Controlling Hypertension Through Education and Coaching in Kidney Disease
Phase: NA
Conditions: Chronic Kidney Diseases, Chronic Disease, Chronic Kidney Disease, Stage 3 (Moderate), Chronic Kidney Disease, Stage 4 (Severe), Chronic Kidney Disease Stage 5, Hypertension
Sponsor: University of Michigan

 
 
Controlling Hypertension through Education and 
Coaching in Kidney Disease (CHECK-D) 
Protocol Number: HUM00136011 
A related sub-project to: “Quality Improvement and Evaluation of the 
Integration of a CKD Education Tool in a Primary Care Clinic” (HUM00152989, 
unregulated)  
National Clinical Trial (NCT) Identified Number: NCT04087798 
Principal Investigator: Julie Wright, MD, MPH 
Funded by: NIH, National Institute of Diabetes and Digestive and Kidney 
Diseases 
Version Number: v.2.0 
February 3, 2026  
 
 
Summary of Changes from Previous Version: 
Affected Section(s) 
Summary of Revisions Made 
Rationale 
10.5 Appendices 
Update Appendix 1: 
Outcome Measures 
Clarify that the zipcode data includes patients’ home and 
clinic 5-digit zipcodes. The intent is to use both for 
analysis. 
1.1 Synopsis 
1.3 Schedule of 
Activities (SoA) 
Expand Acronym and 
Abbreviation 
Expand acronyms and abbreviations (and include the 
acronyms in parentheses) the first time they are used in 
the protocol. 

  
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Table of Contents 
STATEMENT OF COMPLIANCE ............................................................................................................................. 1 
1 
PROTOCOL SUMMARY ............................................................................................................................... 1 
1.1 
Synopsis ................................................................................................................................................ 1 
1.2 
Schema ................................................................................................................................................. 3 
1.3 
Schedule of Activities (SoA) ............................................................................................................... 4 
2 
INTRODUCTION ............................................................................................................................................ 4 
2.1 
Study Rationale .................................................................................................................................... 4 
2.2 
Background........................................................................................................................................... 5 
2.3 
Risk/Benefit Assessment .................................................................................................................... 8 
2.3.1 
Known Potential Risks ..................................................................................................... 8 
2.3.2 
Known Potential Benefits ................................................................................................ 8 
2.3.3 
Assessment of Potential Risks and Benefits ................................................................ 8 
3 
OBJECTIVES AND ENDPOINTS ................................................................................................................ 8 
4 
STUDY DESIGN ........................................................................................................................................... 10 
4.1 
Overall Design .................................................................................................................................... 10 
4.2 
Scientific Rationale for Study Design.............................................................................................. 11 
4.3 
Justification for Dose ......................................................................................................................... 11 
4.4 
End of Study Definition ..................................................................................................................... 11 
5 
STUDY POPULATION ................................................................................................................................ 11 
5.1 
Inclusion Criteria ................................................................................................................................ 11 
5.2 
Exclusion Criteria ............................................................................................................................... 12 
5.3 
Lifestyle Considerations .................................................................................................................... 12 
5.4 
Screen Failures .................................................................................................................................. 12 
5.5 
Strategies for Recruitment and Retention ...................................................................................... 13 
5.6            Additional Subgroup ................................................................................................................................ 14    
6 
STUDY INTERVENTION ............................................................................................................................ 14 
6.1 
Study Intervention(s) Administration ............................................................................................... 14 
6.1.1 
Study Intervention Description ..................................................................................... 14 
6.1.2 
Dosing and Administration ............................................................................................ 15 
6.2 
Preparation/Handling/Storage/Accountability ................................................................................ 15 
6.2.1 
Acquisition and accountability ...................................................................................... 15 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ................................................ 15 
6.2.3 
Product Storage and Stability ....................................................................................... 15 
6.2.4 
Preparation ...................................................................................................................... 15 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................... 15 
6.4 
Study Intervention Compliance ........................................................................................................ 16 
6.5 
Concomitant Therapy ........................................................................................................................ 18 
6.5.1 
Rescue Medicine ............................................................................................................ 18 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .................................................................................................................... 18 
7.1 
Discontinuation of Study Intervention ............................................................................................. 18 
7.2 
Participant Discontinuation/Withdrawal from the Study ............................................................... 19 
7.3 
Lost to Follow-Up ............................................................................................................................... 20 
8 
STUDY ASSESSMENTS AND PROCEDURES ..................................................................................... 20 
8.1 
Efficacy Assessments .................................................................................................................................. 20 
8.2 
Safety and Other Assessments ....................................................................................................... 22 

  
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8.3 
Adverse Events and Serious Adverse Events ............................................................................... 23 
8.3.1 
Definition of Adverse Events (AE) ............................................................................... 23 
8.3.2 
Definition of Serious Adverse Events (SAE) .............................................................. 24 
8.3.3 
Classification of an Adverse Event .............................................................................. 24 
8.3.4 
Time Period and Frequency for Event Assessment and Follow-Up ....................... 26 
8.3.5 
Adverse Event Reporting .............................................................................................. 26 
8.3.6 
Serious Adverse Event Reporting ............................................................................... 27 
8.3.7 
Reporting Events to Participants ................................................................................. 27 
8.3.8 
Reporting of Pregnancy ................................................................................................ 27 
8.4 
Unanticipated Problems .................................................................................................................... 28 
8.4.1 
Definition of Unanticipated Problems (UP) ................................................................. 28 
8.4.2 
Unanticipated Problem Reporting ................................................................................ 28 
8.4.3 
Reporting Unanticipated Problems to Participants ................................................... 28 
9 
STATISTICAL CONSIDERATIONS .......................................................................................................... 29 
9.1 
Study Hypotheses.............................................................................................................................. 29 
9.2 
Sample Size Determination .............................................................................................................. 29 
9.3 
Populations for Analyses .................................................................................................................. 30 
9.4 
Statistical Analyses............................................................................................................................ 30 
9.4.1 
General Approach .......................................................................................................... 30 
9.4.2 
Analysis of the Primary Efficacy Endpoint(s) ............................................................. 31 
9.4.3 
Analysis of the Secondary Endpoint(s) ....................................................................... 31 
9.4.4 
Safety and Interim Analyses ......................................................................................... 31 
9.4.5 
Baseline Descriptive Statistics ..................................................................................... 31 
9.4.6 
Tabulation of Individual Participant Data .................................................................... 32 
9.4.7 
Exploratory Analyses ..................................................................................................... 32 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .............................. 32 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ........................................................... 32 
10.1.1 
Informed Consent Process ........................................................................................... 32 
10.1.2 
Study Discontinuation and Closure ............................................................................. 34 
10.1.3 
Confidentiality and Privacy ........................................................................................... 34 
10.1.4 
Future Use of Stored Specimens and Data ............................................................... 35 
10.1.5 
Key Roles and Study Governance .............................................................................. 35 
10.1.6 
Safety Oversight ............................................................................................................. 36 
10.1.7 
Clinical Monitoring .......................................................................................................... 36 
10.1.8 
Quality Assurance and Quality Control ....................................................................... 36 
10.1.9 
Data Handling and Record Keeping ............................................................................ 37 
10.1.10 
Protocol Deviations ........................................................................................................ 38 
10.1.11 
Publication and Data Sharing Policy ........................................................................... 38 
10.1.12 
Conflict of Interest Policy .............................................................................................. 38 
10.2 
Additional Considerations ................................................................................................................. 39 
10.3 
Abbreviations ...................................................................................................................................... 40 
10.4 
Protocol Amendment History ........................................................................................................... 41 
10.5 
Appendices ......................................................................................................................................... 46 
11 
TELEMEDICINE PROCEDURES AS DEEMED NECESSARY DUE TO COVID-19 ........................ 48 
12 
REFERENCES ............................................................................................................................................. 50 
13 
PROTOCOL SIGNATURE PAGE .............................................................................................................. 56 
 

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STATEMENT OF COMPLIANCE 
 
This study will be carried out in accordance with Good Clinical Practice (GCP) as required by the following: 
• 
United States (US) Code of Federal Regulations (CFR) applicable to clinical studies (45 CFR Part 46, 
and 21 CFR Part 56) 
• 
NIH Clinical Terms of Award 
All key personnel (all individuals responsible for the design and conduct of this study) have completed 
Human Subjects Protection Training. The protocol and informed consent form(s) will be submitted to the 
Institutional Review Board (IRB) for review and approval.  Approval of both the protocol and the consent 
form will be obtained before any participant is enrolled.  Any amendment to the protocol will first go 
through IRB review and approval by the IRB before the changes are implemented to the study.  In addition, 
all changes to the consent form will be IRB-approved; a determination will be made regarding whether a 
new consent needs to be obtained from participants who provided consent, using a previously approved 
consent form, if this becomes applicable. (i.e. if there is a requested change to the consent form during 
the course of this study) 
 
1 
 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
Controlling Hypertension through Education and Coaching in Kidney 
Disease (CHECK-D) 
Study Description: 
This project aims to deliver an evidence-based, patient-focused 
intervention that will improve blood pressure (BP) control and outcomes 
early in chronic kidney disease (CKD) care. It uses continuous quality 
improvement (CQI) methods to make education and coaching streamlined 
and efficient. We hypothesize that compared to patients in a control 
group, patients in the intervention group will have lower systolic blood 
pressure, and improved patient-reported measures. 
Objectives: 
 
Primary Objective: Identify the impact of a provider-led, coach-supported 
patient education intervention on patient blood pressure over one year 
using a cluster-randomized controlled trial.   
Secondary Objectives: 1) Optimize the process of delivering a provider-led, 
coach-supported patient education intervention prior to using it in a 
cluster-randomized controlled trial (under “Quality Improvement and 
Evaluation of the Integration of a CKD Encounter Decision Intervention 
(EDI) in a Primary Care Clinic”, HUM00152989); 2) Identify the impact of a 
provider-led, coach-supported patient education intervention on patient 
clinical and self-reported outcomes over one year using a cluster-
randomized controlled trial; and 3) Identify whether and to what extent 
implementation outcomes (provider adoption, fidelity, perceived 
usefulness) are associated with clinical and patient-reported outcomes.  
Endpoints: 
Primary Endpoint: Change in systolic BP between baseline and 12 months 
Secondary Endpoints: Change in diastolic BP between baseline and 12 
months; Slope of systolic and diastolic BP across all time points; serum 
creatinine; urine protein-creatinine ratio; estimated glomerular filtration 
rate (eGFR); patient medication adherence; chronic kidney disease (CKD) 

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knowledge; self-efficacy; motivation; satisfaction with care; self-reported 
blood pressure-related behaviors; perceptions of health coaching; provider 
adoption, fidelity, and perceived usefulness; visit time, total time patient 
spends in clinic visit at enrollment; change in Electronic Medical Records 
(EMR) BP between baseline and 12 months; change in study visit BP 
supplemented with EMR BP if missing; change in BP using all study visit 
and EMR BP values Not an ‘endpoint’ or outcome, but important to 
capture, will be patient characteristics.  
Study Population: 
Adults (21-85 years old) seen in participating clinics at the University of 
Michigan and Detroit Medical Center/ Wayne State University 
(DMC/WSU), who meet eligibility criteria (uncontrolled hypertension, CKD 
stages 3–5, full eligibility criteria in sections 5.1 and 5.2). Our target 
sample size is 450 patients. We expect an approximately equal distribution 
of men and women. Demographics are expected to reflect local 
community populations from which we recruit. These communities include 
clinics in Ann Arbor and outlying areas, and in and around Detroit, 
Michigan. Patients in the study have high blood pressure and kidney 
disease and thus are inherently more sick than the general population. 
Phase: 
N/A 
Description of 
Sites/Facilities Enrolling 
Participants: 
All 10 sites are located in the southeast Michigan area. The UM Family 
Medicine sites include Chelsea, Livonia, Dexter, Briarwood, Ypsilanti, and 
Domino’s Farms. The UM Internal Medicine sites include Northville and 
Brighton. DMC/WSU sites include the Canfield Med-Peds clinic and 
Internal Medicine clinic on Canfield. 
Description of Study 
Intervention: 
The entirety of the study intervention consists of a provider-led CKD 
worksheet called the Encounter Decision Intervention (EDI) and 4-6 health 
coaching calls.  
Study Duration: 
In total, 60 months, although additional analyses and manuscript writing 
may continue after the study has ended. 
Participant Duration: 
Twelve months. 
Related separate QI 
initiatives for this study 
A separate, unregulated QI sub-study (HUM00152989) covers the 
integration of the EDI into participating clinics. However, collection of 
study data from individual participants does not fall under the unregulated 
research category and will take place independently of the QI sub-study. 
Therefore, this study (HUM00136011) will cover collection of data for 
enrolled participants. This study will also cover health coaching for 
participants in intervention clinics. Patients who do not enroll in this study 
are not excluded from the related QI sub-studies. 
 
 
 
 
 
 
 
 
 
 

C H E C K- D Pr ot oc ol  
V ersi o n 2. 0 
H U M 0 0 1 3 6 0 1 1 
3 F e br u ary  2 0 2 6 
 
 
3 
 
 
 
1. 2  
S C H E M A  
L u ci d c h art 
 
 
 
 
 
 
 

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1.3 
SCHEDULE OF ACTIVITIES (SOA) 
 
Note: Times indicated in this table guide our study measures and time points. Our pilot work has shown 
that patient scheduling for activities requires flexibility to accommodate not only the study but the 
needs and schedules of patients. As such, times for data collection may show ‘windows +/- x days). Exact 
time points of data collection will be documented in study logs, and also accounted for during analyses.  
Procedures 
 
Before routine 
Primary Care Provider 
(PCP) appointment 
At routine PCP 
appointment 
Immediately after PCP 
appointment, but will 
allow up to + 7days 
Immediately after 
enrollment, but will 
allow up to 3 weeks** 
1 month after 
participant enrollment, 
+/- 7days** 
6 months after 
enrollment, +/- 7 
days** 
12 months after 
enrollment, +/- 14 
days** 
Screening and provider 
approval 
X 
 
 
 
 
 
 
Control-EDI or 
Intervention-EDI 
 
X 
 
 
 
 
 
Consent and 
Enrollment 
 
 
X 
 
 
 
 
Survey t0 
 
 
  
X* 
 
 
 
Survey t1 
 
 
 
 
X* 
 
 
Survey t2 
 
 
 
 
 
X* 
 
Survey t3 
 
 
 
 
 
 
X* 
Coaching baseline 
survey 
 
 
 
X 
 
 
 
Coach calls 
 
 
 
4-6 coach calls will take place between coaching 
baseline survey until 11 months after enrollment 
Blood pressure 
 
 
 
X 
X 
X 
X 
Biological Specimens 
(urine, blood) 
 
 
 
X 
 
 
X 
*Surveys may be completed online or on paper at home for subjects who cannot complete in clinic.  
** Please note that timeframes have been extended to allow for a larger tolerance window, now ranging from 3-6 months.  
 
2 
 
INTRODUCTION 
 
2.1 
STUDY RATIONALE  
Chronic kidney disease (CKD) is a serious and growing public health problem. A total of 20 million 
people, or 20% of U.S. adults ages 60 years and older, have CKD.1 The number of patients with end-stage 
renal failure is expected to reach over 750,000 by the year 2020.2,3 Patients with CKD are often not 
controlled to optimal blood pressure targets,  and experience 3.5 times higher rates of cardiovascular 
events, and 6 times higher rates of mortality compared to patients without CKD.4 Cardiovascular risk 
grows exponentially as disease advances4. 
 

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The scientific premise and rationale for this research is based on evidence that education and coaching 
improve outcomes in patients near dialysis and in patients with other chronic conditions, and will be 
successful in improving outcomes in pre-dialysis CKD as well. Education and coach support for patients 
near or at end-stage renal disease5-7 delays initiation of dialysis and increases survival.7 Patient 
education and health coaching improves outcomes in diabetes mellitus.8-10 Applying CKD-specific patient 
education and health coaching in primary care, with patients at earlier stages of kidney disease would 
likely improve BP control, reduce risk of cardiovascular events, and delay or abate renal failure. This 
project builds on pilot studies of a provider-delivered patient education intervention that improved 
patient-centered outcomes in pre-dialysis CKD,11 and is informed by studies identifying what patients 
and providers want and need from education interventions.12,13 It also takes advantage of CQI methods 
to make education and coaching streamlined and efficient, which is critical to intervention success and 
future dissemination. The six specific hypotheses to the aims are summarized in three overarching 
bullets below are further described in more detail in later sections: 
1. Compared to patients in a control group, patients receiving tailored education and health 
coaching will have lower blood pressure, more knowledge about CKD, higher self-efficacy, 
motivation and satisfaction with CKD care.  
2. Continuous quality improvement and systems engineering approaches will facilitate resources 
and process efficiency of this research and future dissemination. 
3. Providers will adopt with high fidelity the EDI and perceive it as beneficial and useful to care. 
 
2.2 
BACKGROUND  
The name and description of the study intervention:  The name of this study is CHECK-D (Controlling 
Hypertension through Education and Coaching in Kidney Disease). The objective of this research study is 
to test the impact of a provider-delivered patient EDI, followed with 12 months of health coaching 
focused on blood pressure control in patients who have moderate to severe CKD. A cluster-randomized 
controlled trial will compare outcomes in patients with CKD stages 3-5 between intervention and control 
groups in 10 primary care clinics (8 at the University of Michigan (UM), and 2 at Detroit Medical Center / 
Wayne State University Health System (DMC/WSU)). This study uses continuous quality improvement 
and systems methodologies to understand current clinic processes of care in order to optimize resource 
neutrality.  This methodology will support implementation and success of the study (HUM00152989) as 
well as allowing assessment of how an intervention like this can work in the ‘real world’ and not just for 
research.  
 
A summary of findings from nonclinical in vitro or in vivo studies that have clinical significance: 
Conclusive evidence shows that good blood pressure (BP) control reduces cardiovascular events and 
death in patients with moderate to advanced kidney disease (stages 3–5).14,15 A recent randomized 
controlled trial comparing the benefit of intensive versus standard BP control shows that intensive BP 
control lowers rates of fatal and nonfatal cardiovascular events and death (hazard ratio 0.75 in all 
patients; 0.82 in subgroup with CKD).15 It also reduces risk of all-cause mortality.15 When BP is well 
controlled, patients experience lower risk of CKD progression as well.16-18 15 19 20,21 
Current mechanisms of care do not ensure patients who have CKD are educated and supported to 
achieve optimal blood pressure (BP) management. High BP is common, severe, and not well controlled 
in patients with CKD.17,22,23 As few as 40% of CKD patients achieve recommend BP targets.1,22 There are 
many barriers to achieving good BP control. At least two are patient-centric. First, many patients who 
have CKD do not understand their diagnosis, its implications or how important achieving good BP is for 
reducing their risk of cardiovascular events and CKD progression.24,25 Currently, patients who have CKD 
fare no better adhering to medications or lifestyle changes, despite their high risk for complications, 

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compared to patients without CKD.26 Second, promoting patient behaviors to improve outcomes, 
including BP control, requires coordinated programs of education and support over time. The best 
model of education and support for patients with CKD is yet to be determined.27,28  
 
A summary from relevant clinical trials: Patient-focused education and health coaching may improve BP 
control and outcomes in patients with CKD. This is based on success from prior studies in other chronic 
conditions. Patient motivation and healthy behavior change require patients to have knowledge of their 
chronic condition and the self-efficacy to do what is needed to stay healthy.29 National models of 
chronic care promote educating and supporting patients early in the care continuum.30 Patient 
education and coaching reduces hemoglobin A1C% in patients with diabetes mellitus,31,32 lowers re-
hospitalization rates in patients with pulmonary disease,33 reduces complications in spinal cord injury,34 
and improves care experiences in low-income patients with multiple chronic conditions.35  
While not all interventions have been successful,36-38 multiple projects targeting patient education and 
support have met goals of improving clinical outcomes,8-10,39 reducing disease-related complications,33,34 
and improving the patient care experience.32,35 Coaching varies, but is generally accepted to be “the 
practice of health education…and promotion…to enhance the well-being of individuals and to facilitate 
the achievement of health related goals.”40 A successful coaching program, and the model for this 
proposal, is Sepucha, Belkora et al.’s “Consultation Planning Program.”41-44 In addition, this study 
benefits from a robust study team that includes experts with years of research and practical experience 
in health behavior, shared medical decision making, and health coaching. Patients using education and 
coaching programs such as these, experience higher quality care, make better care decisions, and have 
greater satisfaction.41-44 Providers report higher satisfaction with patient-provider visits as well.41  
 
Discussion of important literature and pilot data that are relevant to the trial  (reference citations are 
listed in Section 17): Relevant literature to this study is highlighted above. However, in addition to 
literature, the PI and investigative team have put a significant amount of work into developing pilot 
data that supports this research. Below describes this pilot work. Dr. Wright Nunes led the design, 
administration, and validation of a comprehensive survey that quantitatively measured disease 
knowledge in 556 patients with CKD.25 Results showed most patients do not understand their CKD 
diagnosis, its implications, treatments, or what they must do to optimize kidney health—even when 
under care of nephrologists.25 Thirty-percent of patients under care of a kidney doctor do not even 
realize that they have chronic kidney disease. The survey identified an important link between BP 
control and knowledge. Patients who know their BP goals achieve better BP control compared to those 
who do not.13 But patients do not understand how dietary behaviors impact their BP or how to 
implement dietary sodium restrictions.45 Additional unpublished analyses revealed that patients 
perceive physician-providers as their most valuable and trusted resource for CKD information. Work in 
other diseases supports this.46,47  
This preliminary data informed an educational intervention (referred to from now on as an 
encounter decision intervention, or “EDI”) that was pilot tested in 155 patients.11 The EDI was adapted 
from the National Kidney Disease Education Program patient education worksheet. 48 It is a one-page 
paper document designed for providers to use during visits when talking to patients about CKD and 
management goals.48 The EDI was tested in nine nephrology clinics. Patients who received the EDI had 
more knowledge about their CKD diagnosis compared to a usual care cohort, and 98% recommended it 
for future use. It took minutes to review, and providers liked it.11 
To develop this for use in primary care, Dr. Wright Nunes led a series of structured interviews in 
50 patients and 25 physician-providers at the University of Michigan. Patients said they wanted CKD 
information earlier in care. Patients feel CKD diagnosis information from providers is lacking and too 
general. Patients feel that current mechanisms of care do not provide them with the support they need 

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to effect behavior change to avoid CKD complications and disease progression.12 Both primary care49 and 
nephrology providers50 say discussing a CKD diagnosis with patients is challenging and that education for 
patients early about CKD is important. But evidence-based patient education tools are lacking.50 
Additional surveys in 202 patients enabled the study team to quantitatively summarize patient priorities 
for education topics, select the best format for education materials, and identify resources patients felt 
were most important. Patients also prioritized their barriers to optimal CKD self-management. The 
number one barrier patients cited was not having motivation to do what is needed to improve health, in 
particular when it came to being active and eating healthy. 51,52  
Informed by the work above, Drs. Wright Nunes and Co-I’s launched a pilot study to optimize 
CKD education and support in primary care. Using a collaborative multidisciplinary team (including 1 CKD 
patient, 2 primary care physicians, 1 medical assistant, 1 check-out staff, 2 clinic admin leads, 1 
information technology representative) they adapted the paper EDI into an electronic format for the 
EMR, and created a process map for using it in clinic, by the PCP, during routine follow up visits for 
patients.  
Lastly, investigators in this study have developed and tested a formalized coaching protocols 
based on years of leading research developing patient decision aids for patient shared decision making, 
communication tools, and coach support interventions.53-58 Investigators on this team (Drs. Fagerlin, 
Resnicow) and tested coaching protocols in a precursor conditions of CKD—diabetes mellitus and 
obesity. From this work we’ve learned that most patients (82%) felt it helpful to talk with the coach 
about their questions, and 85% found it helpful to talk about their values in care (remaining were 
neutral). Physicians also like the coaching—80% thought coaching helped patients ask better questions 
and helped patients better understand their treatments.  
 
Applicable clinical, epidemiological, or public health background or context of the study: As stated in 
section 2.1, chronic kidney disease (CKD) is a serious and growing public health problem..1 The number 
of patients with end-stage renal failure is expected to reach over 750,000 by the year 2020.2,3 The risks 
of progression to renal failure, cardiovascular events, and death are significantly higher in patients with 
CKD compared to those without CKD.4 High blood pressure accounts for one of the top two leading 
causes of progression of CKD to renal failure, yet over 40% of patients with CKD are uncontrolled. This 
research will deliver a tested educational and coaching intervention with an efficient process of delivery, 
to reduce blood pressure in patients who are not controlled to ultimately improve outcomes.   
 
Importance of this study and relevant issues / controversies: Reviews show that rigorous evidence-
based patient education and support programs are lacking early in CKD care.59-61 There are several 
additional limitations of existing research: 1. Prior research has often focused only on  one-way delivery 
of patient education, 2.  Health coaching is not well studied in CKD, and 3. Prior studies have often given 
education interventions to patients too late in the process of disease—often when they have already 
approached total renal failure (end-stage renal disease, ESRD) 5-7 In addition, most education-related 
studies in CKD are of short duration (6 months or less) and are not focused on clinical outcomes.59 There 
is little examination of how implementation or system factors mediate intervention success or whether 
interventions can be sustained in the real world.60,62  
 
This research will address many of these issues / controversies: 1. This proposal will deliver an 
intervention to address gaps in education and coaching early in the CKD care continuum. 2. This 
research includes an examination of impact on clinical outcomes over a long duration. 3. This research 
uses continuous quality improvement (CQI) and a systems-driven approach to make patient education 
and coaching unified and efficient (HUM00152989). Further, it will examine whether provider and 
system factors mediate intervention impact. 4.  This research benefits from a pilot-tested patient EDI 

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that was informed by patients and primary care providers, and serves as launch for coaching support 
calls that will follow.  
 
2.3 
RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
Participants face certain potential risks. This study is no more than minimal risk. The potential risks to 
participants include 1) breach of confidentiality of medical records, surveys, or conversations which 
could result in psychological distress, 2) Risk of psychological distress from coaching or surveys related 
to answering questions, 3) potential distress caused to patients who may have a better understanding 
about their diagnosis, disease management, and self-care after receiving our intervention, 4) the time it 
takes to fill out surveys, or for patients enrolled who will get the coach calls—the time to participate in 
coach calls, and 5)  A small risk of bruising and a rare chance of local infection associated with standard 
venipuncture to collect blood samples at two time points in the study.  
 
Risks related to surveys and coaching or provider conversations will be minimized in that these 
conversations will only be done in an environment that supports individual discussion and 
confidentiality of responses. Any patient experiencing any untoward reaction will have the option to 
discontinue their participation in the study. Removal of participants from further participation in the 
study will be mandatory for serious or potentially serious side effects. There is a potential risk of loss of 
confidentiality and patient privacy. We are mindful of the sensitive nature of patient’s medical records 
and have the utmost concern for the human subjects who will be part of this study and will take steps to 
ensure protection of confidentiality (outlined in section 10.1.3).  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
Overall, the risks are relatively small, and the potential information gained will add critical knowledge 
necessary to optimize care and improve cardiovascular and renal disease related outcomes in a 
population of patients at high risk for morbidity and mortality (with CKD and HTN). Information gained 
from this research will form more evidence-based medical literature in early CKD. It will provide critical 
evidence for future steps in planning and potential dissemination. Patients will obtain direct benefits by 
receiving education and coaching aimed to modify their risks and improve their health outcomes.  
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
The potential benefits at both the national level (knowledge to be gained and potential future 
dissemination) and at the individual-level outweigh the potential risks. This study is no more than 
minimal risk; Therefore, the risks are reasonable in relation to the anticipated benefits. 
 
3 
OBJECTIVES AND ENDPOINTS  
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
Identify the impact of a provider-
led, coach-supported patient EDI 
on patient blood pressure over one 
Change in systolic blood pressure 
between baseline and 12 months 
 
 
Blood pressure control 
is a primary 
educational focus of 
the EDI.  Systolic BP 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
year using a cluster-randomized 
controlled trial. 
was chosen because it 
most consistently 
relates to 
cardiovascular and 
other end outcomes in 
kidney disease.63,64 
Secondary 
 
 
Optimize the process of delivering 
a provider-led, coach-supported 
patient EDI prior to using it in a 
cluster-randomized controlled trial. 
(These QI activities are covered in 
approved QI IRB HUM00152989 
and will be support seamless 
implementation into current 
patient flow at the clinics) 
Visit time (length of time provider 
spends with patient), total time in 
clinic (length of time between patient 
check-in and check-out) 
We will create the 
most efficient process 
for integrating and 
applying the patient 
EDI and coaching so as 
not to disrupt clinic 
flow and patient follow 
up.   
Identify the impact of a provider-
led, coach-supported patient EDI 
on patient clinical and self-reported 
outcomes over one year using a 
cluster-randomized controlled trial. 
Slope of systolic BP between all 
timepoints, change and slope of 
diastolic BP between all timepoints, 
serum creatinine, urine protein:urine 
creatinine, Egfr, medication 
adherence, CKD knowledge, self-
efficacy, motivation, patient 
satisfaction with CKD care, self-
reported blood pressure-related 
behaviors, perceptions of health 
coaching, change in EMR BP between 
baseline and 12 months, change in 
study visit BP supplemented with 
EMR BP if missing, change in BP using 
all study visit and EMR BP 
We are interested in 
knowing the impact of 
the EDI and health 
coaching on other 
clinical and patient-
reported outcomes 
related to kidney 
disease – as well as in 
knowing whether 
patients like the 
intervention. 
Identify whether and to what 
extent implementation outcomes 
(provider adoption, fidelity, 
perceived usefulness) are 
associated with clinical and patient-
reported outcomes. 
Provider adoption, fidelity, and 
perceived usefulness  
An unresolved issue in 
the field of patient 
education and support 
is how to evaluate and 
conceptualize 
successful 
implementation of 
education and support 
programs.65 This 
research proposal is 
not an implementation 
science study, 
however, will evaluate 
the intervention 

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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
implementation by 
asking provider 
perceptions of the 
intervention usefulness 
and whether providers 
adopt its use. 
Tertiary/Exploratory  
 
 
Cost effectiveness of coaching 
Hours worked x wages of coaches at 
study end—this is NOT a formal cost 
analysis. 
For dissemination, 
replicability planning. 
 
A list of all study measures is included in the appendices, section 10.5. 
 
4 
STUDY DESIGN  
 
4.1 
OVERALL DESIGN 
This study examines the impact of an education and coaching intervention in primary care for patients 
who have CKD and high blood pressure. It is a multi-site cluster-randomized controlled trial, where the 
units of randomization are 10 clinics.  Patients who meet eligibility criteria in intervention clinics and 
who enroll in the study will receive:  An Encounter Decision Intervention (EDI) reviewed by their primary 
care doctor that gives the patient information about their CKD diagnosis and BP goals. Then, the patient 
will receive health coaching to improve blood pressure via 4-6 coach calls over the next 11 months. 
Patients who meet eligibility criteria in control clinics and who enroll will receive: A Control-EDI that 
provides only generalized information about CKD and where patients can go to get more information. 
Outcome measures are systolic and diastolic BP, clinical laboratory measurements (blood, urine), 
patient, provider, and clinic characteristics, and surveys administered to patients and providers.   
   
This protocol outlines in detail the patient enrollment for implementing the EDI, collecting study 
measures, and health coaching. One related but separate study covers activities on optimizing 
implementation of study activities using continuous quality improvement (CQI) methods: 
 
Quality Improvement and Evaluation of the Integration of a CKD Education Tool in a Primary 
Care Clinic – HUM00152989: This IRB applies to optimizing implementation of intervention 
activities to ensure they will be most efficient and seamless so as not to disrupt current clinical 
practices nor patient flow at the participating clinics.  
 
In this multi-site cluster-randomized controlled trial, clinics are the unit of randomization and will be 
randomized to either the intervention or control groups.  Clinics will be stratified by primary care 
provider discipline, geographic location and socio-economic status to ensure treatment balance on 
those factors.  
 
Aim 1: Optimize the process of delivering a provider-led, coach-supported patient education 
intervention prior to using it in a cluster-randomized controlled trial.  
Hypothesis 1: CQI and systems approaches will facilitate resource and process efficiency comparing 
intervention and control groups. 

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Aim 2: Identify the impact of a provider-led, coach-supported patient education intervention on 
patient clinical and self-reported outcomes over one year using a cluster-randomized controlled trial.  
Hypothesis 2: Compared to patients in the control group, patients in the intervention group will have 
lower blood pressure. 
Hypothesis 3: Compared to patients in the control group, patients in the intervention group will 
experience higher Egfr, greater reductions in urine protein, and higher medication adherence. 
Hypothesis 4: Compared to patients in the control group, patients in the intervention group will have 
greater knowledge about CKD, and higher self-efficacy, motivation, and satisfaction with CKD care. 
 
Aim 3: Identify whether and to what extent implementation outcomes (provider adoption, fidelity, 
perceived usefulness) are associated with clinical and patient-reported outcomes. 
Hypothesis 5: Within intervention clinics, provider adoption, perceived usefulness of, and fidelity to the 
provider-delivered EDI will be high and positively associated with clinical and patient-reported 
outcomes. 
Hypothesis 6: Providers will perceive the intervention as beneficial and feasible for future translation 
into community settings. 
 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
This design minimizes the potential problem of contamination.66 It would be difficult for trained 
providers who are accustomed to using the EDI and whose patients have access to regular health 
coaching over a year not to change practice patterns depending on the patient to whom they are 
providing care. It is also an appropriate design for optimizing pragmatic trials such as this.66   
 
4.3 
JUSTIFICATION FOR DOSE 
 
Not applicable 
 
4.4 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if he or she has completed all phases of the 
study including from enrollment through the last study measures, 12 months after enrollment (see 
Schedule of Activities (SoA), Section 1.3).  
 
For participants who request more information about the survey, we may refer them to resources 
where the survey have been validated and published at the end of their participation as appropriate. 
 
Study enrollment will be complete after meeting the study’s pre-specified number of target participants 
through 12 months of enrollment and completion of their final study measures. Thereafter, analyses, 
reporting and evaluative steps will occur through completion of the 60-month research project timeline.  
5 
STUDY POPULATION 
 
5.1 
INCLUSION CRITERIA 
All patients coming in for appointments at participating clinics will be screened for eligibility, and 
healthcare providers will be prompted to review the EDI with eligible patients. A waiver of consent is 

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requested for the EDI to ensure the safety of patients and that the intervention is reaching an unbiased 
population of CKD patients. Patients will provide informed consent after the EDI, but prior to completing 
study measures and health coaching. 
 
Inclusion criteria will include: 
 
1. Aged ≥21 and ≤ 85 years 
2. Has diagnosis of CKD stage 3, 4, or 5 documented in medical record (which is equivalent to an 
estimated glomerular filtration rate, Egfr < 60 ml/min/1.73 m2). 
3. Aware of CKD diagnosis* (assessed by screening questions) 
4. Has diagnosis of hypertension documented in medical record AND most recent BP within the 
last year meets criteria of uncontrolled hypertension (>130 mmHg, and/or a diastolic blood 
pressure >80 mmHg noted in an ambulatory care setting within the past one year15,67) 
5. Estimated glomerular filtration rate (Egfr) of <60 within the last 18 months documented in the 
medical record. 
 
*Note: This is only assessed after the patient completes the visit. The patient does not need to be aware 
of CKD diagnosis prior to receiving the EDI; they only need to be aware prior to consenting to complete 
the study measures and/or receive health coaching. Whether or not the patient actually received the 
EDI in clinic does not affect their eligibility for the health coaching and study measures. 
 
In addition, patients must be able to provide informed consent (see below for exclusion criteria). Prior to 
collecting study measures and health coaching, we will obtain either a signed and dated informed 
consent form or a verbal consent when using phone consent.  Inherent in informed consent is a stated 
willingness to comply with all study procedures and availability for the duration of the study.  
 
5.2 
EXCLUSION CRITERIA 
 Exclusion criteria are: 
 
1. Currently on dialysis permanently (i.e. are considered “end-stage renal disease” and receiving 
dialysis) 
2. Previous kidney transplant 
3. Pregnant (indicated by medical record or if patient self-identifies as pregnant) 
4. Has cognitive, language, or vision impairment(s) or language barrier that would prohibit 
participating in education, taking surveys, or participating in coaching activities  
5. Has terminal illness. 
 
It is not our intent to recruit terminally ill patients. If there are flags in the chart or a patient’s provider 
raises the issue, we will not approach for recruitment. 
 
5.3 
LIFESTYLE CONSIDERATIONS 
Not applicable. 
 
5.4 
SCREEN FAILURES 
For the purposes of this study, we will define screen failures as patients who complete the screening 
questions to determine if they are aware of their CKD diagnosis (“Has your doctor ever told you that you 

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have, or do you have, any of the following: kidney disease, renal insufficiency, chronic kidney disease, 
low kidney function, or a kidney problem?”) but deny having any of these conditions, and are not 
subsequently entered in the study.  If a patient is found to be unaware of their CKD diagnosis, a member 
of the study team will inform the patient’s primary care provider, who will determine the appropriate 
next steps for discussing CKD with the patient (as in usual care).  The role of research personnel is not to 
inform the patient of their diagnosis; this will remain the responsibility of the healthcare provider caring 
for the patient. 
 
A minimal set of screen failure information is required to ensure transparent reporting of screen failure 
participants, to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing 
requirements and to respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, and any serious adverse event (SAE). 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) because they are 
not aware of their diagnosis of CKD may be rescreened at a future date for study enrollment.  
 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
There are ten outpatient clinics participating in this research study.  Of these, eight are affiliated with 
the University of Michigan, located in Ann Arbor and surrounding areas.  Two clinics are affiliated with 
Wayne State University/Detroit Medical Center, located in Detroit.  All clinic directors have agreed to 
have their clinics participate in this study.  Using site representatives to provide input on how we 
implement study activities seamlessly into clinics will also foster local champions for project 
participation. It is possible that a clinic will drop out of the study. We feel this is very unlikely given 
strong support from clinics and leadership. However, if this occurs prior to enrollment, we will try to 
identify other clinics to participate, a strength being that clinics in this study are affiliated with large 
health systems that have many other potential clinics. 
 
Based on administrative data and queries, the annual number of unique adult patients meeting 
eligibility criteria at each clinic is on average 40-60 yearly.  These are conservative numbers because 
estimates are drawn from queries of patients with an Egfr <45 ml/min/1.73 m2.  Our eligibility criteria 
(CKD stages 3-5, Egfr <60 ml/min/1.73m2) will likely yield a larger number eligible.  The clinics were 
selected because they 1) all met eligibility criteria, 2) have reasonably large case volume for patient 
enrollment, 3) offer a mix of academic-community and academic-urban practices, 4) include diverse 
geographical and socio-demographic variability that will increase the generalizability of the data, and 5) 
share previous successful collaborations with investigators. 
 
The target sample size for this study is 450 participants, but we may enroll more to ensure we have 
sufficient data for analysis.  Eligible participants will be recruited without regard to gender, race, or 
ethnicity.  Although for this study we will not aim to meet a specific quota for any particular age group, 
gender, race, or ethnicity, typical gender and race/ethnic distributions for ambulatory clinics at both 
institutions are combined for total enrollment and include approximately 24% African American 
patients, 50% female, 7% Hispanic or Latino, 12% other or combined races (American Indian/Alaska 
Native, Asian, Native Hawaiian or Other Pacific Islander, more than one race) of the ages 21 to 90 years 
old.  Demographics are expected to reflect local community populations around clinics participating, 
including Ann Arbor and outlying areas and Detroit and its outlying areas.  By nature of kidney disease 
many eligible patients may be older; however, any adult meeting eligibility criteria may participate.  
Patients in the study will have high blood pressure and kidney disease and thus are inherently more sick 

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than the general population. They are at higher risk of cardiovascular events, death, and morbidity 
compared to other patients with other chronic conditions and compared to the general population.  
 
Eligible participants will be identified by screening the clinics of participating primary care providers.  
Participants may be screened for eligibility and consented either by phone or in person at their 
appointment with the primary care provider in a participating clinic.  As required, this study will be 
posted on ClinicalTrials.gov, where interested, eligible participants may contact the study team to enroll. 
 
Lastly, we will also use patient incentives as they’ve shown beneficial to patient participation in ongoing 
studies. Remuneration will occur at enrollment and with additional incentives along the study duration. 
 
5.6 
ADDITIONAL SUBGROUP (AIM 3) 
In Aim 3 of this study, we will evaluate the adoption, fidelity, and perceived usefulness of the 
intervention among primary care providers. This will include primary care providers who have permitted 
the study team to screen their patients for eligibility and have been asked to discuss the EDI with their 
patients. We will distribute a provider survey to these providers via email, mail, or in person at the 
clinics. 
 
6 
STUDY INTERVENTION 
 
6.1 
STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
We will use a cluster-randomized controlled trial design to assess the impact of patient education and 
coaching on outcomes. Ten clinics are the unit of randomization and will be randomized to either the 
intervention (5 clinics) or control groups (5 clinics). This design minimizes the potential problem of 
contamination between patients or providers within one clinic.66 
 
Patients within clinics assigned to the control group will be given a Control-EDI about kidney disease in 
general (not tailored to the patient) during their enrollment visit. A waiver of consent is requested for 
the EDI, and an informed consent for the data and biospecimen collection will be obtained after their 
visit. This information sheet will be given to the patient by a primary care provider during their 
enrollment visit. After the enrollment visit, if they consent, patients in the control group will answer 
survey questions, have blood pressure taken and be asked to provide one blood test (to check Egfr and 
serum creatinine) and one urine test (to check urine protein:creatinine—which is one urine test that 
combines analysis of protein and creatinine into one test). The patient will receive follow up calls from 
study personnel at approximately 1, 6, and 12 months after their enrollment visit. The purpose of these 
calls is to remind patients to meet with the study team for their study visits at 1, 6, and 12 months after 
initial enrollment, where the patient will answer survey questions, have blood pressure taken, and at 
the last visit (12 months after enrollment) provide one blood (Egfr and serum creatinine) and urine test 
(urine protein:creatinine). 
 
Patients within clinics assigned to the intervention group will be given a personalized Intervention-EDI 
during their enrollment visit. A waiver of consent is requested for the EDI, and an informed consent for 
the data and biospecimen collection and health coaching will be obtained after their visit. The 
Intervention-EDI will be tailored with personalized information specific to the patient (the patient’s most 

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recent blood pressure, their urine protein level and most recent Egfr-estimated glomerular filtration 
rate). There is also a space for their provider to type in a sentence about any goals or take away points 
they want the patient to remember. After the enrollment visit, patients will answer survey questions, 
have blood pressure taken and be asked to provide one blood test (to check Egfr and serum creatinine) 
and one urine test (to check urine protein:creatinine). The patient will receive follow up calls from study 
personnel at approximately 1, 6, and 12 months after their enrollment visit. The purpose of the calls is 
to remind patients to meet with the study team for their study visits at 1, 6, and 12 months after initial 
enrollment, where the patient will answer survey questions, have blood pressure taken, and at the last 
visit (~12 months after enrollment) provide one blood (Egfr and serum creatinine) and urine test (urine 
protein:creatinine). 
Patients in the intervention group will also receive health coaching through calls from a health 
coach after their enrollment. The goal for the number of coach calls will vary based on individual patient 
needs, however, we are targeting approximately 4-6 calls in number, over the 12-month period of the 
study. There are 4 topics areas related to blood pressure and CKD coaching that will be the focus of the 
calls, so the target number of coach calls is expected to take approximately four to align with one call 
per topic area. However, the actual number of coach calls will include first, getting a baseline 
assessment on where the patient feels they are at related to each health behavior which may take for 
some patients a full 30 minutes. Further, additional calls to the patient may be more or less depending 
on individual patient needs. It is important to the patient-centered autonomy and values/goals setting 
upon which coaching is grounded to be flexible to the patient. Coaches work with the patients to 
determine the areas patients feel they need for support in health behavior changes related to blood 
pressure control and CKD. Further, coaches provide motivational interviewing with the patient to 
support implementation of those changes. Lastly, coaches will have pre-determined and vetted 
educational resources that are pulled from and adapted from the UM patient education online 
resources (careguides.umich.edu/kidney).  These are sent to patients who may need or request specific 
information on behavior topics related to blood pressure and kidney disease.  
6.1.2 DOSING AND ADMINISTRATION 
Not applicable 
 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY   
 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
Not applicable 
 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND LABELING 
Not applicable 
 
6.2.3 PRODUCT STORAGE AND STABILITY 
Not applicable 
 
 
6.2.4 PREPARATION 
Not applicable 
 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 

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The nature of this education and coaching study does not allow for blinding of patients or their 
providers to education or coaching, or to getting study measures at time points along the study. 
Therefore, providers and patients might be prompted to engage more in care than they might 
otherwise. However, if this occurred, it would occur in both patients from control and intervention 
clinics, and thus likely work against our hypothesis uniformly–so it is unlikely we would have Type I 
error. It is also possible that patients who agree to participate in this study will be significantly different 
than those who decline. However, we believe patients should choose the level of involvement they have 
in their care. We do not endorse mandatory autonomy70 and believe that patients who are 
uncomfortable taking a fuller role in their own care should not be forced to. 
 
This cluster randomized trial design (each clinic is a cluster) was chosen because it minimizes the 
potential problem of contamination.66  Clinics are randomized and assigned to either intervention or 
control. Thus, patients and providers within each cluster will only be exposed to either the intervention 
or control. It is also an appropriate design for trials that include pragmatic aspects such as this.66   
 
6.4 
STUDY INTERVENTION COMPLIANCE 
All proposed research activities will be approved by the Institutional Review Boards at UM (the 
University of Michigan) and DMC/WSU (Detroit Medical Center / Wayne State University (WSU) Health 
Systems). A Data Safety and Monitoring Plan will be put into place as part of the study’s manual of 
operations–to monitor patient safety and evaluate the ability of the investigators to conduct the 
proposed study with utmost regard for patient / provider protection and confidentiality, and is further 
described in section 10, and will be included in the MOP.  
 
At study start, all research personnel, coaches and staff will undergo training and in-service meetings 
about the study, their role in the study, all applicable procedures relevant to their job duties, and the 
importance of data security and compliance. Further, all study personnel are required to complete and 
be certified by the Program for Education and Evaluation in Responsible Research and Scholarship 
(PEERRS) or equivalent, and maintain this certification.  
 
Standard reporting forms to track study activities (research screening, recruitment, enrollment and 
obtaining study measures) will be created and included in the MOP. All research personnel will be 
trained in the forms, how to use them, with review of confidentiality, secure storage and documentation 
protocols. A review of these reporting forms will occur no less frequently than quarterly for all 
participating sites (UM and DMC/WSU). Any diversions from expected protocols will be reviewed by 
study team members and PI, with root cause analyses to identify contributors, and resolution.   
 
Providers within clinics assigned to the control group will receive a standardized CKD education session, 
to review the project, reinforce meaning and management principles of CKD, BP targets, and BP 
management aligned with current guidelines. During this session providers will receive brief didactics to 
reinforce communication principles at the patient-provider interface,71 and examples of how to review 
the control-EDI with patients during clinic visits.  
 
Providers in intervention clinics will also receive standardized CKD education sessions,71  with additional 
training for intervention providers on using the Intervention-EDI. Education sessions are based on prior 
training that the PI developed and led which on average took ~45 minutes to complete.11 The slide set 
for the providers along with instructive materials will be included in the MOP.  

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Providers are often busy, and every provider may not be able attend in person sessions. Thus, a web-
based, concise overview of the provider training for providers in both control and intervention clinics 
will be made available for providers to refer back to, that will include a short online video explaining the 
study purpose and a step by step tutorial on expectations for the study.  The materials adapted for this 
online resource, along with its URL will be included in the MOP.  
 
Coach recruitment: Health coaches will have a Master’s Degree in health education and health behavior, 
counseling psychology, or social work, or training in health behavior with degrees in nutrition (i.e. 
registered dieticians). Coaches will be evaluated and hired that demonstrate empathetic and 
interpersonal skills as determined by their responses to appropriately crafted scenarios.  
 
Coach training: Coaches will receive a 2-3 day training program led by the PI and study team members 
with expertise in health coaching, and advised by Dr’s Resnicow and Fagerlin. 
 
A core element is that this training is interactive and in-person to enhance coach confidence, skills, and 
effectiveness for this study. This training session offers approximately 8-10 hours of face-to-face training 
in Motivational Interviewing (MI), 1 hour of face-to-face training in behavioral therapy, and additional 
training for CKD, high blood pressure and the study protocol. Training sessions will be led by Dr. 
Resnicow with input from Dr. Fagerlin and with assistance from study team members with expertise in 
health coaching. 
  
For two decades, Dr. Fagerlin has developed through research pragmatic approaches to shared decision 
making and patient engagement in chronic disease. For over 25 years, Dr. Resnicow has developed and 
refined a curriculum that includes a mix of didactic and experiential activities, teaching MI skills with real 
time constructive feedback. Core MI techniques include the use of reflective listening, allowing the 
client to interpret information, agenda setting, rolling with resistance, building discrepancy and eliciting 
self-motivational statements or “change talk.” Training will include standardized, role-played patient 
encounter that is videotaped during the training session, with scoring using the One Pass system.  
 
One Pass is a MI fidelity assessment and supervision tool; it requires raters to listen to a clinical 
encounter only once before providing feedback. While preliminary feedback will be given immediately 
to the coach, they will also receive a consultative phone call from an MI trainer at the University of 
Michigan several weeks later, during which they will discuss their performance in greater detail. To 
enhance skill acquisition and reduce skill atrophy, we will provide each participant with training 
materials to enhance their core skills of reflective listening, building motivation, and eliciting change 
talk. The training materials will demonstrate a range of full clinical scenarios relevant to the project 
using simulated examples.  
Remaining time in the training session will be used to review the study protocol.  
 
Coach call logging, tracking, monitoring: A novel aspect of ensuring compliance and documentation of 
coach calls for enrolled patients in the intervention clinics, is in the fact that this study will be using and 
online study dashboard, referred to as the health coaching portal.  The study team at UM has created 
this in concert with the Center for Health Communications Research, and it is based on prior work 
(copied from and adapted) using a similar online portal by co-investigator, Dr. Ken Resnicow for a study 
of 3000 patients to use coaching to reduce childhood obesity. The portal provides a graphical user 
interface, for coaches that include coach surveys and scripts to use during coach calls for each 
participant. Its primary function is to allow coaches to schedule, track, deliver and document their coach 
calls with enrolled patients during the intervention, within one centralized location –i.e. the portal. It 

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supports standardization, and excellent means for tracking and monitoring coaching for participants. It 
also provides study personnel, password protected access to study related coach activities as described 
below: 
 
 
Content 
Use 
Access 
Storage 
 
Participant contact 
information 
Research intervention 
delivery only. 
Coach, study team 
members, patient 
participant 
UM secure server 
Baseline coach 
surveys/scripts 
Research and 
intervention. 
Coach, study team 
members, patient 
participant 
UM secure server 
Follow up coach 
surveys/scripts 
Research and 
intervention. 
Coach, study team 
members, patient 
participant 
UM secure server 
>Coach counseling 
notes 
>Summary notes that 
can be sent to primary 
care provider 
>Summary notes for 
participants 
Research and 
intervention delivery 
and clinical. 
Above, plus providers 
of patients enrolled in 
intervention 
UM secure server 
>Education resources 
for patients 
>Education and 
support resources for 
coaches 
Research and 
intervention delivery 
and clinical. 
Study procedures 
reference. 
Coach, study team 
members, patient 
participant 
UM secure server 
 
 
Once participant enrollment begins, all calls will be recorded to facilitate the provision of ongoing 
feedback by an MI (motivational interviewing) supervisor to coaches about their MI skills, and to review 
and resolve any concerns related to adherence and compliance with coaching surveys and scripts. MI 
supervisors are also clinicians and researchers who are on the study team—with expertise in MI.  
 
6.5 
CONCOMITANT THERAPY 
Not applicable. 
 
6.5.1 RESCUE MEDICINE 
Not applicable. 
 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
 
7.1 
DISCONTINUATION OF STUDY INTERVENTION 
 

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Discontinuation from coaching does not necessarily mean discontinuation from the study, and 
remaining study procedures will be completed as indicated by the study protocol.  If a clinically 
significant finding is identified (including, but not limited to changes from baseline) after enrollment, the 
investigator or qualified designee will determine if any change in participant management is needed. 
Any new clinically relevant finding will be reported as an adverse event (AE). 
 
The data to be collected at the time of study intervention discontinuation will include the following: 
• 
Reason for discontinuation 
• 
Whether discontinuation was patient-driven (patient non adherence or chose to discontinue), 
study-related (investigator-driven per discontinuation protocols), or other 
• 
The time from enrollment to discontinuation. 
For any patients lost to follow up, we will use any data collected from participants lost to follow up from 
enrollment to the point at which they were lost to follow up 
 
7.2 
PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE STUDY 
Clinic ‘participants’ (i.e. the specific clinics that each are a cluster) may drop out of the study. We feel 
this is very unlikely given strong support from clinics and leadership at each clinic. However, if this 
occurs prior to enrollment, we will try to identify other clinics to participate, a strength being that clinics 
in this study are affiliated with large health systems that have many other potential clinics.  
 
Patient-Participants are free to withdraw from participation in the study at any time upon request. They 
can withdraw by informing their coach (if receiving the intervention), a study team member, or directly 
to Dr. Julie Wright, the study Principal Investigator. If a patient withdraws from the intervention clinics, 
his/her study-related coach calls will end, he/she will no longer receive surveys / coach calls, he/she will 
no longer have access to the health coaching portal, and all contact information will be deleted. If a 
patient withdraws from the control or intervention clinics, they will no longer be contacted to be 
reminded to come in for study measures/visits or to take surveys or when applicable, provide biological 
samples (enrollment and last visit). We will continue to securely store and analyze all data that the 
parent has provided up to the date of withdrawal. 
 
An Investigator may discontinue or withdraw a participant from the study for the following reasons: 
 
• 
Newly patient self-identified pregnancy during course of the study (this is exclusion criteria) 
• 
Significant study intervention non-compliance  
• 
If any clinical adverse event (AE), laboratory abnormality, or other medical condition or situation 
occurs such that continued participation in the study would not be in the best interest of the 
participant 
• 
Disease progression which requires discontinuation of the study intervention, such as: 
o Patient reaches ESRD and receives ongoing Hemodialysis/Peritoneal dialysis. 
o Patient receives kidney transplant 
• 
If the participant meets an exclusion criterion (either newly developed or not previously recognized)  
• 
Newly patient terminal illness diagnosis during the course of the study 
• 
If the participant changes their primary care provider to be outside of the health system 
 
While we do not anticipate provider initiated withdrawal of patient-participants, these events will be 
addressed on a case-by-case basis. 
 

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The reason for participant discontinuation or withdrawal from the study will be recorded on the 
“Reason for Withdrawal” Case Report Form (CRF) in REDCap. (Procedures for this will be included in the 
MOP) Subjects who have consented and are randomized but do not receive the study intervention may 
be replaced.  Subjects who have consented, and are randomized and receive the study intervention, and 
subsequently withdraw, or are withdrawn or discontinued from the study, will be replaced. 
 
 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if he or she fails to return for four scheduled research 
visits plus 4-6 health coaching calls and is unable to be contacted by the study site staff.  
 
The following actions will be taken if a participant fails to return to the clinic for a required study visit: 
• 
The site will attempt to contact the participant and reschedule the missed visit prior to the next 
scheduled study visit and counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain if the participant wishes to and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee will make every 
effort to regain contact with the participant (where possible, 3 telephone calls + emails, and, if 
necessary, a lost to follow up letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s study 
file.  
• 
Should the participant continue to be unreachable, he or she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up. 
 
8 
STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 
EFFICACY ASSESSMENTS  
 
8.1.1 PATIENT OUTCOME ASSESSMENT (AIM 2) 
 
Eligibility: All patients coming in for appointments at participating clinics will be screened for eligibility. 
Patients will be eligible if they are adults (21-85 years-old), have a diagnosis of hypertension and meet 
criteria of uncontrolled hypertension, have CKD stages 3–5, are not pregnant, and do not have cognitive, 
language, or vision impairments that would prohibit seeing the EDI or participating in coaching activities.  
 
Uncontrolled BP is defined as a systolic blood pressure >130 mmHg, and/or a diastolic blood pressure 
>80 mmHg noted in an ambulatory care setting within the past one year.  The University of Michigan has 
a registry of all patients within the system’s ambulatory clinics with CKD and hypertension. Through this 
registry we have found that a single, most recent BP correlates very closely with an average of the three 
most recent BPs taken within ambulatory clinics. Pregnant women with CKD have care goals that are 
unique compared to the general population with CKD and hypertension. Thus, their educational needs 
are outside the scope of this study and they will be excluded. 
 
Screening: We are working with UM and DMC/WSU IT to develop secure screening lists of eligible 
patients and for the ten sites. These lists will likely be generated on the order of weeks prior to the 
scheduled appointments. The study team will obtain approval from the provider before approaching the 
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be used for patients with CKD. However, the study team will not implement a BPA without obtaining 
approval from the IRB first. 
 
Quality initiative to improve CKD education: Prior to recruitment, patients at the control clinics will get 
a generic Control-EDI from their provider with CKD educational resources. Patients at the intervention 
clinics will review a pilot-tested Intervention-EDI with their provider in clinic, and receive a printed 
version at check out. This Intervention-EDI will cover basic CKD knowledge as well as review their recent 
lab results. Patients in the control clinic will just receive a generic Control-EDI about CKD. Copies of each 
handout are to be included in the MOP.  
 
Recruitment and study procedures: After patients check out, a study team member will approach them 
for recruitment. A pre-screening script will be used to ensure that the RA does not ever inform the 
patient of their CKD diagnosis. As stated above, up to 80% of people seen by primary care doctors do 
not know they have CKD. If the patient consents to be in the study, the first research survey will be 
administered and their BP and blood and urine specimens collected.  
 
For the intervention group, a health coach will call the patient approximately within one week of 
enrollment to obtain coaching baseline survey measures. Between the time of enrollment and 11 
months after enrollment, the health coach will schedule 4-6 coaching calls with the patient depending 
on their needs and availability.  
 
Both groups will have follow-up visits scheduled with the study team at approximately 1, 6, and 12 
months after enrollment to obtain research survey measures and BP. These visits will either take place 
at their original clinic, at other on-site clinic visits within the health system, at core lab facilities at UM 
for UM clinics that are not set up to offer research activity space on premises, or over the phone. When 
follow-up visits take place in person, we will find a private space to work with the participant. At the last 
patient study visit, blood and urine samples will be collected along with final surveys. We will allow 
some flexibility with the time points to accommodate the schedules of patients. A project flow diagram 
and schedule of activities are included in sections, 1.2 and 1.3 respectively.  
 
The specific outcomes of interest are in appendices, section 10.5. Efficacy of the study is primarily based 
on examination of whether patient CKD-specific education and subsequent health coaching improves 
systolic blood pressure compared to patients who only receive general kidney information and no health 
coaching. Additional clinical and patient reported measures will be assessed as time points along the 
study and at study conclusion to determine efficacy of the intervention on additional clinical and 
behavioral/knowledge outcomes important to patients.  
 
8.1.2 IMPLEMENTATION OUTCOME ASSESSMENT (AIM 3) 
 
Aim 3 of the study aims to examine whether and to what extent implementation outcomes (provider 
adoption, fidelity, and perceived usefulness) are associated with clinical and patient-reported outcomes. 
The participants will be primary care providers who has allowed the study team to screen their patients 
for eligibility and approach for recruitment in the study.  
 
Provider adoption will be assessed through several methods: (1) a provider survey, (2) patient surveys 
incorporating a question regarding whether the EDI was used during their visit, which has been 
completed in Aim 2, and (3) an EMR query to check if the EDI was populated into the patient’s EMR, or 
via research staff for instances where the EDI was used in its paper format in the clinic.  

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Provider fidelity to the EDI will be measured by checking if the provider entered 1-2 additional 
messages as recommended (queried through the EMR), or by observation during face-to-face 
encounters when using the paper version.  
 
Provider perceived usefulness of the intervention will be evaluated using specific questions included in 
the provider survey.  
 
The provider survey will be distributed via email, mail, or in person at the clinics. We will primarily 
contact these providers through their work emails. If they have left the health system, we will use the 
alternative email addresses or mailing addresses they provided. 
 
Additionally, as an exploratory outcome, health coach perceptions of the intervention will be assessed 
as part of the implementation outcome evaluation. Health coaches involved in delivering the 
intervention will be asked to complete an open-ended survey to share their experiences, aiming to 
identify areas for refinement and inform future implementation strategies. The health coach survey will 
be distributed via email. 
 
 
8.2 
SAFETY AND OTHER ASSESSMENTS 
A Data Safety and Monitoring Plan will be put into place as an integral part of the study’s manual of 
procedures—to monitor patient safety and evaluate the ability of the investigators to conduct the 
proposed study with utmost regard for patient / provider protection and confidentiality. The study will 
not begin without approvals of the University of Michigan IRB, as well as any local IRBs (DMC/WSU). The 
PI and study team will conduct periodic reviews of regulatory requirements.  
 
In addition, in accordance with federal regulations, the Data Safety and Monitoring Study Board will 
convene to act in an advisory capacity to the study and NIH NIDDK to monitor patient safety and 
evaluate the ability of the investigators to conduct the proposed research with utmost regard for patient 
protection and confidentiality.  The DSMB will undertake the following tasks:  
 
1. Approve initiation of the proposed study prior to study enrollment. 
2. Review the research protocol, informed consent documents, and plans for data safety and 
monitoring. 
3. Evaluate the progress of the study including periodic assessments of data quality and timeliness, 
participant recruitment, accrual and retention, participant risk versus benefit, performance of the 
clinical centers, and other factors that may affect study outcomes. This will occur at a minimum at the 
study initiation, when enrollment is ~25% complete, ~50% complete and 100% complete. Additionally, if 
the study is slow to recruit the DSMB will meet at least yearly.  
4. Consider factors external to the study when relevant information becomes available, such as scientific 
or therapeutic developments that may have an impact on the safety of the participants or the ethics of 
the study.  
5. Protect the safety of the study participants. 
6. Report on the safety and progress of the study. 
7. Make recommendations to the study team and NIH NIDDK, and if required, to the IRBs concerning 
continuation, termination or other modifications of the study based on the observed beneficial or 
adverse effects of the study procedures. 

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8. Review interim analysis in accordance with stopping rules that will be developed for the study 
protocol and that will be defined in advance of data analysis and have approval of the DSMB. 
9. Ensure the confidentiality of the study data and the results of monitoring. 
10. Assist the funding agency by commenting on any problems of study conduct, enrollment, sample 
size, and / or data collection. 
 
All aspects of the proposed research will be conducted with utmost regard for the welfare and privacy of 
the volunteer participants.  The DSMB meetings shall be closed to the public because discussions may 
address confidential patient data. Urgent or emergent meeting of the DSMB may be called at any time 
by the Chair of the DSMB or by the NIH Project Officer in the event of issues regarding patient safety. 
The format for the DSMB meetings may be open or closed as dictated by the agenda of the meeting.  
 
Termination of the Study: A majority vote of the DSMB will be required to issue a study termination 
recommendation. Potential reasons could be but are not limited to: 
1. An exceedingly large number of serious and unexpected adverse events. 
2. Severe and not rectifiable logistical or data quality problems. 
 
The DSMB will consist of selected members who are external to the study and who have no conflicts of 
interest or scientific involvement with the study. The DSMB will be lead / chaired by a Dr. T. Alp Ikizler 
M.D. He has served on other DSMBs and is both a clinical leader and well-established researcher. As 
needed, the PI and study biostatistician will be available to provide input and/or attend the DSMB’s 
meetings, at request of DSMB. 
 
In addition, any data integrity and patient safety-related issues will be prioritized. At study start, all 
research personnel, coaches and staff will undergo training and in-service meetings about study 
procedures. The importance of data security and compliance with procedures will be emphasized. All 
study personnel are required to complete and be certified by the Program for Education and Evaluation 
in Responsible Research and Scholarship (PEERRS) at the University of Michigan every 3 years (or 
equivalent, i.e. CITI training as applicable depending on University/site affiliation). A standard reporting 
form for adverse events will be created and completed by study personnel on an as-needed basis. 
Adverse events will be discussed at biweekly team meetings or sooner if needed and reported to the 
IRB. Documentation of completion of tasks and DSMB activities will be filed in the Regulatory Binder. 
The binder will also contain all communications to the IRB, including the initial application, study 
protocol, any amendments, annual IRB renewal, IRB approvals, and a summary of adverse events. It will 
be the responsibility of the project team to maintain and update the Regulatory Binder. In addition, the 
Project Manager/Coordinator will review consent forms, and source data at regular intervals along the 
study, with reviews documented in a Monitoring Log, accompanied by a Monitoring Report, which will 
be filed in the Regulatory Binder. 
 
Lastly, this project includes an applicable clinical trial that will be registered with ClinicalTrials.gov. 
   
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.3.1 DEFINITION OF ADVERSE EVENTS (AE) 
According to the UM Medical School Office of Research definition, an adverse event (AE) is any 
experience or abnormal finding that has taken place during the course of a research project and was 

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harmful to the subject participating in the research, or increased the risks of harm from the research, or 
had an unfavorable impact on the risk/benefit ratio. 
 
8.3.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
An adverse event (AE) or suspected adverse reaction is considered “serious” if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse 
event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the participant and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or drug abuse. 
 
8.3.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.3.3.1 SEVERITY OF EVENT 
According to the UM eResearch definition, adverse events are categorized according to the following 
grading system: 
 
0 – No adverse event 
1 – Mild AE – No treatment needed 
2 – Moderate AE – Resolved with treatment 
3 – Severe AE – Inability to carry on normal activities, required professional medical attention 
4 – Life-threatening or disabling AE 
5 – Fatal AE 
 
8.3.3.2 RELATIONSHIP TO STUDY INTERVENTION 
We will use the following levels of relationship to study intervention, which is in accordance to 
eResearch: 
 
• 
Definitely Related – There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test 
result, occurs in a plausible time relationship to study intervention administration and cannot be 
explained by concurrent disease or other drugs or chemicals. The response to withdrawal of the 
study intervention (dechallenge) should be clinically plausible. The event must be 
pharmacologically or phenomenologically definitive, with use of a satisfactory rechallenge 
procedure if necessary. 
• 
Probably Related – There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely. The clinical event, including an abnormal laboratory test result, occurs within 
a reasonable time after administration of the study intervention, is unlikely to be attributed to 
concurrent disease or other drugs or chemicals, and follows a clinically reasonable response on 
withdrawal (dechallenge). Rechallenge information is not required to fulfill this definition. 
• 
Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the trial medication). However, other 
factors may have contributed to the event (e.g., the participant’s clinical condition, other 

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concomitant events). Although an AE may rate only as “possibly related” soon after discovery, it 
can be flagged as requiring more information and later be upgraded to “probably related” or 
“definitely related”, as appropriate. 
• 
Unlikely to be related – A clinical event, including an abnormal laboratory test result, whose 
temporal relationship to study intervention administration makes a causal relationship 
improbable (e.g., the event did not occur within a reasonable time after administration of the 
study intervention) and in which other drugs or chemicals or underlying disease provides 
plausible explanations (e.g., the participant’s clinical condition, other concomitant treatments). 
• 
Not Related – The AE is completely independent of study intervention administration, and/or 
evidence exists that the event is definitely related to another etiology. There must be an 
alternative, definitive etiology documented by the clinician.] 
 
8.3.3.3  EXPECTEDNESS  
The principal investigator will be responsible for determining whether an adverse event (AE) is expected 
or unexpected.  An AE will be considered unexpected if the nature, severity, or frequency of the event is 
not consistent with the risk information previously described for the study intervention. It is important 
to note in this population of patients with moderate to severe kidney disease AND uncontrolled high 
blood pressure, that they are already at high risk compared to the general population of the following: 
• 
Cardiovascular and cerebrovascular events (e.g. heart attack, congestive heart failure, stroke) 
• 
Complications from CKD itself that are expected and a part of CKD (especially in more advanced 
CKD): 
o Hematologic problems e.g. anemia, low counts of cells if on immune suppression 
o Any infection because of immune suppressed state in chronic disease or medications 
o Bone and mineral problems e.g. with calcium, phosphorus in blood, stones, bone 
fractures, hyperparathyroidism 
o Cardiac arrythmias 
o Flank pain from stones, cysts, or that can occur in certain types of CKD e.g. due to IgA 
nephropathy 
o Fatigue and being tired 
• 
Complications related to often-times related co-morbid conditions, e.g. diabetes with high or 
low blood sugar, retinopathy, neuropathy 
• 
Progression of kidney disease to end stage renal failure 
• 
Weight gain or weight loss due to kidney disease or co-morbid conditions 
• 
Exposure to medications that can result in hypotension, muscle breakdown, syncope, leg 
swelling, drug-drug interactions, and electrolyte imbalances/which can sometimes be severe 
and even fatal 
• 
Exposure to medications that can cause or be related to cancer or increase risk of cardiovascular 
events or infection (immune suppressive therapies) 
• 
Electrolyte imbalances due to their kidney disease 
• 
Infection due to immune suppression associated with kidney disease and/or medications used 
to manage kidney disease 
• 
Difficulty coping with multiple co-morbid conditions and sometimes even depression 
• 
Psychosocial difficulties 
• 
Difficulty breathing, with shortness of breath 
• 
Scheduled surgery or procedures or post-operative complications 
• 
Common conditions in older adult population e.g. fall, altered mental status, syncope 
• 
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As such, these events are expected in this population regardless of whether or not they receive CKD-
education and health coaching, and it would not be considered unusual for any of these events to occur 
in this population during the course of the study.  However, these potential expected and unexpected 
risks will be outlined for patients in the informed consent document(s). 
 
The definitions from eResearch on expectedness is as follows: 
 
• 
Unexpected adverse events (i.e., has NOT been addressed or described in one or more of the 
following: Informed consent document(s) for this study, IRB application for this study, grant 
application or study agreement, protocol or procedures for this study, investigators’ brochure or 
equivalent (for FDA regulated drugs or devices), DSMB/DSC Reports, published literature, other 
documentation) 
• 
Expected adverse events (i.e., has been addressed or described in one or more of the following: 
Informed consent document(s) for this study, IRB application for this study, grant application or 
study agreement, protocol or procedures for this study, investigators’ brochure or equivalent 
(for FDA regulated drugs or devices), DSMB/DSC Reports, published literature, other 
documentation, or characteristics of the study population)  
8.3.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may come to the attention of 
study personnel during study visits and interviews of a study participant presenting for medical care, or 
upon review by a study monitor. 
 
All Aes including local and systemic reactions not meeting the criteria for SAEs will be captured on the 
appropriate case report form (CRF). Information to be collected includes event description, time of 
onset, clinician’s assessment of severity, relationship to study product (assessed only by those with the 
training and authority to make a diagnosis), and time of resolution/stabilization of the event. All Aes 
occurring while on study must be documented appropriately regardless of relationship. All Aes will be 
followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened will be considered as 
baseline and not reported as an AE. However, if the study participant’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the event 
at each level of severity to be performed. Aes characterized as intermittent require documentation of 
onset and duration of each episode. 
 
The study team will record all reportable events with start dates occurring any time after informed 
consent is obtained until 7 (for non-serious Aes) or 30 days (for SAEs) after the last day of study 
participation.  At each study visit, the investigator will inquire about the occurrence of AE/SAEs since the 
last visit.  Events will be followed for outcome information until resolution or stabilization.  
 
8.3.5 ADVERSE EVENT REPORTING  
We will report all adverse event according to the UM Medical School Office of Research reporting 
timetable: 

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8.3.6 SERIOUS ADVERSE EVENT REPORTING  
We will report serious adverse events according to the Office of Research timetable above. DSMP/DSMB 
described in section 8.2. We do not anticipate any study-related serious adverse events to occur as this 
is a study with no more than minimal risk. 
  
8.3.7 REPORTING EVENTS TO PARTICIPANTS  
Not applicable – Any adverse events that may happen will likely be due to individual differences, e.g. 
baseline health status, instead of systemic issues. 
 
8.3.8 REPORTING OF PREGNANCY  
Pregnancy is an exclusion criteria for our study. Within the informed consent form we will include a 
statement that should a patient become pregnant they must withdraw, in line with procedures stated 
above in section 7.2.  An additional statement will be included to explain why pregnancy is an exclusion 
criteria, specifically, because the CKD education and health coaching needs of women with high blood 
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self-care needs to be carefully led and guided by specialist providers (e.g. maternal fetal medicine 
doctors).  
 
8.4 
UNANTICIPATED PROBLEMS 
 
8.4.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
The Office for Human Research Protections (OHRP) considers unanticipated problems involving risks to 
participants or others to include, in general, any incident, experience, or outcome that meets all of the 
following criteria: 
 
• 
Unexpected in terms of nature, severity, or frequency given (a) the research procedures that are 
described in the protocol-related documents, such as the Institutional Review Board (IRB)-
approved research protocol and informed consent document; and (b) the characteristics of the 
participant population being studied; 
• 
Related or possibly related to participation in the research (“possibly related” means there is a 
reasonable possibility that the incident, experience, or outcome may have been caused by the 
procedures involved in the research); and 
• 
Suggests that the research places participants or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or recognized. 
 
8.4.2  UNANTICIPATED PROBLEM REPORTING  
According to UM Medical School Office of Research guidelines: 
Serious unanticipated problems and Unanticipated Adverse Device Effects (UADEs) must be reported 
within 7 calendar days of the problem (or within 7 calendar days of the study team becoming aware of 
the problem). Non-serious unanticipated problems must be reported within 14 calendar days of the 
problem (or within 14 calendar days of the study team becoming aware of the problem). 
 
If the unanticipated problem involved one or more persons experiencing actual harm, report the 
unanticipated problem as an adverse event. Refer to the AE Reporting page 
(https://az.research.umich.edu/medschool/guidance/adverse-event-reporting) and follow the 
instructions provided, using the external or internal form as appropriate. 
 
If a person did not experience actual harm but an unanticipated problem entailed potential harm, 
and/or risk of harm to subjects or others, refer to the ORIO Reporting page 
(https://az.research.umich.edu/medschool/guidance/other-reportable-information-or-occurrence-orio) 
and follow the instructions provided. 
 
If the IRB concurs that an event is an unanticipated problem the study team will follow the policies and 
procedures outlined in the University of Michigan Human Research Protection Plan Operations Manual, 
part 12. 
 
8.4.3 REPORTING UNANTICIPATED PROBLEMS TO PARTICIPANTS  
N/A 
 
 
 
 

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9 
STATISTICAL CONSIDERATIONS  
 
9.1 
STUDY HYPOTHESES 
Study hypotheses are aligned with our study aims. All aims related to this study are outlined below, 
and separate sub-studies are noted, where applicable. 
 
Aim 1: Optimize the process of delivering a provider-led, coach-supported patient education 
intervention prior to using it in a cluster-randomized controlled trial. We will use CQI and systems 
improvement methods, with input from multi-disciplinary teams, to streamline how the provider-
delivered EDI will be integrated into clinics. [This aim and its activities are covered with a separate but 
related QI IRB approved study – HUM00152989.] We hypothesize that: H1. CQI and systems approaches 
will facilitate resource and process efficiency comparing intervention and control groups. 
 
Aim 2: Identify the impact of a provider-led, coach-supported patient education intervention on 
patient clinical and self-reported outcomes over one year using a cluster-randomized controlled trial. 
The primary outcome is change in systolic blood pressure between T0 and T3, and the secondary 
outcomes are slope of systolic BP between all timepoints, change and slope in diastolic blood pressure 
between all timepoints, estimated glomerular filtration rate (EgfR), urine protein:urine creatinine, serum 
creatinine, medication adherence, patient knowledge, self-efficacy, motivation, and satisfaction. We 
hypothesize that, compared to patients in the control group, patients in the intervention group will: H2.  
Have lower blood pressure. H3. Experience higher EgfR, greater reductions in urine protein, and higher 
medication adherence. H4. Have greater knowledge about CKD, and higher self-efficacy, motivation, and 
satisfaction with CKD care. 
 
Aim 3: Identify whether and to what extent implementation outcomes (provider adoption, fidelity, 
perceived usefulness) are associated with clinical and patient-reported outcomes. We hypothesize 
that: H5. Within intervention clinics, provider adoption, perceived usefulness of, and fidelity to the 
provider-delivered Intervention-EDI will be high and positively associated with clinical and patient-
reported outcomes. H6. Providers will perceive the intervention as beneficial and feasible for future 
translation into community settings. 
 
9.2 
SAMPLE SIZE DETERMINATION 
 
The primary outcome is 
systolic BP. A conservative 
difference of systolic BP 
between intervention and 
control groups ranges from 
3–5 mmHg.72-76 It is assumed 
that each patient will have BP 
checked at least four times in 
person. Additional clinical BPs 
in the EMRs, including those 
used by various specialties 
within the health system, will be recorded as available. Sample size calculations are based on a 
comparison of intervention and control groups in baseline minus 12 month differences in a cluster-

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randomized controlled trial. A significance level of 0.05, power of 0.90, and a standard deviation of 7 for 
the between-patient variation in baseline minus 12 month differences were assumed in all 
calculations.77  Based on prior studies, the intraclass correlation coefficient (ICC) for clinics is likely to be 
0.10 or lower.78 The table above gives the total number of clinics required to detect a difference 
between groups of 3–5 mmHg with 90% power for ICCs of 0.05, 0.10, and 0.15, and 30, 50, or 100 
patients per clinic. Based on these power calculations, balancing rigor and efficiency, 9.4 clinics (rounded 
to 10) are needed if we recruit 30 patients at each clinic, to detect a difference of 4 mmHg between the 
intervention and control group clinics with an ICC of 0.10. Recruiting up to 50 or even 100 patients does 
not significantly change the number of clinics needed. We have commitment from 10 participating 
clinics, allowing an equal number in each treatment group and giving us ample power to detect 
differences in the primary outcome. Enrolling 30 patients per clinic in 10 clinics yields a total patient 
enrollment of 300. However, prior similar studies show there may be patient withdraws of up to 10-
15%.11 We will increase the target enrollment number for the participating clinics (for up to 10 
participants per clinic) where we are able to recruit more and if/when there is higher than 10-15% drop 
out. We will also add clinics (for up to 5 clinics) as supplementing clinics for clinics that are not on track 
of enrolling at least 15 participants. As such we will increase enrollment targets to a total of 450 
patients. 
 
9.3 
POPULATIONS FOR ANALYSES 
For the primary outcome (12-month systolic BP), an intention-to-treat analysis will be used, with 
treatment (intervention) effects tested in the initial models described for cluster-randomized trials with 
pre-planned covariates.79 If a clinic drops out of the study prior to patient enrollment, we will consider 
asking other clinics at study sites to participate as alternatives. If a clinic drops out after study 
enrollment commences (which we do not expect, as shown in letters of support), they will be analyzed 
as intention-to-treat. Clinical trial analyses often are limited to those patients with complete data. 
However, this strategy may yield overly optimistic effect size estimates since problems adhering to the 
protocol or worse health status often are associated with missing data. Although we will conduct an 
initial analysis using only observed data, we will conduct a second analysis that imputes missing data for 
patients using the method described by Lavori, Dawson, and Shera.80 In brief, we will use logistic 
regression to model patients’ or clinics’ likelihood of having outcome data and define strata within 
which outcome values are missing at random. We will then stratify according to these propensities, 
randomly sample from the observed outcome distribution, and impute these values for missing data 
within each stratum. When data are missing for items within survey scales, we will use recommended 
imputation procedures rather than deleting patients list-wise from the analysis.81    
 
9.4 
STATISTICAL ANALYSES 
 
9.4.1 GENERAL APPROACH 
We will follow international guidelines for analysis and reporting of cluster-randomized clinical trials.79  
We will first examine the distributions of all study variables to assess missing data, possible coding 
errors, and distributional form, including skewness, variance, and extreme values. Next, we will explore 
bivariate associations between study variables. We will examine baseline data for clinically important 
differences between treatment groups for demographics and clinical data, including BP and other 
potential prognostic indicators, at the patient level. 
 
 
 

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9.4.2 ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT(S) 
For the primary outcome (12-month systolic BP), an intention-to-treat analysis will be used, with 
treatment (intervention) effects tested in the initial models described for cluster-randomized trials with 
pre-planned covariates.79 Systolic BP is continuous and analysis requires accommodating correlation 
within clinics, so we will use linear mixed models with a random effect for clinic implemented using the 
MIXED procedure in SAS. The baseline systolic BP will be included as a covariate. Two secondary 
analyses will be performed. First, the within-person slope of systolic BP over time will be modeled, using 
all time points including baseline as outcomes, with an interaction between intervention and control 
groups and time included to test for different slopes between intervention and control groups. Second, 
baseline covariates that significantly differ between treatment groups will be included as covariates in 
models comparing treatment groups. Diastolic BP is inherently measured with systolic BP and is also a 
continuous measure. We will examine differences in diastolic BP in secondary analyses, similarly as 
described for systolic BP. 
 
9.4.3 ANALYSIS OF THE SECONDARY ENDPOINT(S) 
Although the study was not powered specifically for secondary outcomes, the majority of the secondary 
outcomes are continuous variables (time patients spend in clinic visit at t(0), EgfR, urine protein, as well 
as most survey measures, including but not limited to: patient knowledge, medication adherence, self-
efficacy, motivation, and satisfaction. For more details, please see Appendix 1.) for which power can be 
calculated based on effect sizes (multiples of the standard deviation) for any specific outcome. With the 
original target, a total of 350 patients (175 in the intervention and control group each), we have a 90% 
power to detect an effect size of 0.4 assuming an ICC of 0.10 within cluster. This is a small to moderate 
effect on Cohen’s scale where approximately 0.25 is a small effect and 0.50 is moderate. We will try to 
achieve the same overall power by adding patients at clinics where we are able to recruit more and 
if/when there is higher than 10-15% drop out. We will also add clinics (for up to 5 clinics) as 
supplementing clinics for clinics that are not on track of enrolling at least 15 participants.  
As above, for continuous data, analysis requires accommodating correlation within clinics, so we will use 
linear mixed models with a random effect for clinic implemented using the MIXED procedure in SAS to 
test the treatment (intervention) impact on outcome. The respective baseline continuous measure will 
be included as a covariate in each model. For Aim 1 hypothesis testing (whether delivery of EDI is 
efficient), the time patients spend in clinic at visit t(0), is only a one-time, baseline comparison.     
 
9.4.4 SAFETY AND INTERIM ANALYSES 
Safety monitoring, classification of events and reporting are described in section 8. There are no planned 
interim analyses other than what is done for study data safety and monitoring along enrollment for the 
study. When enrollment is 25% complete, 50% complete, and 100% complete, the following will be 
collected and analyzed descriptively and reviewed by the study DSMB: 
• 
Number screened, number enrolled, number withdrawn. 
• 
Demographics for patients enrolled in control and intervention clinics. 
• 
Adverse events analysis which will include descriptive analyses of the adverse event, severity, 
whether unexpected or expected, whether or not there were associated hospitalizations.  
 
9.4.5 BASELINE DESCRIPTIVE STATISTICS 
For outcomes that are categorical (e.g. provider adoption of, and fidelity to, the EDI, EMR medication 
refills and exploratory analyses related to patient behaviors in the past week), we will test intervention 
effects using logistic regression for longitudinal data (SAS Genmod or Glimmix procedure).  When 
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EgfR, Urine protein) and patient-reported (patient knowledge, medication adherence, self-efficacy, 
motivation, and satisfaction) outcomes, analysis will be limited to the clinics assigned to intervention.  
We will use surveys that are previously validated where able (e.g. CKD knowledge survey by Wright et 
al.25). For surveys that are new or adapted for this study, we will examine for evidence of reliability and 
validity. Specifically, Cronbach’s alpha (or Kuder Richardson-20 ) will be used to quantify internal 
consistency among items. We will use principal component factor analysis to characterize clustering of 
items and potential sub-scales.82 We will evaluate for evidence of validity comparing correlation to 
original scales when surveys are adapted, or to examine for expected associations with measured 
characteristics when no prior scales have been developed. To detect associations between the survey 
scales and measured characteristics (e.g. patient sex, age) chi-square tests, t-tests, and Kruskal-Wallis 
tests will be used depending on the variables compared.  
 
9.4.6 TABULATION OF INDIVIDUAL PARTICIPANT DATA 
Individual participant data will not be listed by measure and time point except for safety monitoring and 
interval DSMB reporting— and then only as aggregate and not identifiable, as outlined in section 8 and 
included in the MOP.  
 
9.4.7 EXPLORATORY ANALYSES 
Cost-effectiveness of coaching: A key to the sustainability of our intervention is to understand the cost 
of the intervention versus potential cost saving from lowering the rate of use of other resources (e.g. ER 
or hospital visits). A formal cost-effectiveness modeling exercise is beyond the scope of this study, but 
we will examine annual costs of coaches’ actual clinical work, so that a formal cost-effectiveness 
assessment can be performed in future next steps. We will do this by tracking the hours necessary for 
coaches’ clinical work (i.e. time spent coaching patients, not research-related activities) using time logs. 
We will then estimate the annual patient volume for each coach and account for the costs of the coach 
using their pay scale broken down into an hourly wage. In next steps, cost savings will be estimated by 
examining the differential in use in patient resources (e.g. inpatient hospitalizations, ER visits) between 
groups. Similar approaches have been used previously.83 
 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
 
10.1.1 INFORMED CONSENT PROCESS 
 
10.1.1.1 CONSENT/ASSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO 
PARTICIPANTS 
Consent will be obtained through one of two methods: The preferred method is in-person, with a 
signature obtained on a paper version of the informed consent. If the patient cannot stay after their 
appointment, they will be given the option to complete the consent process through phone. Instead of a 
signature, they will be asked if they agree to be in the study. Answering “yes” to that question indicates 
consent to enroll in the study. If the patient is consented on the phone, they will be given a copy of the 
consent form (hard copy) for their personal records. The consent form describes in detail the study 
intervention, study procedures, risks and benefits, and contact information for the study team. Copy of 

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the consent forms (one for patients enrolled to serve as controls and other for patients enrolled to 
receive intervention) are uploaded in eResearch. 
 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. The preferred method of informed 
consent is in-person. However, if the patient cannot stay after their appointment, we will give them the 
option to consent over the phone. 
 
In-person consent: 
Consent forms will be Institutional Review Board (IRB)-approved and the participant will be asked to 
read and review the document. The study team member will explain the research study to the 
participant and answer any questions that may arise. A verbal explanation will be provided in terms 
suited to the participant’s comprehension of the purposes, procedures, and potential risks of the study 
and of their rights as research participants.  Participants will have the opportunity to carefully review the 
written consent form and ask questions prior to signing.  
 
Phone consent: 
A study team member will go through the Institutional Review Board (IRB)-approved consent form 
content on the phone with the patient. The study team member will explain the research study to the 
participant and answer any questions that may arise. A verbal explanation will be provided in terms 
suited to the participant’s comprehension of the purposes, procedures, and potential risks of the study 
and of their rights as research participants.  Participants will have the opportunity to ask questions prior 
to verbally consenting. The patient will be given a copy of the consent form (hard copy) for their 
personal records. 
 
The participant will sign/say yes to and complete the informed consent process prior to any procedures 
being done specifically for this study and activities that are not unregulated. Participants will be 
informed that participation is voluntary and that they may withdraw from the study at any time, without 
negative impact to them (without prejudice). A copy of the informed consent document will be given or 
sent to the participants for their records. The informed consent process will be conducted and 
documented in the source document (including the date), and the form signed, before the participant 
undergoes any study-specific procedures. The rights and welfare of the participants will be emphasized 
and consent will include a specific statement that the quality of their medical care will not be adversely 
affected if they decline to participate in this study.  
 
 
10.1.1.3 AIM 3 CONSENT PROCEDURES 
In Aim 3, participating primary care providers will receive a provider survey accompanied by an 
informed consent cover letter, available in electronic or paper format. This cover letter will explain the 
purpose of the study, the voluntary nature of participation, confidentiality measures, and contact 
information for the study team. Providers will provide consent by proceeding with the survey after 
reading this letter.  
 
Similarly, health coaches will receive an open-ended survey to share their perceptions of the 
intervention. An information sheet at the beginning of the survey will explain its purpose, the voluntary 
nature of participation, confidentiality measures, and contact information for the study team. Health 
coaches will indicate their consent by proceeding with the survey after reviewing this information. 

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10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause.  Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to study participants, investigator, funding agency, and 
regulatory authorities as appropriate.  If the study is prematurely terminated or suspended, the Principal 
Investigator (PI) will promptly inform study participants, the Institutional Review Board (IRB), and 
sponsor and will provide the reason(s) for the termination or suspension.  Study participants will be 
contacted, as applicable, and be informed of changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not limited to: 
• 
Determination of unexpected, significant, or unacceptable risk to participants 
• 
Demonstration of efficacy that would warrant stopping    
• 
Insufficient compliance to protocol requirements 
• 
Data that are not sufficiently complete and/or evaluable 
• 
Determination that the primary endpoint has been met 
• 
Determination of futility 
 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the sponsor, DSMB and IRB.  
 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, their 
staff, and the sponsor(s) and their interventions. This confidentiality is extended to cover testing of 
biological samples, patient-reported measures (either during coaches or study surveys) and clinical 
information relating to participants. Therefore, the study protocol, documentation, data, and all other 
information generated will be held in strict confidence. No information concerning the study or the data 
will be released to any unauthorized third party without prior written approval of the sponsor.  
 
All research activities will be conducted in as private areas. Coach calls will be direct to patients and 
arranged with patients prior, as appointments, so that patients are allowed to ensure they are available 
and in an appropriate setting to receive coach calls. 
 
The study monitor, other authorized representatives of the sponsor, representatives of the Institutional 
Review Board (IRB), or regulatory agencies may inspect all documents and records required to be 
maintained by the investigator, including but not limited to medical records (office, clinic, or hospital) 
and pharmacy records for the participants in this study. In this case the clinical study site will permit 
access to such records. 
 
The study participant’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the reviewing IRB, institutional policies, or sponsor requirements. 
 
The database that contains survey results and clinical data will only be identified by study ID’s. A 
separate file will be created to link the participant’s name and other identifiable data to the study ID. 
Only the core study team (e.g. PI and research assistants) will have access to the password protected 
linking file. We do not anticipate any information to be identifiable without the linking file. Only health 
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on patients receiving health coaching and that would only be in the case of logging into the secure 
password protected coach consul for study purposes and/or coaching (in cases for coaches). 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, will 
be transmitted to and stored at the University of Michigan. All transferred data will abide by local and 
UM policies regarding sharing data and encryption. The study data entry and study management 
systems used by clinical sites and by University of Michigan research staff will be secured and password 
protected. At the end of the study, all study databases will be de-identified and archived at the 
University of Michigan. 
 
Certificate of Confidentiality  
To further protect the privacy of study participants, a Certificate of Confidentiality will be issued by the 
National Institutes of Health (NIH).  This certificate protects identifiable research information from 
forced disclosure. It allows the investigator and others who have access to research records to refuse to 
disclose identifying information on research participation in any civil, criminal, administrative, legislative, 
or other proceeding, whether at the federal, state, or local level. By protecting researchers and 
institutions from being compelled to disclose information that would identify research participants, 
Certificates of Confidentiality help achieve the research objectives and promote participation in studies 
by helping assure confidentiality and privacy to participants. 
  
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
Biochemistry:  serum creatinine will be collected at the time of enrollment and at time of study 
completion (12 months post enrollment). This equates to 2 serum creatinine measurements per 
patient in total for the study. A total of about 8 tablespoons of blood will be collected from each 
participant (4 tablespoons once at enrollment plus 4 tablespoons at completion of the study). This 
equates to a total of about 120 ML of blood collected. This will be collected using existing local UM 
and DMC/WSU laboratory facilities for collection and processing, using their standardized assays. 
Previously established and local laboratory practices will be followed.  
 
Urine testing:  a urine protein measurement and a urine creatinine measurement will be collected 
at the time of enrollment and at study completion for the patient. This is to calculate urine protein 
to urine creatinine ratio. At least 10 ml will be collected and no more than 200 ml (it is difficult for 
patients to urinate a specific amount because the sample is collected into a small cup). This will be 
collected using existing local UM and DMC/WSU laboratory facilities for collection and processing, 
using their standardized assays. Previously established and local laboratory practices will be 
followed.  
 
10.1.5 KEY ROLES AND STUDY GOVERNANCE 
 
Principle Investigator:  
Julie A. Wright, MD MPH 
Associate Professor of Medicine 
Department of Internal Medicine, Division of Nephrology 
University of Michigan  
1500 E Medical Center Dr 
Taubman Health Center, RM 3914Ann Arbor, Michigan 48109 
734-764-5178 

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juwright@med.umich.edu 
 
Co-investigators: Jennifer Bragg-Gresham, PhD, Kristin Collier, MD, Audrey Fan, MD, Luis Garcia-
Guzman, PhD, Brenda Gillespie, PhD, Eve Kerr, MD, Kenneth Resnicow, PhD, Caroline Richardson, MD 
(currently affiliated with Brown University and emeritus faculty at the University of Michigan, Rajiv 
Saran, MBBS, DTCD, MD, MRCP, MS, Angela Fagerlin, PhD (subcontract through University of Utah), 
Diane Levine, MD (subcontract through Detroit Medical Center / Wayne State University), Emerson 
Delacroix, MACP, LLP, Shannon Considine, MSW, MPH 
 
10.1.6 SAFETY OVERSIGHT 
Safety oversight will be under the direction of a Data and Safety Monitoring Board (DSMB) composed of 
individuals with the appropriate expertise.  The DSMB will consist of selected members who are external 
to the study and who have no conflicts of interest or scientific involvement with the study. The DSMB 
will be lead / chaired by a Dr. T. Alp Ikizler M.D. He has served on other DSMBs and is both a clinical 
leader and well-established researcher. As needed, the PI and study biostatistician will be available to 
provide input and/or attend the DSMB’s meetings, at request of DSMB.  The DSMB will approve 
initiation of the proposed study for enrollment of human subjects, evaluate the progress of the study at 
initiation, when enrollment is 25% complete, 50% complete, and 100% complete.  Additionally, if the 
study is slow to recruit, the DSMB will meet at least yearly.  In addition, urgent or emergent meetings of 
the DSMB may be called at any time by the chair of the DSMB or NIH project officer in event of any 
issues regarding patient safety.  The DMSB will operate under the rules of an approved charter that will 
be written and reviewed at the organizational meeting of the DSMB.  At this time, each data element 
that the DSMB needs to assess will be clearly defined. DSMB reports will be included in status reports 
(RPPR reporting) to the NIH yearly.  
 
10.1.7 CLINICAL MONITORING 
To assure adequate protection of the rights of human subjects, Dr. T. Alp Ikizler, Professor of Medicine 
and Chief of the Division of Nephrology at Vanderbilt will chair the Data Safety Monitoring Board that 
will conduct monitoring of the study per a monitoring agreement to be included in the MOP. The 
established monitoring plan will ensure the quality and integrity of the data through pre-investigation 
visits, periodic site visits, review of adverse events/subject records, with recording of study progress in 
enrollment, demographics, and adverse events analyses in regularly scheduled reports.  
 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
To ensure consistent delivery of the intervention and uniform application of enrollment and data 
collection protocols, we hosted a kick-off meeting in Year 1 attended by investigators, research staff, 
project support and representatives from each site. Goals of the study were discussed along with design 
and procedures. Study team members have been split into teams and assigned aspects of the study to 
develop and give input on study materials development. In addition, we brought in experts in quality 
improvement (through UM Quality and Innovation Program) and leaders on the study team in 
continuous quality improvement (CQI). With study team member input, we have developed a study 
team communication plan for study personnel, staff, co-investigators, as well as providers and staff in 
involved clinics. We are working with staff at UM to develop an online project website, and there will be 
an additional secure/password protected feature for providers from involved clinics to sign in and learn 
more about the study. Descriptions of the study will be produced in a variety of formats for distribution 
via group emails and as handouts in clinic.  
 

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In addition, for specific study procedures, we will produce data collection manuals with detailed 
instructions for issues such as how to note missing data, how to make changes on data collection forms, 
and how to adjudicate decisions when survey response options are unclear and have this reviewed by 
our colleague experts in CQI. In addition, once enrollment begins, data quality issues will be discussed at 
weekly meetings between project staff and the PI. Data integrity and completeness will be checked 
periodically by research personnel and reported at biweekly team meetings as described previously in 
section 8.2. 
 
Quality control (QC) procedures will be implemented beginning with the data entry systems and data QC 
checks that will be run on the database will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
 
Following written Standard Operating Procedures (SOPs), the monitors will verify that the clinical trial is 
conducted and data are generated and biological specimens are collected, documented (recorded), and 
reported in compliance with the protocol, International Conference on Harmonisation Good Clinical 
Practice (ICH GCP), and applicable regulatory requirements (e.g., Good Laboratory Practices (GLP), Good 
Manufacturing Practices (GMP)).  
 
The investigational site will provide direct access to all trial related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the sponsor, and inspection by local and 
regulatory authorities. 
 
Rigor and reproducibility will be maximized by quality control of all study protocols and procedures and 
by using a robust experimental design for the intervention. This study applies high standards in its 
methodology and its analysis plan which will be continued through interpretation and results reporting. 
We will be transparent in reporting experimental details so that others may reproduce and extend the 
findings in the future. 
 
10.1.9 DATA HANDLING AND RECORD KEEPING  
 
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
 
All source documents should be completed in a neat, legible manner to ensure accurate interpretation 
of data.   
 
Hardcopies of the study visit EDIs will be provided for use as source document EDIs for recording data 
for each participant enrolled in the study.  Data recorded in the electronic case report form (EcrF) 
derived from source documents should be consistent with the data recorded on the source documents.  
 
Clinical data (including adverse events (Aes), concomitant medications, and expected adverse reactions 
data) and clinical laboratory data will be entered into REDCap, a 21 CFR Part 11-compliant data capture 
system provided by the University of Michigan. The data system includes password protection and 
internal quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered directly from the source documents. 
 
10.1.9.2 STUDY RECORDS RETENTION  
 

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Study documents will be retained for a minimum of 2 years after the last approval of a marketing 
application in an International Conference on Harminosation (ICH) region and until there are no pending 
or contemplated marketing applications in an ICH region or until at least 2 years have elapsed since the 
formal discontinuation of the study intervention. These documents should be retained for a longer 
period, however, if required by local regulations. No records will be destroyed without the written 
consent of the sponsor, if applicable. It is the responsibility of the sponsor to inform the investigator 
when these documents no longer need to be retained. 
 
10.1.10 
PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical trial protocol, International Conference on 
Harmonisation Good Clinical Practice (ICH GCP), or Manual of Procedures (MOP) requirements. The 
noncompliance may be either on the part of the participant, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly.  
 
These practices are consistent with ICH GCP:  
• 
4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 
5.1 Quality Assurance and Quality Control, section 5.1.1  
• 
5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and report 
deviations.  All deviations will be addressed in study source documents, reported to the NIH NIDDK 
Program Official and University of Michigan Institutional Review Board (IRB). The site investigator is 
responsible for knowing and adhering to the reviewing IRB requirements.  
 
10.1.11 
PUBLICATION AND DATA SHARING POLICY 
 This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the public has access to the 
published results of NIH funded research. It requires scientists to submit final peer-reviewed journal 
manuscripts that arise from NIH funds to the digital archive PubMed Central upon acceptance for 
publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded 
Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. As 
such, this trial will be registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish results in peer-
reviewed journals.  Data from this study may be requested from other researchers years after the 
completion of the primary endpoint by contacting Julie Wright, MD, MPH. 
 
In addition, this study will comply with the NIH Genomic Data Sharing Policy, which applies to all NIH-
funded research that generates large-scale human or non-human genomic data, as well as the use of these 
data for subsequent research. This study protocol however does not involve the collection and sharing of 
genomic data. 
 
10.1.12 
CONFLICT OF INTEREST POLICY 
 

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The independence of this study from any actual or perceived influence, such as by the pharmaceutical 
industry, is critical.  Therefore, any actual conflict of interest of persons who have a role in the design, 
conduct, analysis, publication, or any aspect of this trial will be disclosed and managed. Furthermore, 
persons who have a perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial.  The study 
leadership in conjunction with the NIH NIDDK and UM and DMC/WSU have established policies and 
procedures for all study group members to disclose all conflicts of interest and will establish a 
mechanism for the management of all reported dualities of interest. 
 
10.2 ADDITIONAL CONSIDERATIONS 
Not applicable. 
 

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10.3 ABBREVIATIONS 
 
AE 
Adverse Event 
BP 
Blood pressure 
CFR 
Code of Federal Regulations 
CHECK-D 
Controlling Hypertension through Education and Coaching in Kidney Disease 
CKD 
Chronic kidney disease 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT 
Consolidated Standards of Reporting Trials 
CQI 
Continuous quality improvement 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DMC/WSU Detroit Medical Center/Wayne State University 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
EcrF 
Electronic Case Report Forms 
EDI 
Encounter decision intervention 
EGFR 
Estimated glomerular filtration rate 
ESRD 
End stage renal disease 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act  
HTN 
Hypertension 
ICH 
International Conference on Harmonisation  
IRB 
Institutional Review Board 
MOP 
Manual of Procedures 
NCT 
National Clinical Trial 
NIH  
National Institutes of Health 
PI 
Principal Investigator 
QC 
Quality Control 
QI 
Quality improvement 
RA 
Research assistant / research associate 
SAE 
Serious Adverse Event 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOP 
Standard Operating Procedure 
UM 
University of Michigan 
UP 
Unanticipated Problem 
US 
United States 
 
 
 

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10.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the protocol, including a 
description of the change and rationale. A Summary of Changes table for the current amendment is 
located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
V.0.2 
03/14/2019 
V.0.1 submitted to UM-IRB on 
January 4, 2019. After initial 
review, IRB requested multiple 
revisions including: 
 
1) Educational worksheet/tool is 
now referred to as the Control-
EDI or Intervention-EDI 
2) Health coaching website is 
now referred to as the portal 
3) Removed mentioning of HUM 
155950 – study team was 
advised by IRB to not submit 
EDI as a QI project, but rather 
part of this study – 
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4) We are no longer using the 
Central Biorepository 
 
Requested by IRB and to keep 
terminology consistent. 
 
V.0.2 approved by IRB on 
03/27/2019. 
 
V.1.0 
06/19/2019 
1) Expanded criteria for early 
withdrawal/discontinuation of 
patient-participants  
2) Added “terminal illness” as 
exclusion criteria 
3) Addition of PI signature page 
4) Minor text corrections 
1) To more precisely define 
events that would warrant 
ending subject participation 
2) It is not the intent of the study 
to recruit terminally ill patients  
3) To meet GCP requirements 
 
V.1.0 approved by IRB on 
08/05/2019. 
 
V1.1 
10/04/2019 
1) Updated outcome measures to 
reflect changes made during 
ClinicalTrials.gov review (see 
Sections 1.1, 3, 6.1, 9.1, 9.4.3, 
and 10.5) 
2) Added information to 
amendment history in Section 
10.4 
3) Specified “language barrier” 
as exclusion criteria in Section 
5.2 
4) Minor formatting corrections 
1) To reflect changes made 
during ClinicalTrials.gov 
review 
2) To meet GCP requirements 
3) All health coaching and health 
education are available in 
English only 

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V1.2 
05/20/2020 
1) Included new section 
“TELEMEDICINE 
PROCEDURES/PROCESSES 
AS DEEMED NECESSARY 
DUE TO COVID-19” 
2) Modified table in 1.3 Schedule 
of Activities (SOA) to expand 
timeframe of T0 
measurements 
3) Updated inclusion criteria for 
Systolic BP from “>140” to 
“≥140” 
4) Updated inclusion criteria for 
EgfR lookback period from 12 
months to 18 months  
5) Specified “pregnant” 
exclusion criteria 
6) Specified that Dr. Resnicow is 
leading training (see Section 
6.4) 
7) Clarified information provided 
on DSMB’s roster (see 
Sections 8.2 & 10.1.6) 
8) Minor formatting/text 
corrections 
1) Remote procedures now 
included to adhere to COVID-
19 related restrictions on in-
person study activities 
2) To accommodate time needed 
for remote procedures 
3) Systolic BP criterion was 
intended to be “greater than or 
equal to 140” 
4) Patient’s annual return visits 
may be scheduled more than 
12 months out from their last 
EgfR test 
5) Being pregnant is an exclusion 
criterion, whether a patient 
self-identifies as pregnant or if 
their medical record indicates 
pregnancy. 
6) Dr. Fagerlin is now at the 
University of Utah and unable 
to co-lead training sessions 
with Dr. Resnicow 
7) The study biostatistician may 
attend the DSMB’s meetings, 
but will not be a DSMB 
member 
 
V1.3 
10/15/2020 
1) Specified “Patient Numeracy 
(SNS)” in Appendix 1: 
Outcome Measures 
2) Removed reference of Section 
8.3.5 from Section 10.1.10. 
3) Added S-TOHFLA as method 
of measuring Health Literacy in 
Appendix 1: Outcome 
Measures 
4) Add “Schedule of Activities” 
information to Section 11. 
 
1) To clarify the instrument used 
for this variable (SNS) 
2) Section 8.3.5 describes AE 
reporting, not deviations  
3) The REALM-SF measure can 
only be used during in-person 
study visits. Due to the need to 
measure health literacy 
remotely, the S-TOHFLA has 
been added to the T0 survey. 
4) Expands upon protocol’s 
flexibility regarding visit 
tolerance windows due to newly 
adapted remote processes. 
V1.4 
02/03/2022 
1) Increase target enrollment 
number 
2) Allow more contacts/in-person 
contacts 
3) Allow using EMR lab results 
for missing labs 
 
 
1) In order to achieve the same 
overall power for statistical 
analysis. 
2) To extend protocol’s flexibility 
regarding contact numbers and 
methods to retain participants 

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3) Using EMR lab results can 
supplement missing labs data 
affected by Covid-19 pandemic  
 
V1.5 
8/18/2022 
1) Change the blood pressure 
eligibility criteria 
2) Add some conditions to 
“Expected” list of adverse 
events 
1) Per recommendation from 
the Data and Safety 
Monitoring Board (DSMB) 
of the study, we will lower 
the blood pressure 
eligibility criteria from 
140/90 to 130/80 in order to 
include more potential 
patients and to be 
consistent with the more 
recent blood pressure 
targets in guidelines. 
2) We have found some 
adverse events that should 
be added to the “expected” 
adverse events list 
 
V1.6 
2/2/2023 
1) Modify “An investigator 
may discontinue or 
withdraw a participant 
from the study for the 
following reasons” to 
include “If the 
participant changes their 
primary care provider to 
be outside of the health 
system” 
1) All patient participants’ 
PCPs are involved in the 
study, and we communicate 
with them throughout the 
study. This includes 
sharing recordings of 
intervention participants’ 
health coach calls and 
notifying the PCP if lab 
values or blood pressure 
readings are outside of the 
“normal” range. If a 
participant gets a PCP 
outside of the study’s 
health systems, we cannot 
communicate with them to 
share this information. 
V 1.7 
3/20/2023 
1) Provide references to survey 
answers to participants who 
request it, but only at the end of 
their participation 
2) Clarify that on-site follow up 
may occur at any scheduled 
appointment within the health 
system 
3) Clarify that blood pressure 
readings can be collected from 
the EMR 
1) The visit survey contains some 
questions with right and wrong 
answers. On occasion, participants 
request the correct answers. While 
it is not our intention to send out 
mass communications, we will 
provide references to where they 
can get answers to some of the 
surveys as appropriate. 
2) Section 11 states “study team will 
also try to make in-person contacts 
with participants prior to or after 
their other on-site medical 
appointments.” We have added the 
text in section 8.1 to mirror this 
and explain we may approach 
participants at scheduled 
appointments within the health 

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system. In clinic, researchers will 
find a quiet, private area to talk to 
the participants. 
3) Adding this to match the text in 
section 9.2 stating “Additional 
clinical BPs in the EMR will be 
recorded as available.” 
V 1.8 
5/13/2024 
1) Introduce primary care providers 
as a subgroup of the study 
population (Aim 3) 
2) Update information on the PI and 
Co-Is 
3) Clarify that EMRs/medical 
records include those used by 
specialties within the health 
system 
1) Aim 3 of the study will assess the 
adoption, fidelity, and perceived 
usefulness of the intervention 
among primary care providers 
once their patients have completed 
Aim 2. Additional details on 
measurement methods and consent 
procedures have been included. 
2) Updates the PI’s change in 
academic rank and contact 
information and removes Co-Is 
who are no longer part of the study 
team. 
3) Clarifies that we will collect data 
(lab results, blood pressure 
readings, and AEs) from all 
electronic medical records (EMRs) 
within the health system, including 
those used by various specialties. 
V 1.9 
3/17/2025 
1) Specify health coach perceptions 
of the intervention in the 
implementation outcome 
assessment 
2) Describe the consent procedure 
for health coach survey 
3) Update endpoints to include 
updated secondary 
endpoints/outcomes 
4) Revise the schema to reflect 
updates to enrollment and study 
visit processes implemented 
since COVID-19 
5) Add a footnote noting the larger 
tolerance windows for study 
visits 
6) Update Appendix 1: Outcome 
Measures 
1) Add details on assessing health 
coach perceptions of the 
intervention as an exploratory 
outcome via an open-ended 
survey 
2) Outlines procedures for obtaining 
informed consent from health 
coaches prior to survey 
participation 
3) Clarify protocol language to align 
with the outcome measures listed 
on ClinicalTrials.gov 
4) Clarify that enrollment occurred 
by phone; study visit data 
(surveys and blood pressure) are 
collected via phone, email, mail, 
or in person, and biospecimens 
are collected at the clinic lab at 
patients’ convenience 
5) Clarify that data-collection 
tolerance windows have been 
extended from 7-14 days to a few 
months 
6) Update secondary outcomes, 
reclassify EMR-based medication 
adherence as an exploratory 
outcome, and revise time points 
for the provider survey and coach 
perception assessment 
 

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10.5 APPENDICES 
APPENDIX 1: OUTCOME MEASURES 
Variable 
Time point(s) 
Variable type 
Outcome type 
Demographics/patient characteristics (age, sex, gender, race, ethnicity, education, 
income, general health status) 
t(0) 
continuous, 
categorical 
N/A 
Co-morbid conditions (cardiovascular dz, liver dz, diabetes, CHF, cerebrovascular dz) 
t(0) 
categorical 
N/A 
Health Literacy (REALM-SF/S-TOHFLA) 
t(0) 
continuous 
N/A 
Medications of interest (BP, diuretics, and statins) 
t(0) 
categorical 
N/A 
Patient Numeracy (SNS) 
t(0) 
continuous 
N/A 
Change in systolic BP between baseline and 12 months 
t(0), t(3) 
continuous 
primary 
Change in diastolic BP between baseline and 12 months 
t(0), t(3) 
continuous 
secondary 
Change in EMR-recorded BP between baseline and 12 months 
t(0), t(3) 
continuous 
secondary 
Change in study visit BP supplemented with EMR BP if missing 
t(0), t(3) 
continuous 
secondary 
Change in BP using the combined dataset using all study visit and EMR BP values 
t(0), t(3) 
continuous 
secondary 
Slope of systolic BP between baseline and 12 months using all available BP values 
t(0), t(1), t(2), t(3) 
continuous 
secondary 
Slope of diastolic BP between baseline and 12 months using all available BP values 
t(0), t(1), t(2), t(3) 
continuous 
secondary 
BMI (weight in kg/height in meters squared) 
t(0), t(1), t(2), t(3) 
continuous 
N/A 
Estimated Glomerular Filtration Rate (EgfR) 
t(0), t(3) 
continuous 
secondary 
Serum creatinine  
t(0), t(3) 
continuous 
secondary 
Urine protein-creatinine ratio 
t(0), t(3) 
continuous 
secondary 
Medication adherence (MMAS-8) 
t(0), t(1), t(2), t(3) 
continuous 
secondary 
Medication adherence from electronic medical record 
t(0), t(1), t(2), t(3) 
continuous 
exploratory 
CKD knowledge (KiKS) 
t(0), t(1), t(2), t(3) 
continuous 
secondary 
Self-efficacy for med adherence (MASES-R) 
t(0), t(1), t(2), t(3) 
continuous 
secondary 
Self-efficacy for disease self-management (PKDSMS) 
t(0), t(1), t(2), t(3) 
continuous 
secondary 
Patient motivation (TSRQ) 
t(0), t(1), t(2), t(3) 
continuous 
secondary 
Satisfaction with CKD care (CAT) 
t(0), t(1), t(2), t(3) 
continuous 
secondary 
Satisfaction with CKD care (CCM) 
t(0), t(1), t(2), t(3) 
continuous 
secondary 
Self-report BP-related behaviors (sodium, activity) 
t(0), t(1), t(2), t(3) 
continuous 
secondary 
Patient plans to revisit EDI 
t(0) 
categorical 
exploratory 

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Variable 
Time point(s) 
Variable type 
Outcome type 
Patient portal use 
t(0), t(1), t(2), t(3) 
categorical 
exploratory 
Patient review of coaching educational materials 
t(1), t(2), t(3) 
categorical 
exploratory 
Provider discipline 
t(0) 
categorical 
N/A 
Provider years in practice 
t(0) 
continuous  
N/A 
Provider gender 
t(0) 
categorical 
N/A 
Provider race 
t(0) 
categorical 
N/A 
Provider adoption based on EMR query and patient survey 
t(0) 
categorical 
secondary 
Perception of usefulness by provider survey 
after all patient 
follow-ups, up to 
one year 
continuous, 
categorical 
secondary 
Provider fidelity measured by EMR query 
t(0) 
categorical 
secondary 
Provider practice size (number of patients yearly) 
t(0) 
continuous  
N/A 
Provider affiliated health system 
t(0) 
categorical 
N/A 
Clinic ‘'Discipline’' 
t(0) 
categorical 
N/A 
Geographic location (patient home and clinic 5-digit zip codes) and income data 
t(0) 
categorical 
N/A 
Clinic characteristics  
t(0) 
categorical 
N/A 
Visit time with provider 
t(0) 
continuous  
secondary 
Total time in clinic 
t(0) 
continuous  
secondary 
Coach perceptions of coach intervention 
after all patient 
follow-ups, up to 
one year 
categorical 
 
exploratory 
Number of calls, number completed on time, length of time, coach content of calls 
across study 
duration 
continuous 
N/A 
Coach call survey - online questions coach asks at follow up calls 
across study 
duration 
categorical 
exploratory 
Coach baseline survey - patient values report cared, grades of behaviors 
t(0) 
categorical 
exploratory 
Goal reminder questions 
across study 
duration 
categorical 
exploratory 
Patient perceptions of health coaching  
t(3) 
continuous 
secondary 
Cost and efficiency of coaching related to intervention 
t(3) 
continuous 
exploratory 

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11 TELEMEDICINE PROCEDURES AS DEEMED NECESSARY DUE TO COVID-19 
Due to the COVID-19 pandemic, the CHECK-D study is adding the following remote procedures and 
policies in order to adhere to any restrictions put in place throughout the intervention period of the 
study. Recruitment, enrollment, study visits, and data collection will occur in-person only when deemed 
safe for participants and staff. These changes apply to all participants and will remain in effect post-
pandemic. 
Telehealth PCP Appointments now eligible for screening and recruitment: All patients scheduled for 
telehealth appointments (such as, phone visits, video visits) with their PCPs at participating clinics will be 
screened for eligibility, and their healthcare providers will be prompted to review the EDI with eligible 
patients. After patients check out, a study team member will approach patients over the phone for 
recruitment. 
Screening and Recruiting Patients Not Scheduled for Upcoming Appointments: In the event that 
recruitment is slowed due to any of the participating clinics ceasing or significantly reducing the amount 
of in-person and telehealth appointments on their schedules, the study team will screen these clinics for 
eligible patients that may or may not have an upcoming appointment with their healthcare provider. 
The study team will make every effort to work with the healthcare providers for recruitment and review 
of the EDI, as originally intended. The study team will send patients an introductory letter before 
approaching them over the phone for recruitment. 
Electronic Consent: Consent can now be obtained using HIPAA complaint, cloud-based electronic 
signature technology (e.g., SignNow), where an electronic signature is obtained on a digital version of 
the informed consent. If the patient is consented electronically, they will be given a copy of the consent 
form (hard copy) for their personal records. Consent can still be obtained in-person and over the phone. 
Surveys: All enrolled participants will be able to complete surveys remotely. Participants will be able to 
complete a paper survey to mail back to the study team, or receive an electronic version of the survey 
via email distribution.  
At Home Blood Pressure Monitors: Each participant will receive an at-home blood pressure monitor 
from the study team. These monitors will be used by participants to check blood pressure after 
enrollment and at 1, 6, and 12 months after enrollment. Whenever it is possible, in-person BP readings 
will also be taken by research staff. Blood pressure readings from the medical records, including those 
used by specialties within the health system, may also be collected when readings are within the study-
determined visit windows. 
Blood/Urine Tests: Lab orders will continue to be placed by the study team after the enrollment visit 
and 12 months after enrollment. Lab completion will be done as close to study time-points as stay-at-
home orders and patient availability allows. However, if labs are not complete but there are equivalent 
test results available in the medical records, including those used by specialties within the health 
system, we will collect data using the existing results. This will apply to both Intervention and Control 
groups. 

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EDI Distribution: The study team will work with each participating clinic to make sure that enrolled 
participants receive the EDI. 
Schedule of Activities: During the new and unprecedented times brought on by the COVID-19 
pandemic, the CHECK-D study team has made great strides to adapt and add processes aligned with 
restrictions in research activities and contact with participants. The tremendous changes required 
demands flexibility as we interact with participants and collect data.  We will continue to collect all data 
for patient study visits (t0-t3) with every effort to align with the “schedule of activities” in our original 
IRB protocols. However, because of patient activity that is now virtual, may rely on mail and 
acknowledges participant needs for flexibility, the collection dates for study measures may fall outside 
of the original “schedule of activities” visit tolerance windows. Thus from this point forward, data 
collection events that fall outside of the visit tolerance windows will not be considered protocol 
deviations and not be reported as such. Exact time points of data collection will be documented in study 
logs, and accounted for in our analytic plan. 
Number of Contacts: Before a participant is deemed lost to follow-up, the investigator or designee will 
make every effort to regain contact with the participant (where possible, no less than 3 contact 
attempts). The contacts may include telephone calls, emails, in-person* contacts and a lost to follow up 
reminder letter to the participant’s last known mailing address or local equivalent methods.  
*Sometimes patients come back to clinic for follow-ups. We have found that in person contact may be a 
better or the only way to follow up with patients with limited resources (e.g., due to no internet, 
inconsistent phones). In order to reduce the rate of lost-to follow-up, the study team will also try to 
make in-person contacts with participants prior to or after their other on-site medical appointments if 
we cannot reach them by phone or email.  
 
 

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13 PROTOCOL SIGNATURE PAGE 
 
Protocol Title: Controlling Hypertension through Education and Coaching in Kidney Disease (CHECK-D) 
 
 
Protocol Number: Version 1.9 
 
 
Protocol Version/ Date: _________________________________________________________________ 
 
 
Sponsor Name: Health and Human Services, National Institutes of Health, National Institute of Diabetes 
and Digestive and Kidney Diseases 
 
 
 
Declaration of Investigator 
 
I confirm that I have read the above-mentioned protocol and its attachments. I agree to conduct the 
described trial in compliance with all stipulations of the protocol, regulations and ICH E6 Guideline for 
Good Clinical Practice (GCP). 
 
  
 
Principal Investigator Name:  _____________________________________________________________ 
 
 
 
Principal Investigator Signature:  __________________________________________________________ 
 
                                                            
 
Date:  ________________________________________________________________________________