Modified Application of Cardiac Rehabilitation for Older Adults
Phase: NA
Conditions: Cardiovascular Diseases, Cardiac Rehabilitation, Transition of Care
Sponsor: Daniel Forman, MD

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 1 of 23 
 
PROTOCOL TITLE: 
Modified Application of Cardiac Rehabilitation for Older Adults (MACRO) 
 
 
Principal Investigator 
Daniel E. Forman, MD 
 
 
VERSION NUMBER: 
Version #1 
 
VERSION DATE:  
7/7/2021 
 
 
NCT Number:  
NCT03922529 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 2 of 23 
 
 
 
Table of Contents 
 
1.0      Purpose/Objectives 
     3-4 
2.0 
Background  
 
 
 
 
 
 
 
4 
3.0 
Inclusion and Exclusion Criteria  
 
 
 
 
5 
4.0 
Multi-Site Research  
 
 
 
 
 
 
5 
5.0 
Study Timelines 
 
 
 
 
 
 
 
6 
6.0 
Study Endpoints 
 
 
 
 
 
 
 
6-7 
7.0 
Procedures Involved 
 
 
 
 
 
 
7-15 
8.0 
Data Storage  
 
 
 
 
 
 
 
15-16 
9.0 
Data Management  
 
 
 
 
 
 
16-18 
10.0 Provisions to Monitor the Data to Ensure the Safety of Subjects 
18-19 
11.0 Withdrawal of Subjects 
 
 
 
 
 
 
19 
12.0 Risks to Subjects 
 
 
 
 
 
 
 
19-20 
13.0 Potential Benefits to Subjects 
 
 
 
 
 
20-21 
14.0 Vulnerable Populations 
 
 
 
 
 
 
21 
15.0 Sharing of Results with Subjects  
 
 
 
 
21 
16.0 Setting 
 
 
 
 
 
 
 
 
21 
17.0 Recruitment Methods 
 
 
 
 
 
 
21-22 
18.0 Number of Subjects  
 
 
 
 
 
 
22 
19.0 Provisions to Protect the Privacy Interests of Subjects  
 
22 
20.0 Compensation for Research-Related Injury 
 
 
 
22-23 
21.0 Economic Burden to Subjects 
 
 
 
 
 
23 
22.0 Consent Process 
 
 
 
 
 
 
 
23 
23.0 Process to Document Consent 
 
 
 
 
 
23 
24.0 Drugs or Devices 
 
 
 
 
 
 
 
23 
25.0 
References 
 
 
 
 
 
 
 
 
23-25 
 
 
 
 
 
 
 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 3 of 23 
 
1.0 
Objectives 
 
1.1 Purpose/Objectives. 
 
Cardiac Rehabilitation (CR) is approved for patients with acute myocardial infarction (AMI)/acute 
coronary syndrome (ACS), coronary artery bypass surgery (CABG), percutaneous coronary 
intervention (PCI), stable ischemic heart disease (IHD), heart valve repair (surgical or transcatheter), 
heart failure (HF), and peripheral arterial disease (PAD).1 Yet, participation in CR is low in older adults 
(~13% nationally2), despite their being at greatest risk for harm from the dangers associated with 
cardiovascular disease (CVD) in old age.   
 
Studies on CR participation among older adults cite a lack of systematic referral, delays in starting CR 
following hospitalization, difficulty in finding programs that are convenient and accessible, competing 
time demands from family, and costs of copayments as some of the reasons that CR is poorly utilized.3 
Yet, steps to automate referral, moderate costs, and simplify access have not solved underutilization. 
Further, home-based,4 hybrid,5 and tele-health6 have been promoted as enrichments to CR, but 
adherence in these programs has often been low and the utility of these new formats for older adults 
with complex medical and geriatric challenges remains poorly explored.7 Dr. Daniel Forman developed 
principles and infrastructure for a Modified Application of Cardiac Rehabilitation for Older Adults 
(MACRO) at the VA Pittsburgh Healthcare System (VAPHS) with the effect that participation in CR 
increased from <3% to ~64% (mean age 69 years). MACRO was designed to address the idiosyncratic 
needs of older adults, and to facilitate successful implementation of CR for this population. The goal of 
this trial is to more definitively study the utility of the MACRO intervention. 
 
A key significance of MACRO is the expanded concept of risk. Aging physiology predisposes to CVD 
but also to disablement, multimorbidity, sarcopenia, frailty, cognitive impairment, and sensory 
deficiencies.8 CVD accelerates frailty, disability, and cognitive decline.9 Whereas risk is traditionally 
defined in respect to metrics oriented to the heart and CVD (and standardized as such by the American 
Association of Cardiovascular and Pulmonary Rehabilitation [AACVPR]10), MACRO broadens the 
approach to assessment with additional functional and frailty criteria. In other words, AACVPR criteria 
do not provide a full assessment of risk, since functional risk are distinct, and also predict poor 
cardiovascular outcomes, as well as risks of frailty and disability.7 To address this additional dimension 
of functional risk, the MACRO intervention impacts common geriatric challenges using comprehensive 
risk assessment and coordinated strategies to tailor CR to address these risks.11 
 
Specific Aims/Hypotheses 
 
Aim 1: To establish efficacy, safety and acceptability of the MACRO intervention via a RCT.  
We hypothesize that after 3 months, compared to standard of care (SOC), participants 
randomized into the MACRO arm will have: 
 
H1.1:  Greater improvements in function as measured by Activity Measure for Post-Acute Care 
Computer Adaptive Test (AM-PAC-CAT) Basic Mobility Domain (primary outcome). 
 
H1.2:   Greater improvements in function as measured by accelerometry; AM-PAC CAT Daily 
Activity Domain; depression; frailty; self-efficacy; and quality of life. These will be collected to 
the extent possible in respect to local limitations that may result from fluctuations in COVID-19 
prevalence. 
 
H1.3:  Greater CR participation and adherence. 
 
H1.4:  Greater impact in readmissions and hospitalization.  
 
Aim 2: To examine the duration of benefit of MACRO compared to SOC.  

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 4 of 23 
 
H2.1:  We hypothesize that relative MACRO benefits (i.e., function indices (see H1.2), 
adherence and readmissions/hospitalization will persist after 6 and 12 months (12 
months will be captured as timing allows) 
 
 
 
Aim 3: To explore characteristics of patients who benefit the most from the MACRO intervention. 
H3.1:  We anticipate functional capacity and other baseline characteristics will identify those 
who benefit from the MACRO intervention (exploratory). 
 
2.0 
Background 
 
2.1 Relevant experience. 
Prevalence of cardiovascular disease increases with age. Nonetheless, participation in CR decreases 
with age; only approximately 13% of eligible older patients enroll.2 CR is indicated for patients with 
AMI/ACS, CABG/PCI, stable IHD, heart valve repair (surgical or transcatheter), PAD, and/or HF. 1  
 
Studies on CR participation among older adults cite a lack of systematic referral, delays in starting CR 
following hospitalization, difficulty in finding programs that are convenient and accessible, competing 
time demands from family, and costs of copayments as some of the reasons that CR is poorly utilized.3 
Yet, steps to automate referral, moderate costs, and simplify access have not solved underutilization. 
Further, home-based,4 hybrid,5 and tele-health6 have been promoted as enrichments to CR, but 
adherence in these programs has often been low and the utility of these new formats for older adults 
with complex medical and geriatric challenges remains poorly explored.7  
 
MACRO is a transformational model of care that shifts CR from a primary focus on CVD, to CR that is 
centered on patients themselves, i.e., individuals who usually have many age-related problems in 
addition to CVD. MACRO organizes care relative to patients’ goals of care and composite risks. 
Patients are engaged, assessed for their goals and risks, and education is initiated to best facilitate 
informed choices regarding realistic and practical strategies. Selection of site-, home-, or hybrid-based 
care is based on which option will best meet that individual patient’s preferences and comprehensive 
needs.  
 
2.2 Significance of the research. 
 
A. MACRO is patient-centered CR tailored for older complex patients with CVD. 
A central premise of MACRO is that clinical approaches to older adults with CVD must address 
more than their cardiovascular issues.  MACRO incorporates geriatrics principles in association with 
CV principles as co-dominant priorities of care. 
   
2.3 Innovation of the research.  
 
A.   MACRO responds to a critical gap in CVD management by melding CR principles with geriatric risk 
modifying strategies in an intentional and flexible treatment approach. MACRO is designed to optimize 
accessibility and effectiveness, and to augment the potential for recovery from CVD events that are 
highly prevalent and otherwise prognostically dire. MACRO constitutes an important advance in 
geriatric cardiology wherein the conventional approach to CVD care is transmuted and enriched by 
linking cardiovascular management to the broader complexity of aging. 
 
B.  No prior studies have tested the impact of transitions of care in CR 
 
 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 5 of 23 
 
3.0 
Inclusion and Exclusion Criteria 
 
3.1 Screening for eligibility.  
 
A. Recruitment 
We will randomize approximately 374 participants over approximately 36-months, allowing for a 
conservative 20% dropout to allow for uncertainties in the post-COVID-19 environment.We will 
identify participants using 1) inpatient admission list, 2) referral from providers, 3) CR consults list, 
and 4) approved flyers, letters, and mailings, 5) cardiology consult lists and clinics, and 6) discharge 
list 
 
B. Randomization 
We will use the high quality pseudo-random deviate generator in SAS® (SAS Institute, Inc., Cary, 
North Carolina) to randomize participants to MACRO or SOC in 1:1 ratio with random block sizes 
chosen from small even numbers. Exact block sizes will be revealed to the rest of the study team at 
the conclusion of the study to prevent educated guessing. There are some key demographic 
differences in populations served by the study sites, as described in the Study Settings section. 
Thus, randomization will be stratified by site to ensure a balance between the treatment groups with 
respect to site by design rather than chance. To retain maximum degree of flexibility in post-COVID-
19 environment, no other stratification criterion will be employed. The statistician will create 
schedules which link the randomization sequence number and treatment arm and will provide them 
to the team constructing the data management system. At randomization, a study team member will 
establish the link between the participant study identifier and randomization sequence number by 
clicking on a database function. Randomization data will only be visible to the study statistician and 
intervention delivery personnel. Therefore, all personnel involved in post assessments will be blind 
to treatment assignment.  
 
3.2 
Specific Criteria 
 
Summary of Inclusion criteria: 1) Age ≥70 year; 2) Eligible CVD diagnosis (hospitalization or acute 
event for AMI/ACS, stable CAD, revascularization [CABG, PCI], valvular heart disease [specifically, 
surgical or percutaneous intervention for mitral regurgitation or aortic stenosis], PAD or HF 
[exacerbation or new diagnosis]); 3) English speaking and able to provide informed consent; 4) able to 
be assessed and undergo study interventions. 
 
Summary of exclusion criteria: 1) Unstable medical condition as indicated by history, physical exam, 
and/or laboratory findings; 2) Presence of non-CVD conditions likely to be fatal within 12 months (e.g., 
metastatic cancer); 3) Severe cognitive impairment: Short Blessed with a score of 13 or greater, or 
cannot consent (as indicated by medical record); 4) Long-term care resident at admission with no plans 
to return to independent living; 5) anticipates inability to return for required reassessments. 
 
3.3 Special Populations 
Vulnerable populations (fetuses, pregnant women, children, prisoners, and institutionalized persons) 
and adults unable to consent will not be included in this study. 
 
4.0 
Multi-Site Research 
The University of Pittsburgh will serve as the coordinating site. 
 
 
5.0 
Study Timelines 
 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 6 of 23 
 
• 
Duration of an individual subject’s participation in the study: 
Each participant’s participation in the study will last between approximately 26-52 weeks, 
depending on their time of enrollment into the study. The goal will be for as many 
participants to reach 52 weeks as the time of the study allows. Starting during inpatient 
hospitalization or within 90 days after an acute event and following the participants for 
approximately 26-52 weeks from enrollment.  
 
• 
The duration anticipated to enroll all study subjects: 
We anticipate that we will enroll all study subjects over approximately 24 months. 
 
• 
The estimated date for the investigators to complete this study (complete primary analyses): 
We anticipate that we will complete data collection over approximately 52 months as 
indicated in the study timeline below. 
 
Study Timeline 
 
 
 
 
 
 
 
 
 
 
 
 
 
6.0 
Study Endpoints 
 
6.1 Primary and secondary study endpoints. 
 
All eligible and consenting patients will undergo a standard battery of assessments at baseline and 
after approximately 3, 6, and 12 months (12 months as the study length allows). Assessors will be 
blinded regarding each patient’s group assignment.  
 
Aim 1: to test relative benefits of the MACRO vs. SOC arms, comparing (a) differences in the AM-PAC 
CAT Basic Mobility Domain (primary outcome; primary endpoint 3 months), as well as (b) 
complementary functional/qualitative metrics accelerometry, AM-PAC CAT Daily Activity Scale, 
depression, frailty, self-efficacy, and quality of life); (c) differences in participation, and adherence; (d) 
readmissions and hospitalization. 
 
In Aim 2, assessments in physical activity (accelerometry); AM-PAC CAT Daily Activity Domain; 
depression; frailty; self-efficacy; and quality of life will be repeated at approximately 6 and 12 months 
(12 months as the study length allows) to evaluate longer term impact of the MACRO intervention vs. 
SOC.  
 
In Aim 3, moderator analyses will examine characteristics of patients to identify those most likely to 
benefit from a MACRO intervention. 
 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 7 of 23 
 
7.0 
Procedures Involved 
 
7.1 Study design. 
 
Overview and summary of design: This is a pragmatic randomized controlled trial (RCT) of 374 older 
adults, with 40 subjects at the University of Pittsburgh, eligible for CR: hospitalized adults aged ≥70 
years with a primary diagnosis of AMI/ACS, stable IHD, CABG, PCI, valvular heart disease (valve 
replacements or repairs for aortic stenosis or mitral regurgitation), PAD or HF. Patients who consent to 
participate will be randomly assigned to MACRO or SOC arms (which may include CR at the discretion 
of the providers) (Figure below). In the MACRO arm, patients will benefit from personalized 
engagement and CR will be explicitly facilitated, enhanced, tailored to patients’ preferences and needs, 
and utilizing a flexible range of options (site-, home, or hybrid). In comparison, SOC provides no 
specialized engagement, and no programmatic facilitation, enhancement, customization, or deliberate 
flexibility in how care is provided.   
 
 
 
 
 
 
 
 
 
 
 
IN-HOSPITAL 
AFTER HOSPITAL (3 months) 
LONG-TERM FOLLOW-UP (6-12 mo) 
• Patients’ personal goals 
clarified  
• CR options selected 
(site, home, or hybrid) 
based on composite 
patient preference and 
risk assessment eval 
• MACRO Inpatient/ 
directly post discharge 
Edcuaiton 
• Phone call within week of discharge to review 
plans for phase II outpatient CR  
• Outpatient phase II CR initiated  
• Weekly MACRO phone calls continue re: 
barriers and facilitators for sustained 
participation 
• Engagement techniques throughout phases, 
tailored for older adult 
• Geriatric management: de-prescribing 
medications; nutrition assessment 
• Monthly MACRO phone calls 
continue to engage patient 
and address barriers and 
facilitators to sustained 
behavior change 
MACRO 
n=187 
STANDARD 
n=187 
• Standard of care  as 
determined by care 
team 
• Patient pursues referral for CR 
• Patient presents to outpatient phase II 
outpatient CR, is enrolled in site- or 
home-based model  
• No long-term intervention 
 
Function 
Cognitive function 
Adherence 
Rehospitalization 
Patient self-reports 
3 mo. 6 mo. 
12 mo. 
Baseline 
ASSESSMENT

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 8 of 23 
 
A. Data collection overview 
   
B. Table 1 shows outcome measures planned at each time point. 
 
Table 1.  Data Collection Plan 
 
Study Measure 
Baseline 
3, 6, 12 months  
Risk assessment  
X 
 
AM-PAC CAT Basic Mobility Domain (primary outcome) 
X 
X 
Accelerometer 
X 
X 
AM-PAC CAT Daily Activity Domain 
X 
X 
3 Day Food Record (not at WU site) 
X 
X 
Questionnaires  
X 
X 
CR adherence/attendance  
 
X 
Reduced falls, medication burden, readmissions and hospitalization 
X 
X 
 
 
7.2 Research procedures. 
 
Assessments  
Assessments will occur at some or all of the following time points: baseline (while inpatient or up 
to approximately 90 days following an acute event), and 3, 6, 12 months (12 months as study 
length allows) post-randomization. Assessments can be completed in-person (at facility), by 
telephone or video call.  
Assessments are outlined below:  
 
A. Cognitive function. Short Blessed (score ≥13) will be used as an initial screening tool to rule-out 
severe cognitive impairment. 
 
B. Depression: Patient Health Questionnaire 9-item (PHQ-9). Older adults eligible for CR have high 
rates of depressive symptoms that amplifies vulnerability to disability.12, 13  Mitigating depressive 
symptoms is an important rehabilitation outcome. The PHQ-9 is a simple, pragmatic instrument that 
is well-validated and responsive to change. A score of 10 or greater indicates depression 
symptoms.14  For all patients with PHQ-9 ≥10 who are not receiving treatment for their depression 
already, we will consult Dr. Lenze and also notify their primary provider (as needed) to enable 
follow-up and greater safety. If a participant expresses or demonstrates suicidal ideation, standard 
of policy of the local hospital for suicide risk will also be followed.  
 
C. Readiness for Change: Interventions like CR that require active engagement by participants are 
often dependent on the participant’s willingness to adopt new activities, habits and routines.15 The 
TTM is a behavioral framework for understanding readiness for change through 5 change-stages: 
(1) precontemplation, (2) contemplation, (3) preparation, (4) action, (5) maintenance. In studies 
examining patient-centered interventions with community-dwelling older adults, increased readiness 
for change was associated with a 62% greater likelihood of goal attainment.16  
 
D. AM-PAC-CAT: The AM-PAC is an activity limitations measure.17 This measure is picked as an 
important complement physical assessment measures both as a self-reported index, and because it 
clarifies relative degrees of capacity amidst the heterogeneity anticipated in this population (i.e., frail 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 9 of 23 
 
to robust). AM-PAC allows for the examination of perceived difficulty and level of 
assistance/limitations in 3 domains – Basic Mobility (primary outcome), Daily Activity, and Applied 
Cognition, building on Item Response Theory (IRT).18 AM-PAC- combines items from existing 
instruments into one scale, and ranks them according to level of difficulty for each of the 3 domains. 
IRT assumes that all items within a domain measure a single concept and are independent. In this 
study the Basic Mobility domain will be the primary outcome, and the Daily Activity domain will be 
one of the secondary outcomes. 
 
E. Self-efficacy: Higher self-efficacy correlates to greater capacity and duration for physical activity 
and independence.19-21 For this study we rely on the 13-item self-efficacy scale developed by 
Sullivan, et al.22  
 
F. Quality of Life (QoL):  RAND-12 is a 12-item scale developed to evaluate QOL.  
 
G. Falls: Falls are a common, deleterious, and expensive aspect of aging which may be preventable 
via the tenets of MACRO such as good transitional care, age-appropriate exercise, and de-
prescribing. We will measure falls as follows: at baseline, we will ask, “Have you had any falls in the 
past 3 months?” In follow-up assessments, we will ask about interim falls, as well as their severity 
(e.g., if they caused injury). 
 
H. Deprescribing-Eligible Medications (DEMs):  DEMs are medications that are potentially 
deleterious for participants. These medications are pre-identified, based in part on the Beers 
Criteria23 and in part based on CR-specific risks of falls. 
 
I. Readmissions: At follow-up assessments, we will ascertain whether the participant had any 
hospital admissions or other care (e.g., ER visits). 
 
J. Institutionalization:  At follow-up assessments, we will ascertain whether the participant required a 
brief or long-term institutionalization (e.g., Assisted Living, Skilled Nursing Facility [SNF] or inpatient 
rehabilitation).  
 
 
K. Physical activity.  Physical activity will be measured in all participants at each assessment for 
approximately 7-10 days using the ActiGraph accelerometer.  Participants are asked to wear the 
ActiGraph on their wrist for 7-10 days, removing it only for times when the arm will be submerged in 
water for long periods of time like swimming.  After 7-10 days, participants will mail the 
accelerometer back to the study team in a stamped, pre-addressed envelope provided to them at 
their study visit, or they will bring it with them to their next scheduled visit.  We may also contact 
participants by telephone to ensure monitors are returned.   
 
L. Adherence to the cardiac rehabilitation program.  An assessment of the total number of CR 
sessions participants complete will be tracked via telephone calls, collection of data from the onsite 
cardiac rehabilitation programs, and/or self-report by participants at the completion of the study.  
 
 
M. Risk Assessment. The aggregate risk of each participant will be assessed at baseline. We will 
assess risk across three domains: medical, functional, and psychosocial. An assignment of high, 
moderate, or low risk will be determined using the participants’ scores on various baseline 
assessments.     
 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 10 of 23  
N. Duke Activity Status Index (DASI) is a 12-item scale that has been validated in cardiac patients 
against peak VO2 and has been demonstrated to be a reliable and responsive tool to quantify 
physical activity in daily living.24 
 
O. FRAIL Scale. A five-item scale frailty assessment that assesses Fatigue, Resistance, Ambulation, 
Illnesses, and Loss of weight that can be administered over the phone.25     
 
P. Rapid Estimate of Adult Literacy (REALM-SF).  (optional as now contingent on COVID-19 
risk) Will be utilized to evaluate health literacy on all participants. 
 
Q. Nutrition:  Will be assessed with the Rapid Eating Assessment for Participants short (REAP-S)26 (to 
be collected at all sites) and a 3-day food record (not collected at WU site). REAP-S is a 16-item 
questionnaire to assess eating habits for patients.  A 3-day food record allows will also be collected 
to assess quantities of specific food groups (such as protein).   
 
MACRO Intervention  
 
Early Contact. MACRO study staff will continue to monitor inpatient participants electronic medical record 
charts for consults to PT/OT/CR. Education will be provided over the phone or in person to enhance the 
transition to home and to facilitate transition to outpatient CR. The rationale for CR will be explained and 
the shared decision making between the patient and providers will be emphasized. 
 
Risk Determination. Aggregate risk assessment will be completed on each participant (both MACRO 
intervention and controls) with methods that integrate baseline study indices across three domains: 
medical, functional, and psychosocial. In the MACRO Intervention group only, these risk assessment 
scores will be used as a means to inform coaches of broad patient challenges that need to be addressed 
with CR care, as parts of site-, hybrid- and home-based options. 
 
MACRO Intervention arm transitional care: The MACRO Intervention includes therapeutic 
reinforcements in the days after discharge/enrollment. When feasible, home calls start the week of 
discharge/enrollment, study staff will contact the participant approximately once each week (intent to treat) 
to address questions and to encourage the patient to continue the chosen CR option (site-, home-, or 
hybrid). Phone calls will continue throughout the phase II CR period to help ensure adherence and as 
recovery evolves.  
 
Our methods for maintaining care and observation throughout transitions (including to skilled term nursing 
facility [SNFs] or rehab) were developed at the VAPHS and include (1) Establishing rapport with potential 
participants and their families; (2) Collecting information for several different methods of contact to ensure 
close communication over the duration of the study; (3) Phone calls with participants intermittently while 
they are at SNF or inpatient rehab; (4) sending reminders to the participants and their family members that 
the team will be calling them; (5) Verification of discharge plan at SNF/rehab discharge and confirmation 
that alternate contact information is up-to-date.27 
 
Patients in the MACRO Intervention arm will be encouraged to participate in outpatient phase 2 
Clinical CR (site-, home- or hybrid-based options)  
 
Site-based Clinical CR: MACRO Intervention participants may be enrolled in outpatient site-based CR.  In 
addition to the commitments and benefits of that program, participants will also receive weekly MACRO 
phone calls that reinforce complementary MACRO-based priorities. The emphasis of the calls is to 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 11 of 23  
reinforce the site-based programs, and to also better facilitate the goal of transitioning from site-based CR 
to management the participant can achieve independently at home.. 
 
Home-based Clinical CR: MACRO Intervention participants may be enrolled in home-based CR. While 
home-based CR will vary with each site’s clinical program and even within each program over time, 
minimal standards of home-based CR for MACRO will include at least weekly contact by qualified 
personnel, with implementation of a curriculum that offers requisite components of exercise training, 
education, support, and linkage to dietary consultation when indicated.   
 
In addition to the commitments and benefits of the home-based program, participants in the MACRO 
intervention arm will also receive weekly MACRO phone calls that reinforce complementary MACRO-based 
priorities.  The emphasis of the calls is to reinforce the home-based programs.  
 
Hybrid-based Clinical CR: MACRO Intervention patients may also be enrolled in hybrid-based CR.  
Hybrid CR starts with site-based care, but then transitions to home-based care as the patient and clinicians 
feel suitable. The transition may be triggered by evolving medical stability, growing self-confidence, or other 
factors which impact on each patient’s capacity for home-based CR. The time required for this transition 
will vary between individuals. 
 
In addition to the commitments and benefits of the hybrid program, participants in the MACRO intervention 
arm will also receive weekly MACRO phone calls that reinforce complementary MACRO-based priorities.  
The emphasis of the calls is to reinforce hybrid CR.  
 
Responding to patients’ goals and needs: The MACRO Intervention arm tailors care to each participant 
in two ways, matching care to (1) the participant’s personal preferences as part of Enhanced Medical 
Rehabilitation (EMR) goal setting and motivational; and (2) elements of risk that are detected as part of 
their comprehensive risk profile (that includes medical, physical, and psychosocial domains). The 
underlying premise is that each patient requires a personalized approach to integrate preferences and 
risks. MACRO’s flexibility is an essential aspect of this management. The MACRO intervention, for 
example, emphasizes seated activities for patients with risks of falls. The MACRO intervention also 
organizes family supports, repetitive learning strategies, and community activity resources for participants 
with learning impairments. The MACRO intervention emphasizes strength, balance, and nutrition for 
participants who are frail. 
 
CDC Check for Safety Check list:   
Participants in the MACRO Intervention arm may receive a Home Fall Prevention Checklist for Older 
Adults. This check list will be utilized to provide the participant the opportunity to be better informed about 
safety. The check list may be sent when direct home assessments are not completed. 
 
MACRO De-Prescribing: All participants in MACRO will have their medications reviewed to identify DEMS 
(deprescribing eligible medications).  DEMs worsen functional recovery, impair cognitive function, and 
increase medical risks (falls, bleeding).31 For participants in the MACRO Intervention arm, opportunities for 
de-prescribing will be reviewed and specific recommendations will be conveyed to the participant’s clinician 
to optimize recovery (optimizing physical function, minimizing confusion, reducing falls). 
 
Deprescribing assessments will be conducted during the baseline assessments as part of a medication 
review.  Communication will then be initiated with the MACRO participant’s primary provider. DEMs have 
been selected based on goals to optimize function, reduced sedation, and minimize falls.  
 
If DEMS are deprescribed, a standardized approach of follow-up assessments will be implemented to 
ensure deprescription is well tolerated.  

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 12 of 23  
 
MACRO arm personalized nutrition: Older CVD patients are particularly prone to sarcopenia, frailty, and 
associated vulnerabilities such as exercise intolerance, falls, and poor QOL. A high-quality diet and 
increased protein intake have been shown to be advantageous in these vulnerable adults.￼ The MACRO 
Intervention participants will be strongly encouraged to meet with a registered dietitian and receive dietary 
recommendations that will account for sarcopenia, underweight, overweight, and specific dietary 
restrictions associated with comorbid conditions (e.g., DM, renal disease) and medications. Nutrition 
education and facilitation will be optimized in MACRO. The MACRO Intervention participants will be 
strongly encouraged to meet with a registered dietitian and receive dietary recommendations that will 
account for sarcopenia, underweight, overweight, and specific dietary restrictions associated with comorbid 
conditions (e.g., DM, renal disease) and medications. Nutrition education and facilitation will be optimized 
in MACRO. 
 
MACRO Intervention arm telephone intervention.  MACRO staff will contact participants randomized to 
the MACRO arm approximately once each week until the completion of phase II after which approximately 
monthly phone calls will be completed. A subset of telephone calls will have a second MACRO staff 
member listening to calls to enable additional monitoring.  The components of each session recorded on 
the checklist.  
 
7.3 Quality Assurance  
 
A. Fidelity refers to whether team members consistently perform the MACRO intervention with a high 
level of adherence to and competence with the intervention protocol. Low fidelity is a common and 
often unrecognized problem leading to “failed” intervention studies.33 We will apply expertise from 
numerous intervention studies, including multi-site studies: (1) Attaining fidelity – we will train team 
members at each site. (2) Measuring and maintaining fidelity – Co-investigators will have regular 
supervisory calls with team members. Their intervention sessions may be randomly sampled by the 
supervisors and rated according to meeting fidelity standards. The PIs are the ultimate fidelity 
supervisors; they will be in regular contact with the supervisors, study coordinators, and research 
assistants to promptly detect and correct problems. Such training and monitoring have been successful 
in our recent rehabilitation studies.34 
 
B. Interventionist training and certification. Prior to beginning the study, the research staff will be 
trained on the intervention.  Regular telephone calls will be held with intervention research staff to 
discuss problem participants or challenging issues that arise in the delivery of the intervention.   
 
C. SOC control group.  The SOC group controls for the possibility that regular contact with the study 
team may improve outcomes in participants randomized to the intervention.  Participants randomized to 
the SOC group will follow the standard hospital process and may or may not receive CR.  
  
D. Quality control of outcome measures.  All research study staff will be trained in each aspect of the 
study that they are involved in. Training will be completed by subject matter experts in the specific area 
within the research team. Data will be reviewed for quality control, standardization, and abnormalities in 
collection and will be discussed at regular meetings. 
  
 
7.4 Procedures performed to lessen the probability or magnitude of risks. 
In the event that in-person assessments or interventions become infeasible (e.g., COVID 19 
outbreak), the researchers will carry out these study components remotely (i.e., by telephone, 
mail, email, Redcap, e-consent, or video call. 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 13 of 23  
 
A. Adequacy of protection against risks and methods to minimize potential risks.   
Overview of protection against risks.  Research staff is trained in each element of the study visit they 
will perform; including obtaining informed consent, administering questionnaires, protecting 
confidentiality of collected data, performing the frail assessment. Additional training will be provided as 
needed.    
 
B. Minimizing risks related to assessments.  If a participant develops symptoms such as chest 
discomfort, new dyspnea, new fatigue, study staff will notify hospital or facility staff, or the study 
cardiologist. 
 
C. Staff Training. All research staff will undergo training and certification prior to working with participants 
and will re-certify as necessary every 12 months to ensure continued adherence to study protocol.   
 
D. Minimizing risk related to loss of confidentiality.  The following methods will be employed to 
maintain confidentiality of participants. Research staff members have completed training in the ethical 
conduct of human subject research, including maintaining participant confidentiality.  Only study 
investigators and research staff will have access to the study database.  Participants will be assigned a 
unique study identifier.  Individual names will ultimately be removed from the study database and only 
the unique study identifier will be used to distinguish participants in the database.  Data will be 
maintained in computer files and file cabinets to which only the study staff have access.  Collected data 
will be used only for research purposes.  Any published data will not contain any individual identifiers. 
 
E. Minimizing risk related to loss of confidentiality during intervention.  Participation includes a risk 
of loss of confidentiality regarding personal health information. However, all research staff have 
undergone formal human subjects training.  They are trained to protect the privacy of research subject 
participants.   
 
F. Data and Safety Monitoring Board (DSMB).  The DSMB will meet approximately every six months or 
as decided by the DSMB.  The DSMB will meet to review and approve the protocol prior to beginning 
data collection.  They will decide on specific stopping criteria for the study. The biostatistician and data 
manager will work closely with the DSMB to provide reports in an acceptable format. Serious Adverse 
events (SAE) / Adverse events will be monitored continuously throughout the study and will be reported 
to the DSMB and IRB according to pre-specified requirements.  SAE/AE rates and interim study results 
will be reviewed and discussed by the DSMB at the DSMB meetings.   
 
7.5      Source records that will be used. 
Sources of material.  Primary and secondary outcome measures that will be collected for this study 
include the AM-PAC CAT, accelerometry, cognitive assessment, depression, frailty, IADLs, readiness 
for change, adherence, self-efficacy, falls, medication assessment, readmissions, institutionalization.  
 
 
8.0 
Data Storage 
 
8.1 Data to be stored  
Data at the active sites will be coded; meaning that a key will exist that can link the codes back to 
the direct subject identifiers. Each participant will be assigned a unique study ID number that can 
be traced back to the study participant.  Data provided to the coordinating center will be de-
identified. 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 14 of 23  
 
8.2 Procedures to release data. 
Only the local site PI has control over release of study data.  Any investigators seeking to analyze 
data must contact the site PI for permission.  Each request, if it occurs, will be considered on a 
case-by-case basis and will require obtaining IRB approval prior to releasing. 
 
9.0 
Data Management 
 
9.1 Data analysis plan.  
 
A. Data management.  Data management staff will coordinate the data oversight under the direction 
of Dr. Perera study statistician for all sites and will utilize the insight form the University of 
Pittsburgh Physical Therapy Data Center for Data Management.  
 
B. Data Safety Monitoring Board (DSMB).    
The DSMB will also be expected to meet as needed, but not less than, every six months to provide 
an overall summary status report to the regulatory agencies. An emergency meeting of the DSMB 
may be called at any time by the Chair should participant safety questions or other unanticipated 
problems arise.  
In addition, the DSMB Report addressing the following information will be submitted to the IRB at 
the time of continuing review annually or more often as required: 
• 
A list of the research personnel who participated in the data and safety monitoring.  
• 
The frequency of monitoring that took place during the renewal intervals and/or the dates 
that data and safety monitoring was conducted.  
• 
A summary of cumulative data related to unanticipated problems (including adverse events) 
including a determination of causality and whether the risk to benefit assessment has 
changed.  
• 
If appropriate, a summary of pertinent scientific literature reports, therapeutic developments, 
or results of related studies that may have an impact on the safety of study participants or 
the ethics of the research study.  
• 
A summary of the outcome of reviews conducted to ensure subject privacy and research 
data confidentiality.  
Final conclusions regarding changes to the anticipated benefit-to-risk assessment of the study 
participation and final recommendations related to continuing, changing, or terminating the study. 
 
C. Statistical Analyses. Overview-We will perform all main analysis based on intention-to-treat 
philosophy following the a priori plans outlined below. All statistical analyses will be performed and 
overseen by the study statistician Dr. Perera using SAS® version 9 (SAS Institute, Inc., Cary, North 
Carolina). Participant flow will be summarized using a CONSORT diagram.35 Data will be 
summarized by treatment group and time point as well as baseline to follow-up change using 
appropriate descriptive statistics. First, the baseline participant characteristics will be compared 
between the two arms. Any significant differences will be noted and accounted for as additional 
covariates in the sensitivity analyses. Second, main analyses to address the aims will be performed 
as outlined below. Confirmatory hypothesis testing will be performed using multiple imputation for 
missing data. Third, a set of sensitivity analyses including additional covariates and ignoring 
missing data will be performed to evaluate the robustness of our findings.  

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 15 of 23  
 
Baseline Comparisons-Due to the randomization scheme balanced with respect to study site and 
the large sample size, it is unlikely that other baseline participant characteristics will be significantly 
different between the arms. However, we will control for any participant characteristics that are 
found to be significantly different by including them as additional covariates in the sensitivity 
analyses.  In such an event, we will not alter the primary analytic strategy to preserve its a priori 
nature and predictability. We will use independent samples t-, Wilcoxon rank sum, chi-square and 
Fisher’s exact tests, as appropriate based on distributional properties, and continuous/categorical 
nature of the characteristic being compared.  
 
Aim 1 Analysis-We will fit a series of linear mixed models36 using the SAS® MIXED procedure with 
baseline to follow-up changes in continuous outcomes as the dependent variable; intervention arm 
(MACRO/SOC), follow-up time point (3/6/12 months) and their interaction term as the fixed effects 
of interest; the baseline value of the continuous outcome as a fixed effect covariate; and a 
participant random effect to account for multiple measurements over time from the same 
participant. We will appropriately construct means contrasts to estimate MACRO vs SOC at each 
follow-up time point. The magnitude and statistical significance at α=0.05 of the MACRO vs SOC 
difference at 3 months for AM-PAC CAT Basic Mobility Domain will serve as the formal test of the 
primary hypothesis H1.1. If significant, we will define a meaningful responder as having at least a 
2.60 point improvement in AM-PAC CAT Basic Mobility Domain17 over 3 months, compute 
percentage of responders in both arms, and conclude a number-needed-to-treat (NNT) as the 
reciprocal of the difference in percentages. We will employ the same analytic strategy described 
above for each of our secondary continuous outcomes such as physical activity, depression, frailty, 
self-efficacy and quality of life (H1.2). For the secondary outcomes measured only once at 3 months 
such as participation, adherence and satisfaction (H1.3), we will consider using Wilcoxon rank sum, 
chi-square and Fisher’s exact tests to make between-intervention comparisons, depending on the 
categorical/ordinal/interval nature of the outcomes and their propensity for ill-behaved distributional 
properties. For count outcomes such as falls, number of medications, readmissions and 
hospitalizations in H1.4, we will fit a series of negative binomial regression models37 with the count 
outcome as the dependent variable; exposure time for the counts as an offset; a log link function; 
and intervention arm as the main independent factor of interest; and a marker of history of the 
outcome at baseline as a covariate MACRO vs SOC incident rate ratio and its statistical 
significance will serve as tests of H1.4. 
 
Aim 2 Analysis-In the linear mixed models described above for H1.1 and H1.2, we will examine the 
between-intervention means contrasts at 6- and 12-months. The magnitude and statistical 
significance of the MACRO vs SOC arm differences at 6 and 12 months will serve as the formal test 
of the hypothesis H2.1. 
 
Aim 3 Analysis- We will examine characteristics of patients likely to reap the greatest benefits from 
MACRO compared to SOC arms and will be accomplished through exploratory subgroup analyses. 
We will examine subgroups based on baseline AM-PAC CAT Basic Mobility Scale, frailty status, 
cognitive function, and readiness for change. Specifically, for each subgroup definition considered, 
we will add subgroup and subgroup × intervention group interaction terms to the models used in 
Aims 1 and 2. If the interaction terms are statistically significant, we will make subgroup-specific 
between-intervention comparisons.38 
 
Our second avenue of exploration would be to delineate characteristics of patients most/least likely 
to reap benefits from the MACRO intervention. Specifically, we will only use the data from the 
MACRO arm, and define a meaningful responder as having a 3-month improvement of at least 2.60 
points in AM-PAC CAT Basic Mobility Scale. First, we will compare the baseline characteristics of 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 16 of 23  
responders and non-responders using methods described above. Second, we will fit logistic 
regression models with responder status (yes/no) as the dependent variable, and each of the 
baseline characteristics, one-at-a-time, as the sole independent variable to identify which factors a 
likely to be relevant. Third, we will fit a multivariable logistic regression model with all relevant 
baseline characteristics as independent variables, and a forward selection strategy to potentially 
identify a parsimonious collection of relevant baseline characteristics predictive of likelihood of 
benefit. Finally, to better accommodate non-linear associations and interaction effects among 
baseline characteristics, we will consider a classification tree model or CART.39 
 
Missing Data-The best approach for handling missing data is prevention, and our clinical trials have 
had a low missingness rate. We will clearly document missing data and reasons in the CONSORT 
diagram and compare those with missing data to complete data at the follow-up assessments using 
the same methods outlined under Baseline Comparisons subsection above. We will use methods 
such as multiple imputation which consider the uncertainty involved in imputing missing data.40-42 
Multiple imputation is arguably the best method to account for missing data under the ignorable or 
missing-at-random (MAR) assumption, and mitigates bias even when missing data is non-
ignorable.43 Specifically, we will generate M=5 imputed values for each missing value, analyze the 5 
datasets as though complete, and finally combine the results appropriately so that they reflect the 
uncertainty involved in imputation. SAS® MI and MIANALYZE procedures will be used. Other 
approaches to missing data will also be considered in sensitivity analyses.  
 
Sensitivity Analyses-We will perform sensitivity analyses to examine the robustness of our results 
against various assumptions, such as fitting zero-inflated models44 or using dichotomous (any/none) 
operational definitions and logistic regression models. In addition, if analyses of residuals from the 
linear mixed models show violations of statistical assumptions, we will consider fitting models after 
Box-Cox transforming the continuous variables to make them approximately conform to a normal 
distribution.45  
 
D. Sample Size and Power. 
Sample Size Justification. We base our sample size on published data, published statistical 
methods, and commercially available software (SAS® POWER procedure; SAS Institute, Inc., Cary, 
North Carolina). Between-subject standard deviation of the baseline to follow-up change in the 
primary outcome AM-PAC CAT Basic Mobility Scale is approximately 7.97 in rehabilitation 
outpatients.17 We consider 2.60 points a minimally clinically important difference based on MDC68 17, 
46. We plan to randomize 187+187=374 participants, anticipating 149+149 completers assuming a 
conservative 80% retention rate. We can detect a between treatment arm difference of 2.60 points 
in AM-PAC CAT Basic Mobility Scale with 80% statistical power in a two-tailed test at α=0.05.47-50 
This difference is smaller than the  actual observed changes previously reported, indicating ample 
statistical sensitivity. The logistic regression model proposed in Aim 3 requires a minimum of about 
5-10 events per variable, and assuming a half in the MACRO group responds, we would be able to 
fit a multivariable model with at least 15 variables. Thus, we are confident of the adequacy of 
sample size to address all aims. 
 
9.2 Steps to secure data to maintain confidentiality during storage, use, and 
transmission. 
 
All research staff must complete training in protection of subject privacy and prevention of 
disclosure of identifying information. 
 
All data collection forms are maintained in a secure office space. 
 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 17 of 23  
Our study databases are maintained in locked computer files or on secure hard drives that are 
password protected; to which only authorized staff have access. A study manager must provide 
permission for programmers and research assistants to access study databases. 
 
A study identification number will be assigned to each participant. This identification number will be 
randomly generated and will only be connected to patient identifiers by a master list maintained at 
each site. 
 
9.3 Describe any procedures that will be used for quality control of collected data. 
Quality Control.  All study staff will undergo certification training prior to the beginning of 
the study. Every month data checks will occur to check accuracy of the data collection. 
Additionally, to ensure uniformity of sites there may be site visits and on-site trainings for 
staff.   
 
10.0 
Provisions to Monitor the Data to Ensure the Safety of Subjects 
Serious adverse events (SAE) and Adverse events (AE) will be reported to the DSMB 
following the DSMB charter guidelines. The DSMB will have the ability to stop the study at 
any time if there are concerns about safety. SAE will also be reported to each active site’s 
IRB following the provisions required for that site.  
 
• 
To provide for more complete assessment of the possible impact of COVID-19 on 
MACRO, the unblinded study physician and study coordinator at each site will work 
immediately and directly with the study statistician if they have any concerns that an 
AE/SAE is attributable to COVID-19.  This will prompt an expedited report to the DSMB 
and NIA.  
The AE/SAE SOP will be updated accordingly. 
 
11.0 
Withdrawal of Subjects 
Participants may withdraw from the research at any time. If participants decide to leave the 
research, they should contact the site PI at their active site. 
 
If participants stop being in the research,  data already collected may not be removed from the 
study database. Participant will be asked whether the investigator can collect data from their routine 
medical care. If the subject agrees, this data will be handled the same as research data. 
 
12.0 
Risks to Subjects 
 
12.1 Foreseeable risks 
 
 
A. Risks associated with the MACRO home-based and hybrid-based CR program.    
Participants will be increasing exercise and physical activity. Such activity may be associated with 
muscle soreness, musculoskeletal irritation, shortness of breath, fatigue, light-headedness, chest 
discomfort, or nausea.  Physical activity and exercise may also be associated with an increased risk 
of a cardiovascular event, such as a heart attack, cardiac arrest, dangerous arrhythmia, or stroke. 
However, MACRO participants will always be approved for participation by their personal clinician 
to best ensure they are sufficiently stable and such that risks are minimized. 
 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 18 of 23  
Participants participating in CR (site- hybrid, or home-based models) will not participate in 
progressive exercise until a physician deems it appropriate.   
 
 
B. MACRO intervention 
 
CDC CHECK FOR SAFETY; A Home Fall Prevention Checklist for Older Adults will be mailed to 
participants and education will be provided based on participant questions. If there are concerns 
raised by this the PCP will be contacted and a clinical safety assessment will be requested on the 
participants behalf.  
 
C. Cognitive and depression assessment. The PHQ9 and Short Blessed (screening) assessments. 
Each assessment will be self-completed by participants, and they will have the option to skip 
questions if they feel uncomfortable answering. Additionally, staff will be trained in addressing 
questions and will have direct contact with clinical staff to handle more complex occurrences 
following each hospitals outpatient standard operation procedures for increased behavioral health 
assistance.    
 
D. Risks associated with questionnaire administration.  Participation includes a risk of loss of 
confidentiality regarding personal health information.  However, all research staff have undergone 
formal human subjects training to reduce this risk.  Research staff are trained to protect the privacy 
of research subject participants. Burdens associated with questionnaires may be exacerbated by 
the challenge of administering these tools over the phone.  
 
E. Accelerometry assessment: Participants may wear an ActiGraph which is a watch like device 
that goes on your wrist for 7-10 days there is the small chance it may cause a rash or irritation of 
the skin but no more than wearing a regular watch.  
 
 
12.2 If applicable, indicate which procedures may have risks to the subjects that are 
currently unforeseeable. 
There may be risks that are currently not foreseeable as part of the study assessment and 
intervention. 
 
13.0 
Potential Benefits to Subjects 
 
13.1 The potential benefits that individual subjects may experience from taking part in 
the research.  
 
A. Potential benefits of the proposed research.  Participation in the proposed research may or may 
not provide a direct benefit to participants in this research but will enhance the area of medicine on 
knowledge related to the impact of the intervention at improving patient care. Additionally, this 
research involves an intervention that holds the potential for direct individual benefit. The risk is 
justified by the extent of potential benefit to the involved adults, which includes the possibility of 
improved cardiorespiratory fitness (CRF), efficiency, and PA. These data are important for the rising 
population of older adults who are prone to sedentariness and detrimental health effects.  
 
B. Clinical practice guidelines: Recommends CR for all patients post-acute cardiovascular event, 
however CR is drastically underutilized across the Unitized States and even more so by the growing 
number of older adults. CR is a structured program that provides exercise and education for 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 19 of 23  
reduction of future cardiovascular events, and evidence has shown that CR increases life 
expectancy and decreases long term hospital cost. CR programs often require driving to facilities 
with limited scheduled and costs associated with each visit which can create barriers for many 
patients. Additionally, many patients are not told about the availability of CR or the importance of 
CR is not emphasized at the time of the acute cardiac event.  MACRO directly addresses this issue 
by creating the facilitation to CR program.  
 
C. Importance of knowledge to be gained:  MACRO responds to a critical gap in CVD management 
by marrying CR principles with geriatric risk modifying strategies in an intentional and flexible 
treatment approach that can be generalizable. MACRO is designed to optimize accessibility and 
effectiveness, and to augment the potential for recovery from CVD events that are highly prevalent 
and otherwise prognostically dire. MACRO constitutes an important advance in geriatric cardiology 
wherein the conventional approach to CVD care is transmuted and enriched by linking 
cardiovascular management to the broader complexity of aging. 
 
14.0 
Sharing of Results with Subjects 
Participants will not be provided with any study results unless there is a clinically significant event that 
occurs as part of the research project. 
 
15.0 
Setting 
Visits will be completed in-person while inpatient and outpatient visits will be completed via 
telephone or 
 video call at each of the active sites.   
 
16.0 
Recruitment Methods 
 
16.1 When, where, and how potential subjects will be recruited. 
A. Recruitment methods 
A variety of mechanisms will be used to recruit participants for this protocol. Participants 
eligible for cardiac rehabilitation will be identified from inpatient and outpatient admissions 
by reviewing the electronic medical records, daily admission lists, cardiology consults and 
clinic, direct referrals, pre-operative lists, and discharge lists. Study team recruiter will 
request bedside nurse to ask patient if it is okay to approach and to explain study. Those 
interested in participating further will be provided the study brochure and study contact 
information or the option to complete the initial screening in person. Interested discharged 
patients will be approached after discharge if they are unable to be seen by a study team 
member during their stay. 
B.  Advertisements 
An approved study flier and recruitment brochure will be placed in key places and/or be distributed 
to physician offices, related clinics, or on other occasions/venues that present as an opportunity to 
recruit (e.g., a PI speaking engagement). Potential participants can self-refer by contacting the 
study staff via a telephone number/email address that is provided on these advertisements. With 
subject permission, they will be screened on the phone to make a preliminary assessment of 
eligibility. We will obtain permission to access their medical records in the UPMC database or 
request records from their provider as needed to further document eligibility.  

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 20 of 23  
Advertisement, such as on radio, television, internet or social media, print copy in newspapers, or 
bus signs may also be utilized depending on recruitment rates.  
16.2 Amount, timing, and method of any payments to subjects. 
Subject Reimbursement 
The participant will receive $20 for each of the assessments that s/he undergoes and $10 
per Actigraph return up to $120. If the participant withdraws from the study, s/he may still 
retain payment for the portions of the study that s/he completed. Participants may be 
reimbursed based on mileage.  
17.0 
Number of Subjects 
Recruitment.  
We will randomize approximately 374 participants, approximately 40 at the University of 
Pittsburgh over approximately 24-months, allowing for a 20% drop-out at 52-week follow-up.  
 
18.0 
Provisions to Protect the Privacy Interests of Subjects 
18.1 Steps that will be taken to protect subjects’ privacy interests and to make the 
subjects feel at ease with the research situation. 
Questionnaires and assessments will be administered by telephone calls/video calls 
and/or appropriate space based on the activity by a trained and certified research staff 
member. All information collected as part of the study will be stored in double locked 
locations or on secure access drive in which only study staff have access in accordance 
with each site’s regulation.  Only de-identified data will be provided to coordinating center.   
 
19.0 
Consent Process 
Participants must provide informed consent. The information about this study will be given to the 
subject in language understandable to them. A trained member of the research team will present 
the study. They will verbally present a general outline of the research plan, including inclusion and 
exclusion criteria, to the prospective participant. The consent form, outlining the design of the 
study, will include the risks and benefits of participating, and will be reviewed. The consenting 
member of the research team will answer any questions. Prospective participants may take as 
much time as required to make an informed decision. Written informed consent will be obtained 
from each participant and the research team member prior to performing any research study 
procedures. Site PI or another study investigator are also available to answer any questions that 
participants may have about the research. 
 
Non-English-Speaking Subjects 
Potential participants who do not speak English will not be eligible for study participation. 
 
Subjects who are not yet adults (infants, children, teenagers) 
Children will not be involved in this research. 
 
Cognitively Impaired Adults 
Participants who are cognitively impaired will not be eligible.  
 

 
 
Protocol- Modified Application of Cardiac Rehabilitation (CR) for Older Adults (MACRO) Page 21 of 23  
Consent will be required from all study participants.  
Participants who cannot provide informed consent are not eligible for participation.  
 
20.0 
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