Comprehensive Cardiac Rehabilitation Feasibility After Stroke
Phase: NA
Conditions: Stroke, Ischemic
Sponsor: HealthPartners Institute

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Comprehensive Cardiac Rehabilitation Feasibility After Stroke – CCR FAST  
 
IRB: A18-361 
NCT: 03944668 
 
 
Clinical Study Protocol 
 
Amendment 2 Date: 25 September 2020 
 
 
Sponsor 
Regions Hospital Medical Staff 
 Research, Education and Development (RED) Fund 
 
 
 
 
This study will be conducted in compliance with the protocol, IND regulations and other 
applicable regulatory requirements. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Confidential Information 
No use or disclosure of this document is permitted without prior written authorization from 
HealthPartners Institute 
 
 

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PROTOCOL SIGNATURE PAGE 
 
 
 
 
 
 
 
I have read this protocol and agree to adhere to the requirements. I will provide copies of 
this protocol and pertinent information to the study personnel under my supervision and 
my hospital ethics committee/institutional review board (EC/IRB). I will discuss this 
material with them and ensure they are fully informed regarding the study medication and 
the conduct of the study according to this protocol, applicable law, applicable regulatory 
requirements, general standards of good clinical practice and hospital EC/IRB 
requirements. 
 
 
 
 
 
 
 
 
 
_______________________________________ 
Principal Investigator 
 
 
 
 
____________________ 
Date  
 
 
 

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PROTOCOL AMENDMENT, VERSION 1 
RATIONALE                                                                                  
CCR FAST Protocol has been amended to account for the COVID-19 pandemic, which has 
resulted in increased health and safety concerns for study participants, their caregivers, and 
clinical site staff because of the risks of person-to-person transmission of disease. 
Because of anticipated disruptions in follow-up visits associated with the global   
COVID-19 pandemic, the 6 month visit has been amended. Recently care delivery has 
initiated in-person visits within HealthPartners and Cardiac Rehabilitation in-person 
appointments have resumed. The final 8 study subjects will be completing the 6 month 
study visit in May/June timeline will have the following: 
Specific data points in the protocol, along with a rationale for each change, are 
summarized below: 
 
• 
Complete Cardiac Rehabilitation Visits –in-person visits conducted in align with care 
delivery. 
 
• 
6 Month Final Visit – conduct by phone or video visit. 
 
• 
Quality of Life, Mood and Cognitive Functioning Questionnaires -Questionnaires that 
can be obtained by phone or video visit.  
 
• 
Blood Test –Obtain historical results from medical records so not to require an 
additional in-person visit. 
 
• 
24 Hour Ambulatory Blood Pressure –Not obtained so not to require additional in-
person visits. During all Cardiac Rehabilitation visits blood pressure, heart rate 
are being monitor.  
 
• 
Brain MRI (Magnetic Resonance Imaging) – To be obtained at Neuroscience Center 
Imaging Department --this is the Primary Endpoint for the study. 
 
 
 

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                                                 TABLE OF CONTENTS            
PROTOCOL SYNOPSIS  
1. INTRODUCTION ...................................................................................................................... 8 
2. SUMMARY OF INTERVENTION DESCRIPTION ................................................................ 9 
3. OBJECTIVES ............................................................................................................................. 9 
3.1. PRIMARY OBJECTIVES ............................................................................................................... 9 
3.2. SECONDARY OBJECTIVES .......................................................................................................... 9 
4. STUDY DESIGN...................................................................................................................... 10 
5. PATIENT SELECTION ........................................................................................................... 10 
5.1. INCLUSION CRITERIA .............................................................................................................. 10 
5.2. EXCLUSION CRITERIA ............................................................................................................. 10 
6. STUDY ASSESSMENTS AND PROCEDURES .................................................................... 11 
6.1. STUDY ASSESSMENTS ............................................................................................................. 11 
6.1.1. National Institutes of Health Stroke Scale (NIHSS) ................................................... 11 
6.1.2. Modified Rankin Scale (MRS) .................................................................................... 11 
6.1.3. European Quality of Life Scale (EQ-5D) .................................................................... 11 
6.1.4. Patient Health Questionnaire (PHQ-9) ........................................................................ 11 
6.1.5. Montreal Cognitive Assessment (MoCA) ................................................................... 12 
6.2. PROCEDURES ........................................................................................................................... 12 
6.2.1. Visit 1: Screening/Baseline (Regions Hospital or HealthPartners Neuroscience Center)
 ............................................................................................................................................... 12 
6.2.2. Visit 2: 6-Week Phone Call (From start of cardiac rehabilitation) .............................. 12 
6.2.3. Visit 3: 3-Month Clinic Visit ....................................................................................... 12 
6.2.4. Visit 4: 6-Month MRI and Clinic Visit ....................................................................... 13 
6.3. EARLY WITHDRAWAL ............................................................................................................. 13 
6.4. SAFETY ................................................................................................................................... 13 
6.5. VITAL SIGNS ........................................................................................................................... 13 
6.6. WEIGHT .................................................................................................................................. 14 
6.7. MRI 14 
6.8. LABORATORY SAMPLES .......................................................................................................... 14 
7.  SUBJECT COMPLETION AND WITHDRAWAL ............................................................... 14 
7.1. SUBJECT COMPLETION ............................................................................................................ 14 
7.2. SUBJECT WITHDRAWAL .......................................................................................................... 14 
8.   ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) .......................... 15 

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8.1. DEFINITION OF AE .................................................................................................................. 15 
8.2. DEFINITION OF SAE ................................................................................................................ 15 
8.2.1. Clinical Laboratory Abnormalities and Other Abnormal Assessments as AEs and                    
SAEs ...................................................................................................................................... 15 
8.2.2. Time Period and Frequency of Detecting AEs and SAEs ........................................... 15 
9. DATA ANALYSIS AND STATISTICAL CONSIDERATIONS ........................................... 15 
9.1. 
STATISTICAL ANALYSIS .................................................................................................. 15 
9.2. 
PRELIMINARY ANALYSIS ................................................................................................. 16 
9.3. 
PRIMARY ANALYSIS ........................................................................................................ 16 
9.4. 
SECONDARY ANALYSES .................................................................................................. 16 
9.5. 
STUDY POWER ................................................................................................................ 16 
10.1. REGULATORY AND ETHICAL CONSIDERATIONS .................................................................... 16 
10.2. QUALITY ASSURANCE ........................................................................................................... 16 
10.3. STUDY CLOSURE ................................................................................................................... 17 
10.4. RECORDS RETENTION ........................................................................................................... 17 
10.5. PROVISION OF STUDY RESULTS AND INFORMATION TO INVESTIGATORS ............................... 17 
10.6. DATA MANAGEMENT ............................................................................................................ 17 
11. REFERENCES ....................................................................................................................... 17 
 
 
 
 
 
 
 
 
 
 
 
 
 

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PROTOCOL SYNOPSIS 
PROTOCOL TITLE 
Comprehensive Cardiac Rehabilitation Feasibility After Stroke 
SHORT TITLE  
CCR FAST  
STUDY PHASE 
Enrollment Complete 
STUDY OBJECTIVES AND PURPOSE  
Study Purpose  
The purpose of this study is to demonstrate the feasibility and safety of including stroke 
patients in a comprehensive cardiac rehabilitation (CCR) program, while examining the 
clinical value in reducing stroke recurrence, myocardial infarction, readmission, and 
mortality in stroke patients. 
Primary Objective  
• To assess the feasibility of comprehensive cardiac rehabilitation for stroke patients. 
Secondary Objective (s) 
• To explore the potential benefits of cardiac rehabilitation for stroke patients by 
describing the 6-month rates of recurrent stroke, myocardial infarction, hospital 
readmission for a cardiovascular or cerebrovascular indication, silent stroke on MRI 
and death. 
STUDY DESIGN  
Study Type Feasibility 
Study Indication Type Intervention 
 
Study Design This study is a prospective feasibility study, which will consist of a 
single arm of ischemic stroke patients. Seventeen patients will be 
consented through rolling recruitment to participate in a 36-session CCR 
program over 12-week period at Regions Hospital Outpatient Cardiac 
Rehabilitation facility. Participants will join the existing cardiac 
rehabilitation program, and undergo the same types of exercise therapy 
and education as the cardiac patients, with slight modifications to the 
educational material to include brain pathology. The primary endpoint 
of the study is the successful completion of the study protocol, which 
consists of attending 75% of the CCR sessions, completing brain MRI 
and laboratory tests at the end of the study, and attending the end of 
study visit. 
Baseline data will be collected while patients are admitted at Regions 
Hospital. If patients need more time to recover, baseline visits will take 
place at HealthPartners Neuroscience Center within 3 months from the 
time of stroke. CCR sessions will also begin within 3 months after the 
patient’s admission for ischemic stroke. The research staff will conduct 
a 6-week phone call (6-weeks after beginning CCR) to determine if any 
adverse events (AE) or serious adverse events (SAE) have occurred and 
to obtain and updated medication list. The 3-month and 6-month clinic 
visits will take place at the Neuroscience Center and will be 3 months 
and 6 months from the date of the baseline visit. Patients will meet with 
Dr. Haitham Hussein and the research staff. The patients’ vitals will be 

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taken and standard assessments (described below) will be performed, 
which are typically performed as standard of care. The 6-month clinic 
visit will also include laboratory tests and a MRI. 24-hour ambulatory 
blood pressure will be monitored and recorded at baseline and at 6-
months. The chart below includes the visit schedule and data collection 
information. 
Planned Duration of 
Subject Participation  
The duration of study participation for each subject is anticipated to be 6 
months from baseline. 
OUTCOMES  
Primary- 
Completion rate  
• CCR sessions 
• 6-month study visit, MRI and labs 
Secondary- 
Benefit 
• 6-month rates of recurrent stroke, 
myocardial infarction, hospital readmission 
for a cardiovascular or cerebrovascular 
indication, silent stroke on MRI and death. 
• Beginning and end comparison of weight, 
BMI, blood pressure, and laboratory values 
SUBJECT SELECTION 
Targeted Accrual 
For this study, we will enroll 17 eligible ischemic stroke patients. We 
will continue to recruit patients until the 17th patient is enrolled in CCR. 
Inclusion Criteria 
• Age ≥ 18 years 
• Patient has suffered an ischemic stroke 
• Patient should be ambulatory (non-disabling stroke) to be able to participate in the CCR 
exercise program 
• Patient is able to start cardiac rehabilitation within 3 months of stroke 
Exclusion Criteria 
• No baseline (index admission for ischemic stroke) MRI completed 
• Life expectancy < 1-year 
• Presence of brain hemorrhage: intracerebral hemorrhage, subarachnoid hemorrhage, 
subdural hematoma, or epidural hematoma  
• Concurrent diagnosis of seizure disorder  
• Patient with moderate or severe neurologic deficits, limiting their ability to participate in 
the CCR exercise program  
• Cardiopulmonary conditions preventing the patient from participation, such as severe 
heart failure, severe aortic stenosis, and exercise-induced asthma 
• Patient with cognitive dysfunction impairing their ability to follow directions 
• Anticipated procedures such as carotid stenting, carotid endarterectomy, and intracranial 
aneurysm coiling 
• Patient unable to commit to the frequent visits of the CCR program  
• Participation in other interventional research (observational research is allowed) 
• Unable to have brain MRI 
• Non-English speaker 
• 
Pregnant women  

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1. INTRODUCTION 
 
There is a significant overlap in risk factors (e.g. hyperlipidemia, hypertension, smoking, 
diabetes, obesity, and a sedentary lifestyle) between ischemic stroke and coronary artery 
disease.1-4 These risk factors contribute to the development and progression of atherosclerosis, 
which is a major cause of ischemic stroke and coronary artery disease. This is why prevention 
strategies for coronary artery disease and stroke are similar.  
 
Comprehensive cardiac rehabilitation (CCR) is standard-of-care after myocardial infarction, 
which includes aerobic exercise, education/counseling, and medication compliance oversight. 
CCR has been shown to improve vascular risk factor control and survival rates, as well as reduce 
re-infarction and hospital readmission rates.5-10 CCR has become an integral part of care for 
many cardiac and pulmonary diseases and is reimbursable by insurance companies. As for 
stroke, only a few studies have examined the use of CCR and these studies focused on assessing 
the impact of the program on risk factors control such as cholesterol level, blood pressure, and 
exercise endurance. No studies examined the impact of CCR on clinical endpoint in stroke 
patients, such as stroke recurrence, readmission, occurrence of other vascular events, and death. 
Due to this lack of evidence, CCR is not reimbursable for a stroke diagnosis.  
 
The standard of care after stroke, revolves around restoring the functions lost by stroke through 
engaging in physical, occupational, and speech therapies. This is a fundamental philosophical 
difference between CCR and stroke rehabilitation. The former aims to improve wellness and 
bring the patient to a healthier state compared to baseline, while the latter aims to bring the 
patient back to baseline. Another important difference between CCR and stroke rehabilitation is 
the extent and intensity of patient education; while there is an education curriculum for CCR, 
stroke patients’ education typically involves a discussion with providers during hospitalization or 
clinic visits counsel regarding risk factors. Coaching provided by the CCR program (e.g. helping 
patients implement a healthier lifestyle and ensuring medication compliance) is lacking in post-
stroke care.  
 
A few studies have attempted to integrate CCR after stroke. These studies showed that CCR has 
short-term beneficial effect on vascular risk factors control (blood pressure, lipid profile, body 
mass index) and exercise endurance.11,12 However, none of these studies specifically evaluated 
the effect that CCR has on clinical endpoints such as stroke recurrence and hospital readmission. 
 
The overall goal of this study is to assess the feasibility of stroke patient participation in Regions 
Hospital’s CCR program. Our study will examine the ability of stroke patient to complete the 
current CCR program (provided as standard of care by cardiology department). The program 
consists of 3 sessions per week over 12 weeks. Exploratory endpoints will be the event rate of 
recurrent stroke at 6 months, MI, death, hospital readmission for a cardiovascular or 
cerebrovascular indication, and silent stroke on MRI. These analyses will help us with our future 
power analysis for a subsequent larger trial. The experience, workflow, and the knowledge 
gained from this study will be used to design a larger study, comparing CCR with conventional 
post-stroke treatment. 
 

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2. SUMMARY OF INTERVENTION DESCRIPTION 
For the study intervention, all patients will be prescribed 36 sessions of comprehensive cardiac 
rehabilitation, which will occur over 12 weeks. Participants will attend the standard of care 
ongoing cardiac rehabilitation sessions at Regions Hospital Outpatient Cardiac Rehabilitation 
facility at 2575 University Ave. in St. Paul, MN. The cardiac rehabilitation program is staffed by 
exercise physiologists, registered dieticians, and registered nurses, under the direction of a 
cardiologist. The cardiac rehabilitation program includes supervised exercise, nutritional 
counseling, medication review, and patient education. Stroke patients will receive the same 
education sessions as the cardiac patients, except for three sessions. Because there were three 
sessions that were specific to cardiac patients (and therefore not relevant to stroke patients), these 
sessions will be replaced with three stroke specific education sessions, which were developed by 
Dr. Haitham Hussein. 
Each session will last approximately 60-90 minutes, and include 30-40 minutes of aerobic 
exercise, 15 minutes of strength training, and a 30 minutes group education session. Patients will 
be instructed to exercise at a rate of perceived exertion of 11-13 on the Borg scale, corresponding 
to “fairly light” to “somewhat hard”.13  Exercise intensity will be increased 0.5-1 metabolic 
equivalent every 1-3 weeks according to patient exercise training parameters. There are 16 
educational modules that will be presented to the patients at the group education sessions. The 
educational material will be modified to include brain pathology.  
At the initial CCR visit, an ambulatory blood pressure monitor will be placed on and sent home 
with the patient. The patient will be monitored for 24 hours and asked to return to the outpatient 
cardiac rehabilitation facility the next day to return the monitor. 
If a patient drops out of the study or stops attending CCR classes, the research staff will call the 
patient to ask why he or she stopped attending CCR. If the research staff is unable to reach the 
patient after two phone call attempts, they will attempt to reach the patient at his or her next 
Neuroscience Center clinic visit to obtain a drop out reason. In addition, adverse or serious 
adverse events will be monitored by the study staff throughout the study. 
3. OBJECTIVES 
3.1. Primary Objectives 
To assess the feasibility of comprehensive cardiac rehabilitation for stroke patients. 
3.2. Secondary Objectives 
To explore the potential benefits of cardiac rehabilitation for stroke patients by describing the 6-
month rates of recurrent stroke, myocardial infraction, hospital readmission for cardiovascular or 
cerebrovascular indication, silent stroke on MRI and death. 
 
 
 
 

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4. STUDY DESIGN 
 
This study is a prospective feasibility study, which will consist of a single arm of ischemic stroke 
patients. Seventeen patients will be consented through rolling recruitment to participate in a 36-
session CCR program over 12-week period at Regions Hospital Outpatient Cardiac 
Rehabilitation facility. Participants will join the existing cardiac rehabilitation program, and 
undergo the same types of exercise therapy and education as the cardiac patients, with slight 
modifications to the educational material to include brain pathology. The primary endpoint of the 
study is the successful completion of the study protocol, which consists of attending 75% of the 
CCR sessions, completing brain MRI and laboratory tests at the end of the study, and attending 
the end of study visit. 
 
Baseline data will be collected while patients are admitted at Regions Hospital. If patients need 
more time to recover, baseline visits will take place at HealthPartners Neuroscience Center 
within 3 months from the time of stroke. CCR sessions will also begin within 3 months after the 
patient’s admission for ischemic stroke. The research staff will conduct a 6-week phone call (6-
weeks after beginning CCR) to determine if any adverse events (AE) or serious adverse events 
(SAE) have occurred and to obtain and updated medication list. The 3-month and 6-month clinic 
visits will take place at the Neuroscience Center and will be 3 months and 6 months from the 
date of the baseline visit. Patients will meet with Dr. Haitham Hussein and the research staff. 
The patients’ vitals will be taken and standard assessments (described below) will be performed, 
which are typically performed as standard of care. The 6-month clinic visit will also include 
laboratory tests and a MRI. 24-hour ambulatory blood pressure will be monitored and recorded 
at baseline and at 6-months. The chart below includes the visit schedule and data collection 
information.    
5. PATIENT SELECTION 
5.1. Inclusion Criteria 
All ischemic stroke patients admitted to Regions Hospital within the study period will be 
identified. 
• Age ≥ 18 years 
• Patient has suffered an ischemic stroke 
• Patient should be ambulatory (non-disabling stroke) to be able to participate in the CCR 
exercise program 
• Patient is able to start cardiac rehabilitation within 3 months of stroke 
5.2. Exclusion Criteria 
A subject will not be included for consideration in this study if any of the following criteria are 
met: 
• No baseline (index admission for ischemic stroke) MRI completed 
• Life expectancy < 1-year 

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• Presence of brain hemorrhage: intracerebral hemorrhage, subarachnoid hemorrhage, 
subdural hematoma, or epidural hematoma  
• Concurrent diagnosis of seizure disorder  
• Patient with moderate or severe neurologic deficits, limiting their ability to participate in 
the CCR exercise program  
• Cardiopulmonary conditions preventing the patient from participation, such as severe 
heart failure, severe aortic stenosis, and exercise-induced asthma 
• Patient with cognitive dysfunction impairing their ability to follow directions 
• Anticipated procedures such as carotid stenting, carotid endarterectomy, and intracranial 
aneurysm coiling 
• Patient unable to commit to the frequent visits of the CCR program  
• Participation in other interventional research (observational research is allowed) 
• Unable to have brain MRI 
• Non-English speaker 
• Pregnant women 
6. STUDY ASSESSMENTS AND PROCEDURES 
6.1. Study Assessments 
6.1.1. National Institutes of Health Stroke Scale (NIHSS) 
NIHSS is a tool used to evaluate stroke severity.14,15 The total score ranges from 0-42, with a 
higher stroke indicating a more severe stroke. 
6.1.2. Modified Rankin Scale (MRS) 
MRS is a tool used to evaluate the level of disability after stroke.16 The assessment ranges from 
0-6, where 0 is no symptoms at all and 6 is dead. 
6.1.3. European Quality of Life Scale (EQ-5D) 
The EQ-5D is a tool used to measure health-related quality of life.17 The tool includes the 
following dimensions: mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression. The scale ranges from 5-25, with 5 indicating no problems and 25 indicating 
extreme problems.  
6.1.4. Patient Health Questionnaire (PHQ-9) 
The PhQ-9 is a tool used to assess depression severity.18 The scale ranges from 1-27, with a 
score of 1-4 indicating minimal depression and a score of 20-27 indicating severe depression. 
 

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6.1.5. Montreal Cognitive Assessment (MoCA) 
The MoCA is a brief cognitive screening tool for detecting cognitive impairment or dementia.19 
The assessment measures multiple cognitive domains including attention, concentration, 
executive function, memory, language, visuoconstructional skills, conceptual thinking, 
calculations, and orientation. The scale ranges from 0-30, with a lower score indicating worse 
cognitive function. 
 
Because the MoCA is assessed three times within 6-7 months, we plan to use different versions 
to reduce the possibility of a learning effect. Occupational therapy completes a MoCA 
assessment during inpatient stroke admission and utilizes version 7.1, so the MoCA score will be 
extracted from the patient’s chart. For the 3-month clinic assessment we will use version 7.2 and 
for the 6-month clinic assessment we will use version 7.3. These are standardized approved 
versions. 
6.2. Procedures 
6.2.1. Visit 1: Screening/Baseline (Regions Hospital or HealthPartners Neuroscience 
Center) 
• Obtain written informed consent from subject (or subject’s legally authorized representative) 
prior to any study related procedures. 
• Review Inclusion/Exclusion criteria. 
• Review medical history, as it pertains to inclusion/exclusion criteria, such as research 
diagnosis, disease severity, and course of stroke. 
• Obtain demographic information.  
• Obtain details of medications.  
• Collect vital signs; heart rate, blood pressure, oxygen saturation, height, and weight. 
• Obtain NIHSS score.  
• Obtain MRS score. 
• Administer MoCA if not previously measured. 
• Administer PHQ-9. 
• Retrospectively collect medical information on laboratory tests, vascular imaging, MRI, and 
echocardiogram. 
6.2.2. Visit 2: 6-Week Phone Call (From start of cardiac rehabilitation) 
• Gather information on cardiac rehabilitation progress. 
• Review current medications.  
• Record AEs/SAEs. 
• 3-month clinic visit will be scheduled 3-months since start of cardiac rehabilitation. 
6.2.3. Visit 3: 3-Month Clinic Visit  
• Collect vital signs.  
• Review current medications. 

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• Administer MoCA. 
• Complete EQ-5D. 
• Complete PHQ-9. 
• Obtain NIHSS score with physician. 
• Obtain MRS score with physician. 
• Record AEs/SAEs. 
• 6-month MRI and clinic visit will be scheduled 6-months since start of cardiac rehabilitation. 
6.2.4. Visit 4: 6-Month MRI and Clinic Visit 
• Undergo MRI. 
• Collect laboratory samples; lipid panel, basic metabolic panel, coagulation panel, 
glycosylated hemoglobin, and Cotinine. 
• Collect vital signs. 
• Review current medications. 
• Administer MoCA. 
• Complete EQ-5D. 
• Complete PHQ-9. 
• Obtain NIHSS score with physician. 
• Obtain MRS score with physician. 
• Record AEs/SAEs. 
 
*This visit may be separated into 2 visits, if needed. 
6.3. Early Withdrawal 
If a patient drops out of the study or stops attending CCR classes, the research staff will call the 
patient to ask why he or she stopped attending CCR. If the research staff is unable to reach the 
patient after two phone call attempts, they will attempt to reach the patient at his or her next 
Neuroscience Center clinic visit to obtain a drop out reason. In addition, adverse or serious 
adverse events will be monitored by the study staff throughout the study. 
6.4. Safety 
 
For all safety assessments described below, any clinically significant change will be recorded as 
an AE or SAE. 
6.5. Vital Signs 
 
Vital signs and O2 saturation will be recorded at visits 1, 3, and 4 and recorded prior to the MRI 
and blood draw.  For within subject consistency, brachial artery pressure will be obtained in the 
routine fashion and the same arm will be used for all study measurements.  
Blood pressure and heart rate will be measured after subject has been sitting quietly for a 
minimum of 5 minutes. Vitals signs and O2 saturation will be monitored by clinical staff during 
each visit of the study. 

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6.6. Weight 
 
Body weight will be measured at visits 1, 3, and 4, without heavy outer clothing or footwear.  
6.7. MRI 
 
A standard MRI will be performed on all subjects at visit 4. This will be performed prior to the 
clinic visit. 
6.8. Laboratory Samples 
 
During visit 4, participant will undergo a blood draw. The following laboratory tests will be 
performed: lipid panel, basic metabolic panel, coagulation panel, and glycosylated hemoglobin. 
Any abnormal laboratory results at this visit will be communicated by the Principal Investigator 
or study staff to the physician and the patient. This can be obtained before or after MRI and 
clinic evaluations. 
7.  SUBJECT COMPLETION AND WITHDRAWAL 
7.1. Subject Completion 
Subjects completing all 3 study visits and 75% attendance of CCR sessions will be considered to 
have completed study. 
7.2. Subject Withdrawal 
 
Subjects may withdraw from study at any time for any reason without penalty or be terminated 
from the study by the clinical investigator (see provisions for termination by study team.) The 
investigational team will document the reason(s) for withdrawal.  In the event a subject chooses 
to withdraw from study before Visit 4, the safety procedures described in Section 6.2.4. will be 
collected within 14 days following subject’s decision to withdraw.  For all subjects who 
withdraw, all final safety assessments will be collected regardless of time elapsed since the 
previous visit.  In addition to final visit, subjects who withdraw early will be contacted within 7 
days by study staff via telephone to assess for the development of any new and/or ongoing AEs 
and concomitant medications.  Efforts will be made to recruit subjects to replace any 
withdrawals so as to maintain an n=17. 
 
Subject’s participation may be terminated at the discretion of the investigator.  Individuals may 
be withdrawn for the following reasons: 
• Clinically significant adverse events 
• Lost to follow-up 
• Protocol violations 
• Inability to tolerate study intervention 
• Other 
 

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8.   ADVERSE EVENTS (AE) AND SERIOUS ADVERSE EVENTS (SAE) 
8.1. Definition of AE 
 
An adverse event is any symptom, sign, illness or experience which develops or worsens in 
severity during the course of the study. Interval development of illnesses or injuries will be 
regarded as adverse events. Abnormal results of diagnostic procedures are considered to be 
adverse events if the abnormality: 
• Results in study withdrawal  
• Is associated with clinical signs or symptoms  
• Leads to treatment or to further diagnostic tests 
• Is considered by the investigator to be of clinical significance 
8.2. Definition of SAE 
 
Adverse events are classified as either serious or non-serious. A serious adverse event is any 
event that results in: 
• Death 
• Life-threatening situation  
• Hospitalization or prolongation of hospitalization  
• Disability or incapacitation  
• Other events determined by investigator to be medically significant in which subject’s well-
being is jeopardized (e.g. events that have high likelihood of escalating to the point of 
meeting criteria outlined above)  
8.2.1. Clinical Laboratory Abnormalities and Other Abnormal Assessments as AEs and                    
SAEs 
Any new abnormal, vital, examination, or laboratory finding judged clinically significant by the 
investigator will be documented as an AE or SAE, if meeting the definitions for such.  Abnormal 
lab findings or other abnormal assessments associated with the disease under study will not be 
considered AEs or SAEs unless more severe than expected, as judged by the investigator. 
8.2.2. Time Period and Frequency of Detecting AEs and SAEs 
Upon consenting, a subject is considered to be a participant in the study, and until that person 
either withdraws or completes study, AEs and SAEs will be recorded.  The investigational team 
will promptly report any AE/SAE as required per federal guidelines. 
9. DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Analysis 
The statistical analysis plan was written by Lauren O. Erickson, Biostatistician at the 
HealthPartners Institute. She will also perform the statistical analyses for the study. 

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9.2. 
Preliminary Analysis  
Descriptive statistics, such as mean and standard deviation (for continuous variables) and 
frequency (for categorical and binary variables) will be computed for all demographic variables. 
Population demographics will include age, gender, stroke type, labs, BMI, and others.  
No imputation for missing data or adjustment for multiple comparisons will be done as they were 
deemed too conservative for this feasibility study. All statistical analyses will be performed in 
SAS 9.4 with p<0.05 considered to be statistically significant.  
9.3. 
Primary Analysis 
The primary goal of this feasibility study will be to determine the study completion rate. This 
will be defined as 75% attendance at CCR sessions, acquisition of 6-month MRI and labs, and 
attendance of end of study visit. We will calculate and report the 95% confidence interval for this 
rate. We will also report the number of charts reviewed, the number of patients screened for 
inclusion/exclusion criteria, the number of patients contacted for the study, the number of 
patients that agreed to participate, the number of patients that started CCR, and the number of 
patients that dropped out or completed CCR. We will also describe reasons for non-completion.  
9.4. 
Secondary Analyses 
For the secondary analyses, we will explore the potential benefits of cardiac rehabilitation for 
stroke patients by describing the 6-month rates of recurrent stroke, myocardial infarction, 
hospital readmission for a cardiovascular or cerebrovascular indication, silent stroke on MRI and 
death. We will assess the individual and composite event rates by calculating the mean and 95% 
confidence interval. This will provide information to allow us to power a larger study. 
Additionally, we plan to descriptively compare weight, BMI, blood pressure, and laboratory 
values at the beginning and end of the study. We will do this by calculating the mean and 95% 
confidence intervals for these values.  
9.5. 
Study Power 
 
Our sample size is based on the capacity of the CCR course as deemed by the cardiac 
rehabilitation program. With a sample size of 17, we will be able to estimate a completion rate of 
75% to within a 95% confidence interval of ± 20.2%. 
 
10. STUDY CONDUCT CONSIDERATIONS 
10.1. Regulatory and Ethical Considerations 
The study will be conducted in accordance with GCP guidelines. Subject privacy requirements 
will be observed, as well as the fundamental concepts of the Declaration of Helsinki (e.g. IRB 
approval of the study, obtaining informed consent from all subjects and meeting all reporting 
requirements). 
10.2. Quality Assurance 
 

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In the event of a regulatory agency audit or inspection, the site will allow the auditor/inspector 
access to all records documented and facilities utilized in conducting the study.  The site will 
also make accommodations (e.g. time, schedule) to discuss findings, concerns, and questions 
with auditor/inspector.   
10.3. Study Closure 
 
Upon completion of all subject visits, data entry and analysis, the investigator will inform the 
local IRB of study closure.  
10.4. Records Retention 
 
All site records will be maintained and stored in a safe and secure location for a minimum of 15 
years post study completion.  
10.5. Provision of Study Results and Information to Investigators 
 
The study results will be made available by the study statistician once the analysis is complete. 
10.6. Data Management 
 
Data collection and reporting tools will be developed and stored internally (e.g. Case Report 
Forms and source documents [Paper/REDCap]). Data collected and stored electronically will 
remain confidential and secure (e.g. secured server and password protected files [REDCap]). 
Study binders will be stored in a locked file cabinet within a locked office. After the study is 
closed, all subject identifiers will be destroyed. 
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