefit is 
decrease in mortality by identifying any cardiac emergency at the early stage with appropriate urgent medical 
assistance. The quality of life of patients with the Smartheart device at home could be improved, knowing there 
is an easily available tool which can provide quick and reliable diagnosis. 
 
9.2. Sample Size and Randomization 
Patients will be randomized to either standard medical therapy or the medical therapy plus the Smartheart 12 
lead ECG home device.  
 
The primary combined endpoint parameter is the rate of ED visits/rehospitalizations as well as related 
downstream cardiovascular testing (echocardiogram, stress test or coronary CT, or invasive coronary 
angiogram) at 90 (+/-7) days after discharge and mortality rates during the 90 (+/-7) days of follow up. Based on 
the most recent in-house registry data, we have about 50 AMI patients undergoing PCI a month. Accordingly, 
we have at least 600 patients a year who are discharged with a diagnosis of AMI from Saint Mary’s Hospital.  
 
Our own registry data further indicate that 24% of revascularized AMI patients will present to the ED or will be 
readmitted within 90 days. This is in keeping with the published literature citing a rate of 20-30%. Half of these 
patients will present for cardiovascular complaints and may get further testing, including echocardiogram, stress 
test or coronary CT, or invasive coronary angiogram. Having a 12-lead ECG available and the phone triage 
available to direct care may impact not only emergency presentation but also downstream testing. This will be 
considered in this trial, and each of these will be considered as a component to the combined primary endpoint 
event. Assuming that patients presenting with cardiovascular concern may receive two of the outlined 
downstream test as they present to the ED and hospital, the estimated event rate will be 48%. With 120 patients 
in each arm the study we would be adequately powered (beta error <0.2) to show a statistically significant (at 
alpha error levels of <0.05) for a 37.5% event reduction. 
 
9.3. 
Treatment Assignment Procedures 
A computer-generated randomization scheme will be utilized assigning each consecutive patient enrolled to 
one of the two groups. The randomization scheme is 1:1. Patients and providers are to adhere to the protocol. 
 
9.4. Interim Analyses and Stopping Rules 
Due to the uncertainty in proposed rehospitalization rate of the treatment arm, a sample size reestimation 
(SSR) will be performed after 60 patients have finished the study in the treatment group. The rate will be 
estimated only for the treatment group, and the sample size will be recalculated using the new calculated rate. 
The results of this calculation will be the new larger sample size for the study. If the calculation proposes a 
sample size that is smaller, the original 120 patients per group will be used.  No stopping rules are 
implemented for this pilot study. 
 
As an example, there may be more rehospitalizations and ER visits than expected in the treatment group. If the 
rehospitalizations and ER visits were 17.5% at 90 days, this would result in the sample size being increased to 
181/group. Alternatively, if the rehospitalizations and ER visits in the treatment group were 10%, the sample 
size required would only be 62/group. If this were to happen, the sample size for the study would be 
maintained at 120 per group. 
 

Page 9 of 23 
 
9.5. Outcome measures  
9.5.1. Primary trial objective 
The primary aim of the trial is to compare the cardiac ED visits and hospital readmission rates as well as 
downstream testing at 90 (+/-7) days after hospitalization for MI between group 1 and group 2. 
9.5.1.1. 
Primary outcome measures  
The combined primary endpoint of the trial is the rate of ED visits, hospital readmission, and any of the 
downstream testing modalities (echocardiogram, stress test or coronary CT, or invasive coronary angiogram) 
from discharge after index hospitalization for MI to 90 days of follow-up between group 1 and group 2. 
9.5.2. Secondary trial objective 
The second aim of the trial is to compare the individual endpoints of the primary endpoint, MACE rates, heath 
care utilization costs and quality of life between group 1 and group 2.  
9.5.2.1. 
Outcome measures  
• 
Rate of ED visit and rehospitalization, overall and related to cardiovascular and non-cardiovascular causes 
• 
Rate of downstream testing modalities (echocardiogram, stress test or coronary CT, or invasive 
coronary angiogram) 
• 
Rate of MACE as defined above 
• 
Amount of money in US dollars that was spent for any medical service related to cardiovascular and non-
cardiovascular diseases in both study groups.  
• 
Quality of life questionnaire score in both study groups at the time of enrollment and at 90 days. 
 
9.6. Data Analyses 
The primary analysis for Aim 1 (lead aim of the study) will be a comparison of the rates of the primary 
combined endpoint between group 1 and 2 via Chi square test for categorical data of independent samples. 
The test will be used for any other categorical data. For continuous data, an independent groups t-test or 
Wilcoxon as appropriate after testing distributional assumptions.  
 
10. DATA COLLECTION AND QUALITY ASSURANCE 
10.1. Data Collection Forms 
The study case report form (CRF) is the primary data collection instrument for the study. All data requested on 
the CRF must be recorded. All missing data must be explained. If a space on the CRF is left blank because the 
procedure was not done or the question was not asked, write “N/D”. If the item is not applicable to the 
individual case, write “N/A”. All entries should be printed legibly in black ink. If any entry error has been made, 
to correct such an error, draw a single straight line through the incorrect entry and enter the correct data above 
it. All such changes must be initialed and dated. Do not erase or use “white-out” for errors. For clarification of 
illegible or uncertain entries, print the clarification above the item, then initial and date it. If the reason for the 
correction is not clear or needs additional explanation, neatly include the details to justify the correction. 
The data collection tool for this study will be investigator-designed case report forms. The investigator will 
maintain complete and accurate study documentation in a separate file. Study documentation may include 
medical records, records detailing the progress of the study for each subject, signed informed consent forms, 
drug disposition records, correspondence with the study coordinator study monitor/sponsor, screening and 
consent information, severe adverse event reports, laboratory reports, subject diaries, data clarifications 
requested by the sponsor, and any other documentation deemed relevant and pertinent to the study and the 
study subjects.  Subject data necessary for analysis and reporting will be entered into a validated database or 
data system in accordance. Clinical data management will be performed in accordance with applicable data 
management vendor standards and data cleaning procedures. The investigator is responsible for the 
procurement of data and for the quality of data recorded on the CRFs. The handling of data, including data 
quality assurance, will comply with regulatory guidelines (e.g., ICH GCP). 

Page 10 of 23 
 
Source data is 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 the 
clinical trial. 
The investigator will maintain records and essential documents related to the conduct of the study.  These will 
include subject case histories and regulatory documents. 
10.2. Data Management  
All study data will be collected at Mayo Clinic with the Department of Cardiovascular Diseases as the primary 
coordinating and data management center.  
RedCap will be used for clinical data management and randomization. These tools are institutionally supported 
and allow for rapid database development. The implementation of the software within a project includes 
training on the system’s use, robust error checking, security considerations, and full audit trail. Balance, which 
is integrated into RedCap, allows for a variety of randomization and minimization algorithms. 
Demographic and clinical data will be extracted from medical records including age and gender, vital signs, 
physical exam findings.  
Data on clinical outcome/event reporting will include cardiac dysfunction and/or heart failure as well as major 
adverse cardiovascular events (including myocardial infarction, heart failure, arrhythmia, transient ischemic 
attack, and stroke). 
The echocardiographic parameters that will be captured comprise systolic, diastolic LV and RV function 
including LVEF.  
The angiographic parameters collected will include name of the coronary artery, degree of stenosis and 
location, number of diseased vessels and number of stents, PCI success and complications.  
All individually identifiable patient records and data will be stored in a database under coded accession 
numbers. A password is required to gain access to this protected and privileged information. Only the 
approved and trained study staff will have access to the database. The sponsor will not have any access to the 
study data.  For individuals providing data, e.g. core laboratory personnel, access will be limited to entering 
data only. All data are monitored regularly for entry and access, and a formal policy regarding protection of 
personal privacy is in place throughout Mayo Foundation. The key to identification of subjects will be 
maintained in a secure office environment under the direction of the investigators. The institutional commitment 
at Mayo Clinic to protect patients’ (and study participants’) privacy is a high priority. 
10.3. Quality Assurance  
10.3.1 Training 
The study will be performed only by adequately trained personnel. This applies to the entire study team 
roaster. Only approved and trained study staff, experienced in trials such as these, will interact with the 
patients and manage the data forms and database. As part of the study data, the study team will collect data 
on ECG, echocardiography and other imaging tests which are ordered per routine care for the patients during 
their hospitalization. 
10.3.2  Quality Control Committee  
This study will not assemble a quality control committee. 
10.3.3  Metrics  
The same applies for all endpoint parameters. Computerized checks will be performed to ensure data integrity. 
These will be reviewed by a trained study staff for fidelity. Source document verification will be performed to 
ensure data fidelity as well. To ensure compliance with GCP and all applicable regulatory requirements, the 
sponsor or designee may conduct a quality assurance audit. Regulatory agencies may also conduct a 
regulatory inspection of this study. Such audits/inspections can occur at any time during or after completion of 

Page 11 of 23 
 
the study. If an audit or inspection occurs, the investigator and institution agree to allow the auditor/inspector 
direct access to all relevant documents and to allocate his/her time and the time of his/her staff to the 
auditor/inspector to discuss findings and any relevant issues. 
10.3.4  Protocol Deviations 
Patients will be contacted by phone for the device testing several times during the first month. The next contact 
will occur by phone call at the end of the study (90 +/-7 days after the randomization). If any deviation from the 
study protocol were noted, a record will be made on their study participation form and these patients will be 
flagged for review by the PI. The study team will then decide if a study deviation occurred that precludes 
continuation of study participation. If this were indeed the case, the patient will be notified. This individual will 
be removed from the study and will be replaced by another study participant.   
10.3.5 Monitoring 
 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, the sponsor, and 
government regulatory agencies, 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 (e.g. pharmacy, diagnostic laboratory, etc.). 
Participation as an investigator in this study implies acceptance of potential inspection by government 
regulatory authorities and applicable compliance offices. 
 
11. PARTICIPANT RIGHTS AND CONFIDENTIALITY  
The study will employ standard methods for protecting the confidentiality of research materials through the use 
of coded identification numbers that are specific to the study on all materials except those that are necessary 
for participant contact, follow-up, and ongoing linkage with data such as those from medical records, using 
password-protected computer data files and databases, and locked file cabinets for storing hard copies of any 
other study materials. Only study personnel who need to track participants for follow-up purposes have access 
to the identifying information for individual study participants. No personally-identifiable information (protected 
health information) except the minimum necessary for study purposes are shared with co-investigators, and 
any sharing of data is by encrypted, password-protected data files. In addition to the procedures outlined 
above, confidentiality and privacy are further enhanced as each institution maintains research databases 
behind institution-specific password-protected firewalls. 
ECG recordings will be uploaded and stored in a secured data platform, accessible only to permitted Mayo 
Study personnel; additionally, it will be uploaded into the patient’s EPIC EMR. 
No preliminary or final results will be released or published with identifying information or reported on an 
individual level, and all epidemiologic data will be presented as statistical summaries. No statistics will be 
published based on fewer than 5 subjects, a practice consistent with HIPAA and most confidentiality 
guidelines. 
Information about study subjects will be kept confidential and managed according to the requirements of the 
Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those regulations require a signed 
subject authorization informing the subject of the following:  
• 
What protected health information (PHI) will be collected from subjects in this study 
• 
Who will have access to that information and why 
• 
Who will use or disclose that information 
• 
The rights of a research subject to revoke their authorization for use of their PHI.  
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 should be made to obtain permission to collect at least 
vital status (long term survival status that the subject is alive) at the end of their scheduled study period. 
11.1. Institutional Review Board (IRB) Review 
11.2. Informed Consent Forms 
A signed consent form will be obtained from each participant. The consent form will describe the purpose of 

Page 12 of 23 
 
the study, the procedures to be followed, and the risks and benefits of participation. A copy will be given to 
each participant and this fact will be documented in the participant’s record.  
For patients not fluent in English, an interpreter will be present to translate the informed consent and for the 
discussion of the informed consent with the trained study team member. It is already a standard of care at 
Mayo Clinic that all patients considered not fluent enough in English will have interpreter services. Thus this 
study builds and extends on this practice.  
 
11.3. Participant Confidentiality  
The confidentiality of all participants will be maintained according to the Health Insurance Portability and 
Accountability Act (HIPAA), any special data security requirements, and record retention per the sponsor’s 
requirements. 
Any data, specimens, forms, reports, or records that leave the site will be identified only by a participant 
identification number (Participant ID, PID) to maintain confidentiality.  All records will be kept in a locked file 
cabinet.  All computer entry and networking programs will be done using PIDs only. Information will not be 
released without written permission of the participant, except as necessary for monitoring by IRB, the FDA, the 
NIA, and the OHRP. 
11.4. Study Discontinuation  
The study may be discontinued at any time by the IRB, the NIA, the OHRP, the FDA, or other government 
agencies as part of their duties to ensure that research participants are protected.  
12. ETHICAL CONSIDERATIONS 
This study is to be conducted according to United States government regulations and Institutional research 
policies and procedures. 
This protocol and any amendments will be submitted to a properly constituted local Institutional Review Board 
(IRB), in agreement with local legal prescriptions, for formal approval of the study.  The decision of the IRB 
concerning the conduct of the study will be made in writing to the sponsor-investigator before commencement 
of this study. 
All subjects for this study will be provided a consent form describing this study and providing sufficient 
information for subjects to make an informed decision about their participation in this study.  This consent form 
will be submitted with the protocol for review and approval by the IRB for the study.  The formal consent of a 
subject, using the Approved IRB consent form, must be obtained before that subject undergoes any study 
procedure.  The consent form must be signed by the subject himself and the individual obtaining the informed 
consent. 
13. COMMITTEES 
This study will not convene any particular committee such as a Steering Committee or an Executive 
Committee, a Publication Committee, or an Adjudication Committee.  
14. PUBLICATION OF RESEARCH FINDINGS 
Publication of the results of this trial will be governed by the policies and procedures developed by the Steering 
Committee.  Any presentation, abstract, or manuscript will be made available for review by the sponsor and the 
NIA prior to submission.

Page 13 of 23 
 
 
15. REFERENCES 
1. Joynt KE, Orav EJ, Jha AK. Thirty-day readmission rates for Medicare beneficiaries by race and site of 
care. JAMA. 2011;305(7):675-81 
2. Curtis JP, Schreiner G, Wang Y, Chen J, Spertus JA, Rumsfeld JS, Brindis RG, Krumholz HM. All-
cause readmission and repeat revascularization after percutaneous coronary intervention in a cohort of 
medicare patients. J Am Coll Cardiol. 2009;54(10):903-7 
3. Dunlay SM1, Weston SA, Killian JM, Bell MR, Jaffe AS, Roger VL. Thirty-day rehospitalizations after 
acute myocardial infarction: a cohort study. Ann Intern Med. 2012;157(1):11-8 
4. Rosamond WD, Chambless LE, Folsom AR, Cooper LS, Conwill DE, Clegg L, Wang CH, Heiss G. 
Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 
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5. Furman MI, Dauerman HL, Goldberg RJ, Yarzebski J, Lessard D, Gore JM. Twenty-two year (1975 to 
1997) trends in the incidence, in-hospital and long-term case fatality rates from initial Q-wave and non-
Q-wave myocardial infarction: a multi-hospital, community-wide perspective. J Am Coll Cardiol. 
2001;37(6):1571 
6. Rogers WJ, Canto JG, Lambrew CT, Tiefenbrunn AJ, Kinkaid B, Shoultz DA, Frederick PD, Every N. 
Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the US from 
1990 through 1999: the National Registry of Myocardial Infarction 1, 2 and 3. J Am Coll Cardiol. 
2000;36(7):2056 
7. Heidenreich PA, McClellan M. Trends in treatment and outcomes for acute myocardial infarction: 1975-
1995. Am J Med. 2001;110(3):165. 
8. Fang J, Alderman MH. Dissociation of hospitalization and mortality trends for myocardial infarction in 
the United States from 1988 to 1997. Am J Med. 2002;113(3):208. 
9. Velagaleti RS, Pencina MJ, Murabito JM, Wang TJ, Parikh NI, D'Agostino RB, Levy D, Kannel WB, 
Vasan RS. Long-term trends in the incidence of heart failure after myocardial infarction. Circulation. 
2008;118(20):2057 
10. Rogers WJ, Frederick PD, Stoehr E, Canto JG, Ornato JP, Gibson CM, Pollack CV Jr, Gore JM, 
Chandra-Strobos N, Peterson ED, French WJ. Trends in presenting characteristics and hospital 
mortality among patients with ST elevation and non-ST elevation myocardial infarction in the National 
Registry of Myocardial Infarction from 1990 to 2006. Am Heart J. 2008;156(6):1026 
11. Gibson CM, Pride YB, Frederick PD, Pollack CV Jr, Canto JG, Tiefenbrunn AJ, Weaver WD, Lambrew 
CT, French WJ, Peterson ED, Rogers WJ. Trends in reperfusion strategies, door-to-needle and door-
to-balloon times, and in-hospital mortality among patients with ST-segment elevation myocardial 
infarction enrolled in the National Registry of Myocardial Infarction from 1990 to 2006. Am Heart J. 
2008;156(6):1035 
12. Krumholz HM, Wang Y, Chen J, Drye EE, Spertus JA, Ross JS, Curtis JP, Nallamothu BK, Lichtman 
JH, Havranek EP, Masoudi FA, Radford MJ, Han LF, Rapp MT, Straube BM, Normand SL. Reduction 
in acute myocardial infarction mortality in the United States: risk-standardized mortality rates from 
1995-2006. JAMA. 2009;302(7):767 
13. Roe MT, Messenger JC, Weintraub WS, Cannon CP, Fonarow GC, Dai D, Chen AY, Klein LW, 
Masoudi FA, McKay C, Hewitt K, Brindis RG, Peterson ED, Rumsfeld JS. Treatments, trends, and 
outcomes of acute myocardial infarction and percutaneous coronary intervention. J Am Coll Cardiol. 
2010;56(4):254-63 
14. Kannel WB, Cupples LA, D'Agostino RB. Sudden death risk in overt coronary heart disease: the 
Framingham Study. Am Heart J. 1987;113(3):799 
15. Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, Franzosi MG, Geraci E, 
Levantesi G, Maggioni AP, Mantini L, Marfisi RM, Mastrogiuseppe G, Mininni N, Nicolosi GL, Santini M, 
Schweiger C, Tavazzi L, Tognoni G, Tucci C, Valagussa F. Early protection against sudden death by n-
3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the 
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16. Torp-Pedersen C, Køber L. ffect of ACE inhibitor trandolapril on life expectancy of patients with reduced 
left-ventricular function after acute myocardial infarction. Lancet. 1999;354(9172):9 
17. Krumholz HM, Merrill AR, Schone EM, Schreiner GC, Chen J, Bradley EH, Wang Y, Wang Y, Lin Z, 
Straube BM, Rapp MT, Normand SL, Drye EE. Patterns of hospital performance in acute myocardial 
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2009;2:407–413 
18. Ben-Assa E1, Shacham Y, Golovner M, Malov N, Leshem-Rubinow E, Zatelman A, Oren Shamir A, 
Rogowski O, Roth A. Is telemedicine an answer to reducing 30-day readmission rates post-acute 
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19. Roth A, Malov N, Steinberg DM, Yanay Y, Elizur M, Tamari M, Golovner M. Telemedicine for post-
myocardial infarction patients: an observational study. Telemed J E Health. 2009;15(1):24-30 
20. Leshem-Rubinow E, Assa EB, Shacham Y, Zatelman A, Oren-Shamir A, Malov N, Golovner M, Roth A. 
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Health. 2015;21(10):801-7 
 

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APPENDIX B 
DSMP SAMPLE STUDY REPORT OUTLINE  
Study Report Outline 
I. 
Table of Contents 
II. 
Introduction 
A. Summary of Study Status and Issues or Problems 
B. Report Preparation Procedures 
III. 
Study Description 
A. Project Organization Chart, Personnel 
B. Brief Statement of Purpose of Trial 
C. Projected Timetable and Schedule 
D. List of Any Resource Centers 
IV. 
Study Administration 
A. Recruitment Status 
i. Enrollment by Year/Month 
ii. Comparison of Targeted to Actual Enrollment 
B. Retention Status 
i. Overall Subject Status 
ii. Individual Subject Status 
V. 
Study Data Reports/Tables or Figures 
A. General Information 
i. Enrollment (see Appendix B, Table 1) 
ii. Demographic/Baseline Data (see Appendix B, Table 2) 
iii. Subject Status (see Appendix B, Table 3) 
B. Safety Assessment 
i. Treatment Duration for All Subjects (see Appendix B, Table 3) 
ii. AE Data 
a. Overall Listing (see Appendix B, Table 4) 
b. Specific Symptom Listing (see Appendix B, Table 5) 
c. SAE Listing (see Appendix B, Table 6) 
d. Subject Deaths (see Appendix B, Table 7) 
 
 
 
 
 
 
 

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