Clinical trial NCT03459807
Conditions: Blood Pressure End Stage Renal Disease on Dialysis (Diagnosis) Chronic Kidney Diseases Chronic Kidney Disease Stage 5
Keywords: Blood pressure Hemodialysis End-stage-renal-disease Chronic kidney disease
Sponsor: University of California, San Francisco
Start date: 2018-03-23; Completion date: 2018-12-06
Enrollment: 50 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Blood pressure may be one of the most important modifiable risk factors for cardiovascular disease in patients with end-stage-renal-disease undergoing maintenance hemodialysis. Although a systolic blood pressure \<140 mmHg treatment target has been recommended, there remains uncertainty on which blood pressure should be targeted, more specifically that measured in the dialysis unit or at home. Observational studies have reported a paradoxical U-shaped associated with dialysis unit (pre-dialysis) systolic blood pressure and cardiovascular events and death (where blood pressure below 140 mmHg is actually linked with poor outcomes). Conversely, the same studies have reported a linear association between higher home systolic blood pressure and worse clinical outcomes, where blood pressure below 140 mmHg is associated with better outcomes. This pilot clinical trial aims to address this important question.

Detailed description:
Blood Pressure Lowering in Dialysis (BOLD) is a pilot randomized controlled trial of 50 maintenance hemodialysis patients in San Francisco and Seattle to test whether targeting a home systolic blood pressure \<140 mmHg (versus a pre-dialysis systolic blood pressure \<140 mmHg) is feasible and safe. The study duration is 4 months and blood pressure targets will be achieved through dry weight adjustment and adjustment of standard anti-hypertensive therapies by the study team. The primary outcomes are focused on feasibility and safety. The home blood pressure treatment arm will also have the opportunity to utilize a blood pressure monitor with Bluetooth capabilities. The rates of utilization of mobile health technology in this population will also be assessed as an outcome. This pilot trial will provide key data to design a larger trial focused on clinical outcomes.

Arms: arm 1: Participants will be asked to take morning and evening blood pressures every two weeks on a non-dialysis day.

Participants will be asked to transmit these measures to the study team at minimum every 2 weeks either via Bluetooth technology, a manual log, telephone call, text message, e-mail, or verbal communication.

Assigned intervention will be dry weight adjustment and/or adjustment of standard anti-hypertensive medications. arm 2: Blood pressures taken in the clinical setting at prior to start of dialysis treatment will be recorded.

Assigned intervention will be dry weight adjustment and/or adjustment of standard anti-hypertensive medications.
Interventions: intervention 1: Anti-Hypertensive medications intervention 2: Dry Weight Adjustment
Intervention descriptions: intervention 1: Use of standard Anti-Hypertensive medications intervention 2: The participant's target post-dialysis dry weight is adjusted

Protocol documents:
Prot_SAP_001.pdf: 
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THE BLOOD PRESSURE LOWERING IN DIALYSIS TRIAL 
 (THE BOLD TRIAL) 
 
 
 
 
Sponsored by: 
 
Chi-yuan Hsu, MD, MSc and Nisha Bansal, MD, MAS 
 
 
 
Investigators 
Chi-yuan Hsu, MD, MSc 
Division of Nephrology 
University of California 
San Francisco, CA USA 
 
Nisha Bansal, MD, MAS 
Division of Nephrology 
University of Washington 
Seattle, WA USA 
 
 
 
Funding Organizations: 
National Institutes of Health, Satellite Healthcare 
 
 
Investigational Product: None 
IND Number: Not applicable 
 
 
 
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PROTOCOL AGREEMENT 
 
In my formal capacity as investigator, my duties include ensuring the safety of the study 
subjects enrolled under my supervision.  It is understood that all information pertaining to 
the study will be held strictly confidential and that this confidentiality requirement applies 
to all study staff at this site. Furthermore, on behalf of the study staff and myself, I agree 
to maintain the procedures required to carry out the study in accordance with accepted 
GCP principles and to abide by the terms of this protocol. 
 
Protocol Number:  1.1 
 
Protocol Title:  The BOLD Trial: Blood Pressure Lowering in Dialysis Trial 
 
Protocol Date:  February 5, 2018 
 
 
 
 
Investigator Signature  
 
Date 
 
Print Name and Title 
Site # 
 
 
Site Name 
 
Address 
 
 
 
 
 
 
 
Phone Number 
 


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TABLE OF CONTENTS 
 
1 
INTRODUCTION............................................................................................................... 8 
      1.1 
Background ................................................................................................................. 8 
2 
STUDY RATIONALE ........................................................................................................ 8 
2.1 
Risk / Benefit Assessment ........................................................................................... 10 
3 
STUDY OBJECTIVES ....................................................................................................... 11 
3.1 
Primary Objectives ...................................................................................................... 11 
4 
STUDY DESIGN ................................................................................................................. 11 
4.1 
Study Overview ........................................................................................................... 11 
5 
CRITERIA FOR EVALUATION ..................................................................................... 12 
5.1 
Primary Outcomes ....................................................................................................... 12 
      5.2    Secondary Outcomes 
 
 
 
 
 
 
      12 
6 
SUBJECT SELECTION .................................................................................................... 13 
6.1 
Study Population ......................................................................................................... 13 
6.2 
Inclusion Criteria ......................................................................................................... 13 
6.3 
Exclusion Criteria ....................................................................................................... 13 
6.4 
Strategies for Recruitment and Retention ................................................................... 13 
7 
STUDY TREATMENTS .................................................................................................... 13 
7.1 
Method of Assigning Subjects to Treatment Groups .................................................. 14 
7.2 
Blinding   …………………………………………………………………………....14  
7.3 
Measuring Home SBP ................................................................................................. 14 
7.4 
Measurement of In-Center Pre-Dialysis SBP .............................................................. 15 
7.5 
Treatment Adherence .................................................................................................. 15 
7.6 
Temporary Discontinuation ........................................................................................ 15 
7.7 
Lost to Follow-Up ....................................................................................................... 15 
8 
STUDY PROCEDURES AND GUIDELINES ................................................................. 16 
8.1     Approach to Blood Pressure Management .................................................................. 16 
8.2 
Clinical Assessments ................................................................................................... 17 
8.2.1    Demographics ..................................................................................................... 17 
8.2.2    Medical History and Concomitant Medications ................................................. 17 
8.2.3    Blood Pressure: Assessment of episodes and symptoms of intra-dialytic   
hypotension .................................................................................................................... 17 
8.2.4    Adverse Events ................................................................................................... 17 
8.3 
Clinical Laboratory Measurements ............................................................................. 18 
9 
EVALUATIONS BY VISIT ............................................................................................... 18 
      9.1    Visit 0: screening visit 
      9.2    Visit 1: baseline visit 
9.3 
Visits 2-8 1 
9.4 
Visit 9 (final study visit)  


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10 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION ........................ 19 
10.1 Adverse Events ........................................................................................................... 19 
10.2 Serious Adverse Experiences (SAE) ........................................................................... 20 
10.2.1    Serious Adverse Experience Reporting ............................................................ 21 
10.2.2    Post-study Adverse Event................................................................................. 21 
11 DISCONTINUATION AND REPLACEMENT OF SUBJECTS................................... 21 
11.1 Early Discontinuation of Study InterventionI ............................................................. 21 
11.2 Replacement of Subjects ............................................................................................. 22 
12 PROTOCOL VIOLATIONS ............................................................................................. 23 
13 DATA SAFETY MONITORING ...................................................................................... 24 
14 STATISTICAL METHODS AND CONSIDERATIONS ............................................... 24 
14.1 Data Sets Analyzed ..................................................................................................... 23 
14.2 Demographic and Baseline Characteristics ................................................................. 23 
14.3 Analysis of Primary Endpoint ..................................................................................... 23 
14.4 Analysis of Secondary Endpoints ............................................................................... 23 
14.5 Sample Size and Randomization ................................................................................. 23 
15 DATA COLLECTION, RETENTION AND MONITORING ....................................... 25 
15.1 Data Collection Instruments ........................................................................................ 25 
15.2 Data Management Procedures ..................................................................................... 25 
15.3 Data Quality Control and Reporting ........................................................................... 24 
15.4 Archival of Data .......................................................................................................... 24 
15.5 Availability and Retention of Investigational Records ............................................... 24 
15.6 Monitoring .................................................................................................................. 25 
15.7 Subject Confidentiality................................................................................................ 25 
16 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS .................. 25 
16.1 Protocol Amendments ................................................................................................. 25 
16.2 Institutional Review Boards and Independent Ethics Committees ............................. 25 
16.3 Informed Consent Form .............................................................................................. 26 
16.4 Publications ................................................................................................................. 26 
16.5 Investigator Responsibilities ....................................................................................... 27 
 


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LIST OF ABBREVIATIONS 
Add all other abbreviations referenced in the protocol and delete any not referenced in 
the protocol. 
AE 
adverse event 
BUN 
blood urea nitrogen 
CFR 
Code of Federal Regulations 
CRF 
case report form 
DMC 
Data Monitoring Committee 
DSMB 
Data Safety Monitoring Board 
ESRD 
FDA 
End stage renal disease 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HD 
HIPAA 
Hemodialysis 
Health Insurance Portability and Accountability Act of 1996 
ICF 
informed consent form 
IDH 
intra-dialytic hypotension  
IRB 
Institutional Review Board 
IV 
intravenous 
mEq 
milliequivalent 
PI 
Principal Investigator 
PHI 
RAAS 
SAE 
Protected Health Information 
renin-angiotensin-aldosterone system 
serious adverse experience 
SBP 
 
 
systolic blood pressure 
 
  


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PROTOCOL SYNOPSIS 
TITLE 
The BOLD Trial: Blood Pressure Lowering in Dialysis Trial 
PIs 
Chi-yuan Hsu, MD, MSc 
Nisha Bansal, MD, MAS 
FUNDING 
ORGANIZATION 
NIH-NIDDK and Satellite Healthcare 
NUMBER OF SITES 
2 
RATIONALE 
Treating home blood pressure may be better than treating dialysis unit 
blood pressure to improve outcomes in patients on maintenance 
hemodialysis  
STUDY DESIGN 
Randomized controlled trial 
PRIMARY 
OBJECTIVE 
 To determine the feasibility of and adherence to a strategy of dry 
weight adjustment and anti-hypertensive medication titration to 
achieve home systolic blood pressure <140 mmHg vs. a pre-
dialysis systolic blood pressure <140 mmHg over 4 months. 
 To test the safety and tolerability of an intervention to achieve 
home systolic blood pressure <140 mmHg. 
SECONDARY 
OBJECTIVES 
 To determine acceptability of a Bluetooth-enable home blood 
pressure monitor in dialysis patients 
 To determine whether the strategy of targeting home systolic 
blood pressure versus in-center pre-dialysis systolic blood 
pressure leads to differences in blood pressure levels  
NUMBER OF 
SUBJECTS 
50 (or 25 in each of the two arms) 
SUBJECT 
SELECTION 
CRITERIA 
Inclusion Criteria: 
1. Provision of signed and dated informed consent form 
2. Undergoing in-center, thrice weekly hemodialysis for treatment of 
end stage renal disease 
3. Greater than 3 months since initiation of dialysis 
4. Aged 18 years or above  
5. Able to obtain a brachial blood pressure at dialysis and at home 
Exclusion Criteria: 
1. Pregnancy, anticipated pregnancy, or breastfeeding as this will  
require increase to more than three time a week dialysis and/or 
preclude use of some classes of blood pressure medications 
2.  Incarceration or institutionalized living which may prohibit 
measurement of home blood pressure 
3. Participation in another intervention study that may affect blood 


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pressure 
4. Patients in whom systolic blood pressure is not measurable (e.g. 
those with left ventricular assist devices) 
5. Hypotension: average pre-dialysis systolic blood pressure <100 
mmHg over last 2 weeks prior to screening while not taking any blood 
pressure medications 
6. Life expectancy <4 months 
7. Anticipated living donor kidney transplant within 4 months 
INTERVENTION 
 Dry weight and anti-hypertensive medication adjustment to target 
home systolic blood pressure vs. in-center pre-dialysis systolic 
blood pressure <140 mmHg 
DURATION OF 
SUBJECT 
PARTICIPATION 
AND DURATION OF 
STUDY 
The total duration of the study is expected to be 24 months 
PRIMARY ENDPOINT 
 
Feasibility of intervention 
 
Adherence to intervention 
 
Safety 
 
Tolerability 
SECONDARY 
ENDPOINTS 
 
Of the home BP participants, we will determine the modality 
they choose to transmit their home BP readings 
 
Differences in blood pressures between treatment groups as 
assessed by blood pressure at dialysis and 44-hour intra-dialytic 
ambulatory blood pressure 
STATISTICS 
Primary Analysis Plan 
 We will quantify the screen: enroll ratio 
 We will report the proportion of participants in the home BP arm 
that complete the training, percent of home BP readings 
completed over the study period, and mean time from home BP 
measurement to transmission to the study team. 
 We will quantify rates of completion and drop out in each 
treatment arm. 
 We will report rates of hypotension and hypertension in each 
treatment arm. 
 We will quantify rate of intra-dialytic hypotension and symptoms 
related to intra-dialytic hypotension in each treatment arm.  
Rationale for Number 
of Subjects 
This pilot study is designed to test study logistics and optimize study 
interventions within the confines of a pilot study budget, not to find 
statistically significant differences between the two arms.   


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1 
INTRODUCTION 
1.1 
Background  
Blood pressure (BP) is a powerful and modifiable risk factor for cardiovascular (CVD) 
events and death in the general population.1-4 Observational studies document a 
progressive increase in risk of BP-related end-organ damage as systolic BP (SBP) rises 
above 115 mmHg.1-4 Lowering of SBP to less than 140 mmHg had been the conventional 
target for treatment of hypertension.5 Recent data from the SPRINT trial showed that 
targeting even lower SBP targets (<120 mmHg) lowered rates of CVD events and death in 
an at-risk population with or without moderate maintenance kidney disease.6  
End-stage renal disease (ESRD) patients on maintenance maintenance hemodialysis (HD) 
have high rates of CVD events and death.7-9 Approximately 2 million ESRD patients 
worldwide are treated with HD.10 Reported CVD mortality rates are 10 to 30 times higher 
in HD patients compared with the general population.7 Hypertension is present in >90% of 
patients at the initiation of HD10 and persists over time in more than two-thirds.10 
Improved management of BP in this high risk population could potentially yield 
substantial benefits. 
Management of BP in HD patients is in dire need for better evidence to guide 
management. The management of BP in HD patients has long presented a conundrum for 
physicians.11-14 Differing from the general population, observational studies have 
repeatedly shown that HD patients with SBP measured prior to the dialysis treatment (pre-
dialysis SBP; also referred to as dialysis-unit SBP) of <140 mmHg experience higher risk 
of mortality than those with SBP >140 mmHg (U-shaped association).11-24 And patients 
with pre-dialysis SBP of 150-179 mmHg appear to be at similar, if not lower, risk for 
death compared to those with pre-dialysis SBP of 140-149 mmHg, even accounting for 
differences in patient characteristics. Nevertheless, practice guidelines have continued to 
promote treating pre-dialysis SBP.25-29 For example, a pre-dialysis BP goal of <140/90 
mmHg is recommended by Kidney Disease Outcomes Quality Initiative (KDOQI), despite 
the acknowledgement “it is unclear which blood pressure reading should be used as the 
guide for therapy.”30  
2 
STUDY RATIONALE 


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Figure 1. Association of pre-dialysis SBP (left panel) and out-of-dialysis-unit SBP (right panel) 
and risk of all-cause mortality (Bansal…Hsu, Hypertension 2015) 
We propose that solving this conundrum requires physicians to measure and treat out-of-
dialysis-unit SBP rather than dialysis-unit SBP. We base our hypothesis on newly 
generated observational data from a NIH-sponsored multi-center cohort of incident HD 
patients (the Maintenance Renal Insufficiency Cohort [CRIC] study). We confirmed a 
“paradoxical” U-shaped association between dialysis-unit SBP and risk of all-cause 
mortality (Figure 1 left panel), but also showed a linear stepwise association between 
SBP measured outside of the dialysis-unit and risk of mortality (Figure 1 right panel), in 
a pattern similar to that in the general population.24  
 
Our data are consistent with prior single-center studies.15,31-33 We have since investigated 
adjudicated cardiovascular (CVD) events, which is novel as all-cause death is more 
commonly available as an outcome in dialysis epidemiology studies. Similar to all-cause 
mortality, there was a U-shaped association between dialysis-unit SBP and risk of CVD 
events (defined as a composite of heart failure, myocardial infarction, ischemic stroke, and 
peripheral artery disease events)(Figure 2 left panel). In contrast, there was a linear 
stepwise association between out-of-dialysis-unit SBP with risk of CVD events (Figure 2 
right panel).34  


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Table 1. Cross-tabulation 
of dialysis-unit vs. out-of-
dialysis-unit SBP in the 
CRIC study (N=377) 
(Bansal…Hsu, 
Hypertension 2017)  
Figure 2. Association of pre-dialysis SBP (left panel) and out-of-dialysis-unit SBP (right panel) 
and risk of cardiovascular events (Bansal…Hsu, Hypertension 2017)
 
Since these associations were observed in the same patients, they refute prior hypotheses 
that the reason for the U-shaped association between dialysis unit SBP and adverse 
outcomes is due to inclusion of “sicker” patients (such as those with severe systolic heart 
failure)35,36 or due to physiological state unique to HD patients.11,37 Instead, we 
hypothesize the inability to mount an elevated BP in response to fluid accumulated 
between HD sessions—reflected in the dialysis-unit BP documented at the start of each 
HD session—is an adverse prognostic marker. In short, dialysis-unit BP may reflect 
mostly the transient effect of inter-dialytic volume expansion, rather than being a good 
overall indication of BP load as it relates to end-organ damage. Alternatively, perhaps 
some type of “white-coat hypertension/effect” particular to HD patient is operative here. 
But regardless of the exact pathophysiologic mechanism, these data strongly suggest that 
the focus should be on measuring and treating out-of-dialysis-unit BP, rather than 
dialysis-unit BP, which will be a significant change from current practice.  
In our recent study, dialysis-unit SBP was generally higher than out-of-dialysis-unit SBP 
and the correlation was weak between the two measures (p=0.34). Nearly two-thirds 
(166/269=62%) of patients in this study with dialysis unit SBP >140 mmHg had out-of-
dialysis-unit SBP <140 mmHg (Table 1). Thus, targeting 
dialysis-unit SBP may be leading to BP overtreatment in a 
substantial number of dialysis patients (those with high 
dialysis-unit but low out-of-dialysis-unit SBP), which may 
cause intra-dialytic hypotension, myocardial stunning and 
adverse cardiac remodeling.38-40 Concurrently, other patients 
may be undertreated (those with low dialysis-unit SBP but 
high out-of-dialysis-unit SBP), which may result in end-organ damage.  
2.1 
Risk / Benefit Assessment 
This trial proposes to target an out-of-dialysis-unit SBP <140 mmHg vs. dialysis-unit SBP 
<140 mmHg among maintenance HD patients by adjusted estimated dry weight and anti-
hypertensive medications. The algorithm will adjust RAAS inhibitors, beta-blockers, 
calcium channel blockers and other anti-hypertensive medications. The doses that will be 
prescribed will be within the scope of FDA approved doses. Potential risks of the study 
medications include: hypotension and bradycardia and associated symptoms such as 
dizziness. Subjects will be monitored for these potential risks closely through direct 
contact with the study coordinators. There is also a small potential risk of loss of 
confidentiality.  


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Blood pressure is one of the most important risk factors for cardiovascular disease and 
death in the general population. HD patients are at greatly increased risk of cardiovascular 
disease and death. So optimizing BP control in HD patients could potential yield 
substantial benefit. The proposed study is a pilot clinical trial test to test the feasibility and 
safety of treating dialysis-unit versus out-of-dialysis-unit blood pressure in dialysis 
patients. This will be most useful to practicing physicians, patients and public health 
planners.  
 
Since the value of the findings is potentially large, we believe the proposed study’s 
benefits outweigh the risks. 
3 
    STUDY OBJECTIVES 
3.1 
Primary Objectives 
             The primary objectives of the BOLD Trial are: 
                To determine the feasibility of and adherence to a strategy of dry weight 
adjustment and anti-hypertensive medication titration to achieve home systolic 
blood pressure <140 mmHg vs. a pre-dialysis systolic blood pressure <140 
mmHg over 4 months. 
                To test the safety and tolerability of an intervention to achieve home 
systolic blood pressure <140 mmHg. 
4 
STUDY DESIGN 
       4.1        Study Overview 
This is a two center, placebo-controlled, randomized 4 month trial of 50 subjects.  This 
will be a pilot clinical trial to test the feasibility, adherence, safety and tolerability of a 
strategy of targeting home SBP <140 mmHg vs. dialysis-unit (pre-dialysis) SBP <140 
mmHg. These targets will be achieved using an algorithm of estimated dry weight and 
anti-hypertensive medication adjustment. Home BP measures will be recorded every 
other week and transmitted to the study team. We have chosen the same SBP target and 
the same algorithm for both arms so we can test the effect of the setting of BP 
measurement (rather than a specific BP target or medication).  Participants will have 
contact with the study team every 2 weeks to obtain information on interim study 
outcomes (updated medical history, completion of study questionnaires) and adjust 
estimated dry weight and anti-hypertensive medications. A final study visit will occur at 
4 months. 
 


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5 
CRITERIA FOR EVALUATION 
   5.1      Primary Outcomes 
Feasibility 
 The study will determine how many eligible participants (and their nephrologists) 
agree to participate in the study (screen: enroll ratio)  
Adherence 
 We will determine what proportion of participants in the home BP arm successfully 
complete home BP training, perform home BP readings every other week and 
transmit data in a timely manner to the study team via any method.  
 We will determine the drop out and completion rate in each arm.  
 
Safety 
 
We will monitor for excessively low blood pressure readings (e.g. dialysis unit blood 
pressure readings of <90 mmHg) and dangerous consequences of excessively low 
blood pressure (e.g. syncope, falls). 
 
We will monitor for excessively high blood pressure readings (e.g. dialysis unit blood 
pressure readings of >200 mmHg) and dangerous consequences of excessively high 
blood pressure (e.g. flash pulmonary edema).     
 
Tolerability 
 We will review the dialysis record every 2 weeks to determine frequency of 
intra-dialytic hypotension, defined as SBP<90 mmHg during dialysis 
 For symptoms assessment, we will contact participants (in both treatment 
groups) once every 2 weeks. Patients will be queried via interview (either phone 
or during dialysis) about adverse events noted during the immediate past HD 
session which will include symptoms of hypotension92 such as cramping 
(yes/no), dizziness/lightheadedness (yes/no) and fatigue (yes/no).92-94 We will 


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also ask patients “how long did it take you to recover from your last dialysis 
treatment.” 
 
5.2 Secondary Outcomes 
 Acceptability of a Bluetooth-enabled home BP monitor: of the home BP 
participants, we will determine the modality they choose to transmit their home BP 
readings (e.g. via Bluetooth, manual log, phone, etc) 
 Differences in blood pressures between treatment groups as assessed by: (1) pre-
dialysis SBP and DBP; (2) post-dialysis SBP and DBP and (3) 44-hour intra-
dialytic ambulatory blood pressure monitoring from beginning to theend of the 
study (optional) 
6 
SUBJECT SELECTION 
6.1 
Study Population 
Subjects with ESRD on maintenance in center hemodialysis who meet the inclusion and 
exclusion criteria will be eligible for participation in this study.   
6.2 
Inclusion Criteria 
In order to be eligible to participate in this study, an individual must meet all of the 
following criteria: 
1. Provision of signed and dated informed consent form 
2. Undergoing in-center, thrice weekly hemodialysis for treatment of end stage renal 
disease 
3. Greater than 3 months since initiation of dialysis 
4. Aged 18 years or above  
5. Able to obtain a brachial blood pressure at dialysis and at home 
6.3 
Exclusion Criteria 
1. Pregnancy, anticipated pregnancy, or breastfeeding as this will  
require increase to more than three time a week dialysis and/or preclude use of some 
classes of blood pressure medications 
2.  Incarceration or institutionalized living which may prohibit measurement of home 
blood pressure 
3. Participation in another intervention study that may affect blood pressure 
4. Patients in whom systolic blood pressure is not measurable (e.g. those with left 
ventricular assist devices) 
5. Hypotension: average pre-dialysis systolic blood pressure <100 mmHg over last 2 
weeks prior to screening while not taking any blood pressure medications 
6. Life expectancy <4 months 
7. Anticipated living donor kidney transplant within 4 months 


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6.4 
Strategies for Recruitment and Retention 
 Target study sample size: Our target sample size is 50 participants (25 participants at 
UCSF and 25 participants at UW).  
 Source of participants: outpatient hemodialysis units affiliated with UCSF and UW or 
where UCSF and UW faculty practice.  
 We will use the Electronic Medical Record (EMR) or directly query dialysis 
healthcare providers at UCSF and UW to identify eligible participants. We may 
confer with the primary nephrologist prior to approaching the patient if there are 
concerns about the suitability of the patient to participate in a research study. 
 Incentives: Participants will be provided $25-50 per month for participation in the 
study, depending on the visit number and the site. 
 
7 
STUDY TREATMENTS 
7.1 
Method of Assigning Subjects to Treatment Groups 
Enrolled subjects, stratified by site, will be randomly assigned in a 1:1 allocation to one of 
2 groups (25 patients at both sites): (1) home SBP<140 mmHg and (2) in-center pre-
dialysis SBP<140 mmHg. Randomization will be in done via Redcap in random size 
blocks to minimize bias in randomization and to ensure balanced assignment at each site. 
Both groups will be followed in parallel. 
Prior to conducting any study-related activities, written informed consent and the Health 
Insurance Portability and Accountability Act (HIPAA) authorization must be signed and 
dated by the subject or subject’s legal representative.  If appropriate, assent must also be 
obtained prior to conducting any study-related activities. 
 
7.2 
Blinding 
Due to the nature of the intervention, the study will not be blinded to either the 
investigators nor the study participants. 
7.3 
Measuring Home SBP  
We will use the Microlife WatchBP Home A BT device.   
After appropriate training by study personnel, study participants will be asked to take their 
own BP at home every two weeks. 
 Home BP will be taken on a non-dialysis day 
 Participants will be instructed to obtain a BP measure in the morning on a non-
dialysis day (3 consecutive BP measures obtained at one sitting) 
 Participants will be instructed to obtain a BP measure in the evening on a non-
dialysis day (3 consecutive BP measures obtained at one sitting) 


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Participants will have several options to share the home blood pressure readings with the 
study team.  
• 
For participants with a smart phone, the BP readings can be automatically 
downloaded via Bluetooth to an app then to a secure cloud server. 
• 
Participants can download the readings from the home blood pressure device via 
USB drive and shared with the study team. 
• 
Participants can keep a paper log of home blood pressure readings to share with 
the study team. 
• 
Participants can text,phone or email the results to the study team. 
We will allow assistance from family members or other caregivers and work in other 
ways with study participants to minimize burden of data transmission. 
7.4         Measurement of In-Center Pre-Dialysis SBP 
Pre-dialysis BP will be taken by an automated BP device by dialysis unit staff using 
regular dialysis unit equipment.  
We will educate the dialysis unit staff and participants to allow patients to relax (ideally a 
5 minute rest) prior to BP being measured and that the BP cuff should be placed over bare 
arm or a thin garment. 
The pre-dialysis BP will be reviewed by the study team every 2 weeks.  
 
7.5 
Treatment Adherence 
Participants in both treatment arms will have regular contact with the study coordinator 
(scheduled approximately every 2 weeks), where they will be reminded/encouraged to 
take all prescribed anti-hypertensive medications and medication reconciliation will be 
performed. For participants in the home BP treatment arm, home BP readings will be 
reviewed and assessed for adherence. 
7.6 
Temporary Discontinuation 
Temporary discontinuation will be allowed in the study protocol in the event of 
hospitalization, travel out of town or other unavoidable breaks. Participants will be re-
evaluated at hospital discharge or return to regular maintenance dialysis unit and resume 
participation in the trial barring any clinical contraindications. This mimics how study 
intervention would be implemented in actual clinical practice. 
7.7 
Lost to Follow-Up 
A participant will be considered lost to follow-up if he or she fails to engage in 
participants contacts (either by phone or in the dialysis unit) of greater than 1 month and is 
unable to be contacted by the study site staff.  
 
The following actions must be taken if a participant fails to engage in contacts with the 
study team : 


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 The site will attempt to contact the participant and counsel the participant on the 
importance of maintaining the assigned contact 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. 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 PROCEDURES AND GUIDELINES:  
8.1 
Approach to blood pressure management 
For participants in the usual care treatment group, blood pressure readings measured for 
clinical purposes at the dialysis unit will be tracked, recorded and in response we will 
modify the dry weight and anti-hypertensive medications per algorithm below 
(including the date in which any adjustments to dry weight and medication dose were 
implemented).  
 
For participants in the home blood pressure treatment group, we will track and record 
the home blood pressure measures and modify the dry weight and anti-hypertensive 
mediations per algorithm below. 
 
The following approach will be used to achieve SBP <140 mmHg and >100 in both 
treatment groups, which will be implemented every 2 weeks. 
 
Dry weight adjustment (with counseling on dietary sodium and fluid intake if 
appropriate) 
 
Adjustment of standard anti-hypertensive medications (e.g. angiotensin 
converting enzyme [ACE] inhibitors/angiotensin receptor blockers 
[ARB][collectively referred to as RAAS inhibitors]; β-blockers; calcium channel 
blockers). The protocol will be as follows 
 
1. If SBP<100 mmHg: 
o Increase dry weight by 0.2-0.5 kg until patient euvolemic 
o If SBP still <100 mmHg, will titrate down/off patient’s existing 
medications in the following order: anti-adrenergic; vasodilators; alpha 
blockers; calcium channel blockers; β-blockers; RAAS inhibitors 
 
2. If SBP 100-140 mmHg: 
o No adjustment of dry weight or medications; recheck in two weeks 
 
3. If SBP>140 mmHg 
o Decrease dry weight by 0.2-0.5 kg until patient euvolemic 
o If SBP still >140 mmHg, will increase doses of patient’s existing 
medications in the following order: RAAS inhibitors; β-blockers; 
calcium channel blockers; alpha blockers; vasodilators; anti-adrenergic 
o If patient is at maximum tolerated doses of current medications and 
SBP>140 mmHg, will add doses (and titrate up) of new medication 


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classes in the following order (not duplicating classes with patient’s 
existing medications): RAAS inhibitors; β-blockers; calcium channel 
blockers; alpha blockers; vasodilators; anti-adrenergic. Choice of specific 
anti-hypertension medications within each class will prioritize those that 
have low dialyzability and are covered by the patient’s existing insurance 
coverage. The dialyzability characteristics of specific medications is 
outlined in the table below (from Georgianos and Agarwal CJASN 
201641):42-44 
 


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A Schedule of Events representing the required testing procedures to be performed for the 
duration of the study is diagrammed in Appendix 1. 


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8.2 
Clinical Assessments 
8.2.1 
Demographics  
Demographic information (date of birth, gender, race/ethnicity) will be recorded at the 
Screening visit. 
8.2.2 Medical History and Concomitant Medications 
Relevant medical history, including history of current disease and concomitant medication 
use (including dose, route and frequency of administration) will be recorded at screening 
visit and updated at all follow-up study visits. 
8.2.3 Blood pressure: Assessment of episodes and symptoms of intra-dialytic 
hypotension  
We will review the dialysis record approximately every 2 weeks for all study 
participants to determine frequency of intra-dialytic hypotension (IDH; defined as intra-
dialytic SBP<90 mmHg45). This will be obtained from the dialysis unit medical record 
and quantified as % of sessions with IDH over the 4-month study duration. For 
symptoms assessment, we will contact participants (in both arms) once approximately 
every 2 weeks.  Patients will be queried via interview (either phone or during dialysis) 
about adverse events noted during the past HD session(s) which will include symptoms 
of hypotension such as cramping (yes/no), dizziness/lightheadedness (yes/no) and 
fatigue (yes/no). We will also ask patients “how long did it take you to recover from 
your last dialysis treatment,” a validated question that is an important patient-centered 
outcome.46 Patient responses to this question will be reported in minutes. 
8.2.4 Adverse Events 
Information regarding occurrence of adverse events will be captured throughout the study. 
Outcomes in relation to study intervention will be recorded on the case report form (CRF). 
8.3 
Clinical Laboratory Measurements  
Standard clinical laboratory measures will be documented for the study at all study visits. 
The University of Washington site will be collecting 10 ml of plasma and 10 ml of serum 
for planned biomarker measurements at the completion of the study. The University of 
Washington site will also collect 5 ml of serum for pregnancy test for women of 
childbearing potential at the screening visit. 
9 
EVALUATIONS BY VISIT 
9.1   Visit 0: Screening visit 
1. Review the study with the subject and obtain written informed consent and HIPAA 
authorization 
2. Assign the subject a unique screening number. 
3. Record demographics data. 


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4. Record medical history, including a history of ESRD, dialysis access, dialysis 
initiation date and history of prior kidney transplants through participant 
questionnaires and review of the medical record 
5. Record concomitant medications through participant questionnaires and review of the 
medical record 
6. Record and review previous pre-dialysis blood pressures from the prior 2 weeks 
7. Record previous clinical laboratory values (with corresponding date) taken from the 
dialysis and other medical records 
8. Administer questionnaire of symptoms of hypotension during the last hemodialysis 
session(s): cramping (yes/no), dizziness/lightheadedness (yes/no), and fatigue 
(yes/no).  
9. Ask open-ended question: “How long did it take you to recover from your last dialysis 
session” (responses in minutes or hours) 
10. Obtain blood (5 ml) for serum pregnancy test for women of childbearing potential. 
 
9.2 
    Visit 1:  Baseline Visit 
1. Update information obtained at screening visit 
2. Record the following information from the dialysis records from the prior two weeks: 
estimated dry weight, pre-dialysis blood pressures, episodes of intra-dialytic 
hypotension 
3. Randomize participant to one of two study arms 
4. If participant is randomized to home BP arm, train participant on use and transmission 
of home BP measures 
5. Schedule subject for next study contact in approximately14 days, either during patient’s 
regularly scheduled dialysis or a telephone call  
6. Optional: Place 44-hour ambulatory blood pressure cuff and train patient on use (study 
team will also coordinate with patient return of 44-hour ambulatory blood pressure 
monitor.) Administer 44-Hour ABPM Experience Questionnaire. 
7. Blood sample collected at beginning of dialysis treatment via dialysis access and usual 
dialysis procedures (at UW only) 
 
 
9.3 
Visits 2-8 (occurring approximately every 2 weeks) 
1. Record any Adverse Experiences  
2. Review any home BP measures (if applicable) 
3. Concomitant medications review  
4. Updated medical history/interim events/interim hospitalizations 
5. BP medication review and assessment of adherence to BP medications 


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6. Review dialysis unit records: estimated dry weight, pre-dialysis blood pressures, 
episodes of intra-dialytic hypotension 
7. Record any updated laboratory values (with corresponding date) taken from the 
dialysis records 
8. Record vital signs, including weight and dialysis unit BP 
9. Administer questionnaire of symptoms of hypotension during the last hemodialysis 
session: cramping (yes/no), dizziness/lightheadedness (yes/no), and fatigue (yes/no).  
10. Ask open-ended question: “How long did it take you to recover from your last dialysis 
session” (responses in minutes or hours) 
11. If subject is a woman of child-bearing age, she will also be asked about possible 
pregnancy (UW only).  
12. Adjust estimated dry weight and medications as per study physician’s 
recommendations 
9.4 
Visit 9 (final study visit) 
1. Same procedures listed in for visits 2-8 
2. Blood sample collected at beginning of dialysis treatment via dialysis access and 
usual dialysis procedures (at UW only) 
3. Administer Home BP Device Experience Questionnaire. 
4.  Optional: Place 44-hour ambulatory blood pressure cuff and train patient on use 
(study team will also coordinate with patient return of 44-hour ambulatory blood 
pressure monitor). Administer 44-Hour ABPM Experience Questionnaire.  
 
10 ADVERSE EXPERIENCE REPORTING AND DOCUMENTATION 
10.1 Adverse Events 
An adverse event (AE) is any untoward medical occurrence during a clinical investigation 
and that does not necessarily have a causal relationship with the study intervention.  An 
AE is therefore any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom or disease that may or may not be associated with the administration of 
a study intervention.  
The study team will probe, via discussion with the subject and review of the medical 
record, for the occurrence of AEs during each subject visit and record the information in 
the site’s source documents.  Adverse events will be recorded in the patient CRF.  
Adverse events will be described by duration (start and stop dates and times), severity, 
outcome, treatment and relation to study intervention, or if unrelated, the cause. 
AE Severity 
AE severity will be classified as: 


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Table 1.  AE Severity Grading 
Severity (Toxicity Grade) 
Description 
Mild (1) 
Transient or mild discomfort; no limitation in activity; no medical 
intervention or therapy required. The subject may be aware of the sign 
or symptom but tolerates it reasonably well. 
Moderate (2) 
Mild to moderate limitation in activity, no or minimal medical 
intervention/therapy required. 
Severe (3) 
Marked limitation in activity, medical intervention/therapy required, 
hospitalizations possible. 
Life-threatening (4) 
The subject is at risk of death due to the adverse experience as it 
occurred. This does not refer to an experience that hypothetically 
might have caused death if it were more severe. 
 
AE Relationship to Study Intervention 
The relationship of an AE to the study intervention should be assessed using the following 
the guidelines in Table 2. 
Table 2.  AE Relationship to Study Intervention 
Relationship 
to Intervention 
Comment 
Definitely 
Previously known effect of intervention; or an event that follows a reasonable 
temporal sequence from administration of the intervention; that follows a known or 
expected response pattern to the suspected intervention; and that is not explained by 
any other reasonable hypothesis. 
Probably 
An event that follows a reasonable temporal sequence from administration of the 
intervention; that follows a known or expected response pattern to the suspected 
intervention; and that is unlikely to be explained by the known characteristics of the 
subject’s clinical state or by other interventions. 
Possibly 
An event that follows a reasonable temporal sequence from administration of the 
intervention; that follows a known or expected response pattern to that suspected 
intervention; but that could readily have been produced by a number of other factors. 
Unrelated 
An event that can be determined with certainty to have no relationship to the study 
intervention. 
10.2 Serious Adverse Experiences (SAE) 
An SAE is defined as any AE occurring at any dose that results in any of the following 
outcomes: 
 
death 
 
a life-threatening adverse experience 
 
inpatient hospitalization or prolongation of existing hospitalization 
 
a persistent or significant disability/incapacity 


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Other important medical events may also be considered an SAE when, based on 
appropriate medical judgment, they jeopardize the subject or require intervention to 
prevent one of the outcomes listed.  
 
10.2.1 Serious Adverse Experience Reporting 
Study sites will document all SAEs that occur (whether or not related to study drug) per 
UCSF CHR and UW IRB Guidelines.  The collection period for all SAEs will begin after 
informed consent is obtained and end after procedures for the final study visit have been 
completed. 
 
In accordance with the standard operating procedures and policies of the local Institutional 
Review Board (IRB), the site investigator will report SAEs to the IRB.   
   
We will collect data on potential adverse events from several sources and incorporate 
them into the adverse event database.  These sources include:   
 Reports from participants of any occurrences of concern to them, to be obtained 
from calls to toll-free or local study numbers provided in the Consent Form and 
included in all post-enrollment Contact Forms  
 Laboratory database and reports of new hospitalizations 
Adverse events data from the study-site specific call lines will be reviewed weekly, as will 
AE reports from all sources, by the site PI and site study clinician(s), any Serious Adverse 
Events that are identified will be reported promptly to the DSMB and IRB(s).  
10.2.2 Post-study Adverse Event 
We will continue to collect information on Adverse Events for up to 4 weeks after the 
study follow up period ends for all participants unless they ask us to not collect follow-up 
data. 
11 DISCONTINUATION AND REPLACEMENT OF SUBJECTS 
11.1 Early Discontinuation of Study Intervention  
A subject may be discontinued from study intervention at any time if the subject or the 
investigator (Sponsor) feels that it is not in the subject’s best interest to continue.  The 
following is a list of possible reasons for study treatment discontinuation:  
 
Subject withdrawal of consent  
 
Subject is not adherent with study procedures 
 
Adverse event that in the opinion of the investigator would be in the best interest of 
the subject to discontinue study treatment 
 
Protocol violation requiring discontinuation of study treatment 


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 
Lost to follow-up 
If a subject is withdrawn from treatment due to an adverse event, the subject will be 
followed and treated by the investigator until the abnormal parameter or symptom has 
resolved or stabilized.   
All subjects are free to withdraw from participation at any time, for any reason, specified 
or unspecified, and without prejudice. 
Reasonable attempts will be made by the investigator to provide a reason for subject 
withdrawals.  The reason for the subject’s withdrawal from the study will be specified in 
the subject’s source documents.  Subjects enrolled at least 1 month should be encouraged 
to come in for a final visit (and the procedures to be followed would include those for 
their next scheduled visit).   
11.2 Replacement of Subjects 
Subjects who withdraw from the study prior to 1 months will be replaced.   
12 PROTOCOL VIOLATIONS 
A protocol violation occurs when the subject or investigator (Sponsor) fails to adhere to 
significant protocol requirements affecting the inclusion, exclusion, subject safety and 
primary endpoint criteria.  Protocol violations for this study include, but are not limited to, 
the following: 
 
Failure to meet inclusion/exclusion criteria 
 
Failure by the study team to schedule every other week participant contact 
Failure to comply with Good Clinical Practice (GCP) guidelines will also result in a 
protocol violation. The UCSF and UW IRBs will determine if a protocol violation will 
result in withdrawal of a subject. 
When a protocol violation occurs, it will be discussed with the investigator and a Protocol 
Violation Form detailing the violation will be generated. This form will be signed by the 
investigator. A copy of the form will be filed in the site’s regulatory binder and in the 
Sponsor’s files. 
13 DATA SAFETY MONITORING 
The Data Safety Monitoring Board (DSMB) will review data relating to safety and 
efficacy, to conduct and review interim analyses, and to ensure the continued scientific 
validity and merit of the study, according to the Data Safety Monitoring Board Operations 
Manual and a DMC Charter to be established for this protocol. There will be one interim 
review conducted by the DMC for the purpose of monitoring study conduct and assessing 
patient safety.  Further details regarding the timing and content of the interim reviews is 
included in the statistical section below. 


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14 STATISTICAL METHODS AND CONSIDERATIONS 
Prior to the analysis of the final study data, a detailed Statistical Analysis Plan (SAP) will 
be written describing all analyses that will be performed.  The SAP will contain any 
modifications to the analysis plan described below.   
14.1 Data Sets Analyzed 
All patients who are randomized into the study will be included in the analysis. 
14.2 Demographic and Baseline Characteristics 
The following demographic variables at screening will be summarized by study treatment 
group including (but not limited to): race/ethnicity, gender, age, dialysis vintage (number 
of years on maintenance dialysis), comorbidity. 
14.3 Analysis of Primary Endpoint 
We will quantify the screen: enroll ratio. We will quantify rates of retention and 
adherence in each arm of the study and report characteristics of those lost to follow-up.  
We will quantify % of patients in the home BP arm who can successfully complete 
home BP training, % who can transmit every other weekhome BP readings in a timely 
manner to the study team via any method and % who successfully implement electronic 
transfer of data via Bluetooth/smartphone. 
Adverse events will be tabulated by treatment group and will include the number of 
patients for whom the event occurred, the rate of occurrence, and the severity and 
relationship to study intervention.  
We will determine frequency of excessively high or low blood pressures, frequency of 
intra-dialytic hypotension  and symptoms related to these in all enrollees. 
 
14.4 Analysis of Secondary Endpoints 
In both groups, we will use descriptive statistics (such as mean and standard deviation) to 
quantify changes in pre-dialysis blood pressure and 44-hour ABMP results at the end of 
the study.  
We will also describe patterns of dry weight target and blood pressure medication use 
(number and dosage).  
14.5 Sample Size and Randomization 
The target sample size is 50 participants (25 in each arm), which was chosen based on 
feasibility within the budget of these grants. This pilot study was designed to test study 
logistics and optimize study interventions, not to find statistically significant differences 
between the two arms 
Randomization will be in done in random size blocks to minimize bias in randomization 
and to ensure balanced assignment within strata. 


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15 DATA COLLECTION, RETENTION AND MONITORING 
15.1 Data Collection Instruments 
The investigator will prepare and maintain adequate and accurate source documents 
designed to record all observations and other pertinent data for each subject treated with 
the study drug.   
Study personnel at each site will enter data from source documents corresponding to a 
subject’s visit into the protocol-specific electronic Case Report Form (eCRF) OR paper 
CRF when the information corresponding to that visit is available.  For eCRFs: If a 
correction is required for an eCRF, the time and date stamps track the person entering or 
updating eCRF data and creates an electronic audit trail.  For paper CRFs:  If a correction 
is made on a CRF, the study staff member will line through the incorrect data, write in the 
correct data and initial and date the change. 
The investigator is responsible for all information collected on subjects enrolled in this 
study.  All data collected during the course of this study must be reviewed and verified for 
completeness and accuracy by the investigator.  A copy of the CRF will remain at the 
investigator’s site at the completion of the study. 
15.2 Data Management Procedures 
The data will be entered into a validated database.  The research team will be responsible 
for data processing.  Database lock will occur once quality assurance procedures have 
been completed. 
All procedures for the handling and analysis of data will be conducted using good 
computing practices meeting FDA guidelines for the handling and analysis of data for 
clinical trials. 
15.3 Data Quality Control and Reporting 
After data have been entered into the study database, a system of computerized data 
validation checks will be implemented and applied to the database on a regular basis. The 
study database will be updated in accordance with the resolved queries.  All changes to 
the study database will be documented. 
15.4 Archival of Data 
The database is safeguarded against unauthorized access by established security 
procedures; appropriate backup copies of the database and related software files will be 
maintained.  Databases are backed up by the database administrator in conjunction with 
any updates or changes to the database.   
At critical junctures of the protocol (e.g., production of final reports), data for analysis is 
locked and cleaned per established procedures. 
15.5 Availability and Retention of Investigational Records 
The investigator must make study data accessible to the DSMB, IRB, and Regulatory 
Agency (e.g., FDA) inspectors upon request.  A file for each subject must be maintained 


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that includes the signed Informed Consent, HIPAA Authorization and Assent Form and 
copies of all source documentation related to that subject.  The investigator must ensure 
the reliability and availability of source documents from which the information on the 
CRF was derived. 
All study documents (patient files, signed informed consent forms, copies of CRFs, Study 
File Notebook, etc.) must be kept secured for a period of two years following completion 
of the study.   
15.6 Monitoring 
Informal site visits will be conducted to assess completeness of record-keeping (e.g., 
consents), compliance with Good Clinical Practice (GCP) criteria, and assure that the 
protocol is being implemented consistently at the study site.  
15.7 Subject Confidentiality 
In order to maintain subject confidentiality, only a site number, subject number and 
subject initials will identify all study subjects on CRFs. 
16 ADMINISTRATIVE, ETHICAL, REGULATORY CONSIDERATIONS 
The study will be conducted according to the Declaration of Helsinki, Protection of 
Human Volunteers (21 CFR 50), Institutional Review Boards (21 CFR 56), and 
Obligations of Clinical Investigators (21 CFR 312). 
To maintain confidentiality, all laboratory specimens, evaluation forms, reports and other 
records will be identified by a coded number and initials only.  All study records will be 
kept in a locked file cabinet and code sheets linking a patient’s name to a patient 
identification number will be stored separately in another locked file cabinet.  Clinical 
information will not be released without written permission of the subject.  The 
investigator must also comply with all applicable privacy regulations (e.g., Health 
Insurance Portability and Accountability Act of 1996, EU Data Protection Directive 
95/46/EC). 
16.1 Protocol Amendments 
Any amendment to the protocol will be written by the investigators.  Protocol 
amendments cannot be implemented without prior written IRB approval except as 
necessary to eliminate immediate safety hazards to patients.  A protocol amendment 
intended to eliminate an apparent immediate hazard to patients may be implemented 
immediately, provided the IRBs are notified within five working days. 
16.2 Institutional Review Boards and Independent Ethics Committees 
The protocol and consent form will be reviewed and approved by the IRB of each 
participating center prior to study initiation.  Serious adverse experiences regardless of 
causality will be reported to the IRB in accordance with the standard operating procedures 
and policies of the IRB, and the investigator will keep the IRB informed as to the progress 
of the study.  The investigator will obtain assurance of IRB compliance with regulations. 


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Any documents that the IRB may need to fulfill its responsibilities (such as protocol, 
protocol amendments, consent forms, information concerning patient recruitment, 
payment or compensation procedures, or other pertinent information) will be submitted to 
the IRB.  The IRB’s written unconditional approval of the study protocol and the informed 
consent form will be in the possession of the investigator before the study is initiated. This 
approval must refer to the study by exact protocol title and number and should identify the 
documents reviewed and the date of review. 
Protocol and/or informed consent modifications or changes may not be initiated without 
prior written IRB approval except when necessary to eliminate immediate hazards to the 
patients or when the change(s) involves only logistical or administrative aspects of the 
study.  Such modifications will be submitted to the IRB and written verification that the 
modification was submitted and subsequently approved should be obtained.   
The IRB must be informed of revisions to other documents originally submitted for 
review; serious and/or unexpected adverse experiences occurring during the study in 
accordance with the standard operating procedures and policies of the IRB; new 
information that may affect adversely the safety of the patients of the conduct of the study; 
an annual update and/or request for re-approval; and when the study has been completed. 
16.3 Informed Consent Form  
Informed consent will be obtained in accordance with the Declaration of Helsinki, ICH 
GCP, US Code of Federal Regulations for Protection of Human Subjects (21 CFR 
50.25[a, b], CFR 50.27, and CFR Part 56, Subpart A), the Health Insurance Portability 
and Accountability Act (HIPAA, if applicable), and local regulations. 
The investigator will prepare the informed consent form, assent and HIPAA authorization 
and provide the documents to the Sponsor or designee for approval prior to submission to 
the IRB.  The consent form generated by the investigator must be approved by the IRB.  
The written consent document will embody the elements of informed consent as described 
in the International Conference on Harmonization and will also comply with local 
regulations. The investigator will send an IRB-approved copy of the Informed Consent 
Form to the Sponsor (or designee) for the study file. 
A properly executed, written, informed consent will be obtained from each subject prior to 
entering the subject into the trial.  Information should be given in both oral and written 
form and subjects (or their legal representatives) must be given ample opportunity to 
inquire about details of the study.  If appropriate and required by the local IRB, assent 
from the subject will also be obtained.  If a subject is unable to sign the informed consent 
form (ICF) and the HIPAA authorization, a legal representative may sign for the subject.   
A copy of the signed consent form (and assent) will be given to the subject or legal 
representative of the subject and the original will be maintained with the subject’s records. 
16.4 Publications  
The preparation and submittal for publication of manuscripts containing the study results 
shall be in accordance with a process determined by participating investigators.  The 
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laws, including, but not limited to, the Health Insurance Portability and Accountability 
Act of 1996.  
16.5 Investigator Responsibilities 
By signing the Protocol Agreement, the investigator agrees to: 
1. Conduct the study in accordance with the protocol and only make changes after 
notifying the IRB, except when to protect the safety, rights or welfare of subjects. 
2. Personally conduct or supervise the study. 
3. Ensure that the requirements relating to obtaining informed consent and IRB review 
and approval meet federal guidelines, as stated in § 21 CFR, parts 50 and 56. 
4. Report to the Sponsor or IRB any AEs that occur in the course of the study, in 
accordance with §21 CFR 312.64. 
5. Ensure that all associates, colleagues and employees assisting in the conduct of the 
study are informed about their obligations in meeting the above commitments. 
6. Maintain adequate and accurate records in accordance with §21 CFR 312.62 and to 
make those records available for inspection with the IRB. 
7. Ensure that an IRB that complies with the requirements of §21 CFR part 56 will be 
responsible for initial and continuing review and approval of the clinical study. 
8. Promptly report to the IRB  all changes in the research activity and all unanticipated 
problems involving risks to subjects or others. 
9. Seek IRB approval before any changes are made in the research study, except when 
necessary to eliminate hazards to the patients/subjects. 
10. Comply with all other requirements regarding the obligations of clinical investigators 
and all other pertinent requirements listed in § 21 CFR part 312. 
 


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CFFT TDN   Effective: 12 SEP 2007 
APPENDIX 1.   
 
VISIT 0 
SCREENING 
VISIT 
VISIT 1 
Baseline Visit 
VISITS 2-8 
(in person 
during 
regularly 
scheduled 
dialysis or 
phone call) 
14 (+/-7)  days 
apart 
              VISIT 9 
 
Informed Consent 
X 
 
 
 
Medical History 
X 
X 
X 
X 
Recording of vital signs, 
including blood pressure 
and weight 
X 
X 
X 
X 
Review of medical and 
dialysis records 
X 
X 
X 
X 
Medication review 
X 
X 
X 
X 
Record laboratory values 
X 
X 
X 
X 
Questionnaires on 
episodes and symptoms 
of high or low blood 
pressure  
X 
X 
X 
X 
Randomization 
 
X 
 
 
Teaching of home BP 
monitor 
 
X 
 
 
Reviewing BP 
medications and pre- and 
post-dialysis weights 
 
 
X 
X 
Review home BP 
readings (if applicable) 
 
 
X 
X 
Concomitant Medication 
Review 
 
 
X 
X 
Adjust EDW or BP 
medications 
 
 
X 
X 
Adverse Experiences 
 
 
X 
X 
44-hour ambulatory 
blood pressure monitor 
 
X 
 
X 
Blood draw 
 
X 
 
X 
 


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CFFT TDN   Effective: 12 SEP 2007 
REFERENCES 
 
1. 
Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Collaboration PS. Age-
specific relevance of usual blood pressure to vascular mortality: a meta-analysis of 
individual data for one million adults in 61 prospective studies. Lancet. 
2002;360(9349):1903-1913. 
2. 
Flack JM, Neaton J, Grimm R, Jr., et al. Blood pressure and mortality among men 
with prior myocardial infarction. Multiple Risk Factor Intervention Trial Research 
Group. Circulation. 1995;92(9):2437-2445. 
3. 
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4. 
Vamos EP, Harris M, Millett C, et al. Association of systolic and diastolic blood 
pressure and all cause mortality in people with newly diagnosed type 2 diabetes: 
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James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the 
management of high blood pressure in adults: report from the panel members 
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Wright JT, Williamson JD, Whelton PK, et al. A Randomized Trial of Intensive 
versus Standard Blood-Pressure Control. New Engl J Med. 2015;373(22):2103-
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Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for 
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Research, Clinical Cardiology, and Epidemiology and Prevention. Hypertension. 
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Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in 
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Locatelli F, Marcelli D, Conte F, et al. Survival and development of cardiovascular 
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Ok E, Asci G, Chazot C, Ozkahya M, Mees EJD. Controversies and problems of 
volume control and hypertension in haemodialysis. Lancet. 2016;388(10041):285-
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Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of 
cardiovascular risk factors in maintenance dialysis patients. Kidney international. 
2003;63(3):793-808. 
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Duranti E, Imperiali P, Sasdelli M. Is hypertension a mortality risk factor in 
dialysis? Kidney Int Suppl. 1996;55:S173-174. 
13. 
Zager PG, Nikolic J, Brown RH, et al. "U" curve association of blood pressure and 
mortality in hemodialysis patients. Kidney Int. 1998;54(2):561-569. 


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Cheung AK, Sarnak MJ, Yan G, et al. Atherosclerotic cardiovascular disease risks 
in chronic hemodialysis patients. Kidney Int. 2000;58(1):353-362. 
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Agarwal R. Blood pressure and mortality among hemodialysis patients. 
Hypertension. 2010;55(3):762-768. 
16. 
Kovesdy CP, Bleyer AJ, Molnar MZ, et al. Blood pressure and mortality in u.s. 
Veterans with chronic kidney disease: a cohort study. Ann Intern Med. 
2013;159(4):233-242. 
17. 
Robinson BM, Tong L, Zhang J, et al. Blood pressure levels and mortality risk 
among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. 
Kidney Int. 2012;82(5):570-580. 
18. 
Port FK, Hulbert-Shearon TE, Wolfe RA, et al. Predialysis blood pressure and 
mortality risk in a national sample of maintenance hemodialysis patients. Am J 
Kidney Dis. 1999;33(3):507-517. 
19. 
Inrig JK, Patel UD, Toto RD, Szczech LA. Association of blood pressure increases 
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Kidney Dis. 2009;54(5):881-890. 
20. 
Kalantar-Zadeh K, Kilpatrick RD, McAllister CJ, Greenland S, Kopple JD. Reverse 
epidemiology of hypertension and cardiovascular death in the hemodialysis 
population: the 58th annual fall conference and scientific sessions. Hypertension 
(Dallas, Tex. : 1979). 2005;45(4):811-817. 
21. 
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and death risk in hemodialysis patients. Am J Kidney Dis. 2006;48(4):606-615. 
22. 
Mazzuchi N, Carbonell E, Fernandez-Cean J. Importance of blood pressure control 
in hemodialysis patient survival. Kidney Int. 2000;58(5):2147-2154. 
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blood pressure and mortality in prevalent haemodialysis patients in the HEMO 
study. Journal of human hypertension. 2011;25(2):98-105. 
24. 
Bansal N, McCulloch CE, Rahman M, et al. Blood pressure and risk of all-cause 
mortality in advanced chronic kidney disease and hemodialysis: the chronic renal 
insufficiency cohort study. Hypertension. 2015;65(1):93-100. 
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Bolton K, Beddhu S, Campese VM, et al. K/DOQI clinical practice guidelines for 
cardiovascular disease in dialysis patients. Am J Kidney Dis. 2005;45(4):S7-S153. 
26. 
Harper J, Nicholas J, Webb L, Casula A, Williams AJ. UK Renal Registry 12th 
Annual Report (December 2009): Chapter 11 Blood Pressure Profile of Prevalent 
Patients Receiving Dialysis in the UK in 2008: national and centre-specific 
analyses. Nephron Clin Pract. 2010;115:C239-C260. 
27. 
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Canadian Society of Nephrology. J Am Soc Nephrol. 2006;17(3 Suppl 1):S1-27. 
28. 
Roberts MA, Pilmore HL, Tonkin AM, et al. Challenges in blood pressure 
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Guidelines for Management of Cardiovascular Diseases in Patients on Chronic 
Hemodialysis. Ther Apher Dial. 2012;16(5):387-435. 
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31. 
Alborzi P, Patel N, Agarwal R. Home blood pressures are of greater prognostic 
value than hemodialysis unit recordings. Clin J Am Soc Nephrol. 2007;2(6):1228-
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Agarwal R. Managing hypertension using home blood pressure monitoring among 
haemodialysis patients-a call to action. Nephrology, dialysis, transplantation : 
official publication of the European Dialysis and Transplant Association - 
European Renal Association. 2010;25(6):1766-1771. 
33. 
Agarwal R, Andersen MJ, Bishu K, Saha C. Home blood pressure monitoring 
improves the diagnosis of hypertension in hemodialysis patients. Kidney Int. 
2006;69(5):900-906. 
34. 
Bansal N, McCulloch CE, Lin F, et al. Blood Pressure and Risk of Cardiovascular 
Events in Patients on Chronic Hemodialysis: The CRIC Study (Chronic Renal 
Insufficiency Cohort). Hypertension. 2017;70(2):435-443. 
35. 
Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC, Barre PE. Impact of 
hypertension on cardiomyopathy, morbidity and mortality in end-stage renal 
disease. Kidney Int. 1996;49(5):1379-1385. 
36. 
Foley RN. Cardiac disease in chronic uremia: can it explain the reverse 
epidemiology of hypertension and survival in dialysis patients? Seminars in 
dialysis. 2004;17(4):275-278. 
37. 
Fagard RH, Pardaens K, Staessen JA, Thijs L. The pulse pressure-to-stroke index 
ratio predicts cardiovascular events and death in uncomplicated hypertension. J Am 
Coll Cardiol. 2001;38(1):227-231. 
38. 
Burton JO, Jefferies HJ, Selby NM, McIntyre CW. Hemodialysis-induced repetitive 
myocardial injury results in global and segmental reduction in systolic cardiac 
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39. 
Burton JO, Jefferies HJ, Selby NM, McIntyre CW. Hemodialysis-induced cardiac 
injury: determinants and associated outcomes. Clin J Am Soc Nephrol. 
2009;4(5):914-920. 
40. 
McIntyre CW, Burton JO, Selby NM, et al. Hemodialysis-induced cardiac 
dysfunction is associated with an acute reduction in global and segmental 
myocardial blood flow. Clin J Am Soc Nephrol. 2008;3(1):19-26. 
41. 
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43. 
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Patients Receiving Hemodialysis. J Am Soc Nephrol. 2015;26(4):987-996. 
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after a hemodialysis session: a simple health-related quality of life question that is 
reliable, valid, and sensitive to change. Clin J Am Soc Nephrol. 2006;1(5):952-959. 
 

ICF_002.pdf: 
IRB NUMBER: 16-20963
IRB APPROVAL DATE: 07/27/2018
IRB EXPIRATION DATE: 01/03/2019
 
PAGE 1 OF 8 
JUNE 27TH, 2018, VERSION 1.3
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
 
Study Title: The Blood Pressure Lowering in Dialysis Trial (BOLD trial) 
 
Research Project 
Director: 
Chi-yuan Hsu, M.D., Professor and Chief, UCSF Division of 
Nephrology 
533 Parnassus Ave, Room U404, San Francisco, CA.   
Phone:  415.353.2379; e-mail:  hsuchi@medicine.ucsf.edu  
 
Study Coordinators: 
Joanne Batt, Phone:  415.502.1470;  
email: joanne.batt@ucsf.edu  
 
Farshad Palad, Phone: 415-476-1104; 
email: farshad.palad@ucsf.edu 
 
Zijin Chen, Phone 628-777-8355  
Email: zijin.chen@ucsf.edu  
 
 
This is a clinical research study.  Your study doctor, Chi-yuan Hsu, M.D., from the UCSF 
Department of Medicine, Division of Nephrology and/or his research team, will explain the 
study to you. 
 
Research studies include only people who choose to take part.  Please take your time to make 
your decision about participating.  You may discuss your decision with your family and friends 
and with your health care team.  If you have any questions, you may ask your study doctor. 
 
You are being asked to take part in this study because you have kidney disease and require 
chronic hemodialysis treatment. 
 
Why is this study being done? 
 
The purpose of this pilot study is to test if it is possible to adjust dry weight target and blood 
pressure medication to achieve systolic blood pressure <140 mmHg among hemodialysis patients 
measured in two different settings--at the dialysis unit (before dialysis treatment) or at home. We 
hope this pilot study will lead to a larger scale study to examine whether such different blood 
pressure management will improve clinical outcomes. 
 
As many dialysis patients know, the conventional concept for “dry weight” is your normal 
weight without any extra fluid in your body. 
 
Who pays for this study? 
 


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IRB EXPIRATION DATE: 01/03/2019
 
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JUNE 27TH, 2018, VERSION 1.3
This study is being paid for by research grants from the U.S. Federal Government (National 
Institutes of Health) and by Satellite Healthcare, a not-for-profit dialysis company. 
  
How many people will take part in this study? 
 
About 50 people will take part in this study total (counting both San Francisco and Seattle study 
participants). In San Francisco, this study will take place at the dialysis centers where UCSF 
doctors see patients. 
 
In Seattle, this study will take place at the dialysis centers where our collaborating University of 
Washington doctors see patients. 
 
What will happen if I take part in this research study? 
 
You will be selected randomly (i.e. by chance only) to be in one of two groups. 
In Group 1, we will aim to keep the systolic blood pressure (upper reading) measured at the 
dialysis unit (before the start of dialysis) below 140 mmHg.  In Group 2, we will aim to keep the 
systolic blood pressure (upper reading) measured at home below 140 mmHg. 
 
In both groups, dry weight target and blood pressure medication adjustment will be made to 
achieve target blood pressure. 
Before you begin the main part of the study... 
You will be asked a series of questions about your health and your symptoms related to blood 
pressure.  We will also review your medical record for additional information to see if you 
qualify for the study. 
During the main part of the study... 
If you qualify and choose to take part, then you will be "randomized" into one of the study 
groups described below.  Randomization means that you are put into a group by chance.  A 
computer program will place you in one of the groups.  Neither you nor your doctor can choose 
the group you will be in.  You will have an equal chance of being placed in any group. 
If you are in group 1: Your blood pressure measured at the dialysis unit before the start of 
dialysis will be targeted for treatment.  This is the current approach many doctors take and it is 
supported by guidelines and opinion leaders (although most acknowledge the evidence 
supporting this approach is not strong).  The target will be systolic blood pressure <140 mmHg. 
The study team and your regular nephrologist/health care providers will work together to adjust 
your dry weight target or blood pressure medications. 
 
If you are in group 2: Your blood pressure measured outside of the dialysis unit will be targeted 
for treatment. This is based on new research that blood pressure measured outside of the dialysis 
unit is likely more important than blood pressure measured at the dialysis unit. You will be given 
a blood pressure monitor and asked to measure your blood pressure at home and transmit the 
readings to the study team (potentially via Bluetooth and a smart phone).  You will take your 


IRB NUMBER: 16-20963
IRB APPROVAL DATE: 07/27/2018
IRB EXPIRATION DATE: 01/03/2019
 
PAGE 3 OF 8 
JUNE 27TH, 2018, VERSION 1.3
blood pressure at home morning and evening on one non-dialysis day every 2 weeks (the 
machine automatically averages 3 readings per sitting).The target is also systolic blood pressure 
<140 mmHg. The study team and your regular nephrologist/health care providers will work 
together to adjust your dry weight target or blood pressure medications. 
In both groups, you will check in with the study staff every 2 weeks, either by phone or at the 
dialysis unit, to answer a series of questions about symptoms related to dialysis and blood 
pressure such as cramping or dizziness.   
Optional for either group: At the beginning and at the end of the study, you can choose to wear a 
blood pressure monitor for 44 hours. It will take your blood pressure at regular intervals during 
this time. Changes in 44-hour averaged blood pressure from beginning to end of the study will 
give us more information about the impact of being in group 1 or group 2.   
All other aspects of your care will remain unaffected. 
Study location: All study procedures will be done at your regular dialysis unit or at home. 
Study Plan  
Another way to find out what will happen to you during the study is to read the chart below. Start 
reading at the top and read down the list, following the lines and arrows. 
 
Randomize 
(You will be in Group 1 or Group 2) 
 
Group 1 
Blood pressure measurements 
taken in dialysis unit only;  
 
target systolic blood pressure 
measured at the dialysis unit before 
the start of dialysis to <140 mmHg 
though dry weight and medication 
adjustments 
 
Group 2 
Blood pressure measurements at home 
(morning and evening on a non-dialysis day 
every 2 weeks); 
 
target systolic blood pressure measured at 
home to <140 mmHg though dry weight 
and medication adjustment 
As you may know, adjustment of dry weight target and blood pressure medication dose are the 
two main ways by which doctors can influence blood pressure levels in patients on 
hemodialysis. Extra fluid in the body is an important reason patients have high blood pressure. 


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IRB EXPIRATION DATE: 01/03/2019
 
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JUNE 27TH, 2018, VERSION 1.3
In either group, if your blood pressure is above goal (i.e. too high), we will gently try to remove 
more fluid while you are on dialysis and encourage less intake of salt and water (i.e. targeting a 
lower dry weight).  Your try weight target will be adjusted by small amounts (e.g. by 0.5 to 1 lb 
every other week).  If this is not enough, we will increase your blood pressure medications, also 
not more frequently than every other week. The changes in blood pressure medication dosage 
will be within standard clinical practice dose changes.  Your dry weight target and blood 
pressure medications will not be adjusted at the same time.  We will only do one or the other. 
In either group, if you blood pressure is below goal (i.e. too low), we will gently try to 
remove less fluid while you are on dialysis (i.e. targeting a higher dry weight) if the study team 
and your nephrologist think you do not have enough fluid in your body. This will also occur by 
small amounts (e.g. 0.5 to 1 lb each time). Otherwise, your blood pressure medications will be 
decreased. 
The study chart below summarizes the procedures: 
 
VISIT 0 
 Screening 
Visit  
VISIT 1 
Baseline Visit 
VISITS 2-8 
(in person during 
regularly scheduled 
dialysis or phone call) 
14 (+/-7)  days apart 
              
VISIT 9 
 
Informed Consent 
X 
 
 
 
Research team review of 
medical/dialysis records 
X 
X 
X 
X 
Questionnaires on episodes and 
symptoms of high or low blood 
pressure  
X 
 
X 
X 
Randomization 
 
X 
 
 
Teaching of home BP monitor (if 
applicable) 
 
X 
 
 
Review home BP readings (if 
applicable) 
 
 
X 
X 
Administer home BP monitor 
experience questionnaire (if 
applicable) 
 
 
 
X 
Adjust dry weight or blood pressure 
medications 
 
 
X 
X 
44-hour ambulatory blood pressure 
monitor (optional) and administer 
44-hour ambulatory blood pressure 
monitor experience questionnaire 
(if applicable) 
 
X 
 
X 
How long will I be in the study? 
You will be in this study for 5 months. We would like to keep track of your medical condition 
for up to one month after the end of the study. We would like to do this by calling you on the 
telephone to see how you are doing to helps us look at the long-term effects of the study. 


IRB NUMBER: 16-20963
IRB APPROVAL DATE: 07/27/2018
IRB EXPIRATION DATE: 01/03/2019
 
PAGE 5 OF 8 
JUNE 27TH, 2018, VERSION 1.3
Can I stop being in the study? 
Yes. You can decide to stop at any time. Tell the study team (Dr. Hsu and his colleagues) if you 
are thinking about stopping or decide to stop. He or she will tell you how to stop your 
participation safely.  
The study doctor may stop you from taking part in this study at any time if he/she believes it is in 
your best interest, if you do not follow the study rules, or if the study is stopped. 
What side effects or risks can I expect from being in the study? 
You may have side effects while on the study. Everyone taking part in the study will be watched 
carefully for any side effects. However, doctors don't know all the side effects that may happen.  
Side effects may be mild or very serious. You should talk to your study doctor about any side 
effects you experience while taking part in the study. 
Risks and side effects related to the changes in dry weight and blood pressure medications 
include those which are: 
Likely  
 
Dizziness/lightheadedness 
 
Fatigue 
 
Cramping during dialysis 
Possible  
 
Erectile dysfunction 
Rare but serious 
 
Passing out/loss of consciousness due to excessively low blood pressure  
 
Trouble breathing due to excessively high blood pressure 
Unknown Risks: The new approach to blood pressure management may have side effects that 
no one knows about yet.  The researchers will let you know if they learn anything that might 
make you change your mind about participating in the study. 
 
 
For more information about risks and side effects, ask your study doctor. 
Are there benefits to taking part in the study? 
If you are in the group that receives the home blood pressure monitor and it proves to treat your 
blood pressure with fewer side effects than standard therapy, you may benefit from participating 
in the study, but this cannot be guaranteed. 


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IRB APPROVAL DATE: 07/27/2018
IRB EXPIRATION DATE: 01/03/2019
 
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JUNE 27TH, 2018, VERSION 1.3
If you are in the group whose blood pressure is being managed based on blood pressure 
measured at the dialysis unit, you are getting standard therapy that the other group is not. 
In both groups, your will learn more about blood pressure treatment.  You will get a better 
understanding of how your blood pressure changes over time if you choose to wear the blood 
pressure monitor for 44 hours. 
This study will help doctors learn more about how to best manage blood pressure among 
hemodialysis patients and it is hoped that this information will help in the treatment of future 
patients with kidney failure. 
What other choices do I have if I do not take part in this study? 
If you do not take part in this study, you will receive medical care as usual. Participation in this 
study is completely voluntary. 
How will information about me be kept confidential? 
 
Participation in research involves some loss of privacy.  We will do our best to make sure that 
information about you is kept confidential, but we cannot guarantee total privacy.  Some 
information from your medical records will be collected and used for this study.  If you do not 
have a UCSF medical record, one will be created for you.  Your signed consent form and some 
of your research tests will be added to your UCSF medical record.  Therefore, people involved 
with your future care and insurance may become aware of your participation and of any 
information added to your medical record as a result of your participation.  Your personal 
information may be given out if required by law.  If information from this study is published or 
presented at scientific meetings, your name and other personal information will not be used. 
Authorized representatives from the following organizations may review your research data for 
the purpose of monitoring or managing the conduct of this study: 
 Representatives of the National Institutes of Health  
 Representatives of the Satellite Healthcare 
 Representatives of the University of California 
Will any research-related procedures be billed to me? 
No.  The sponsor has agreed to pay for all procedures associated with this research study (e.g. 
cost of home blood pressure device, cost of 44-hour blood pressure monitor); you or your insurer 
will not be billed.   
 
You will continue to pay for your blood pressure medications as you were doing before 
participating in the study. We will be adjusting the dosages of the medications you are already on 
and if new medications are added, we will work with your nephrologist to select ones with 
favorable coverage by your insurance. 


IRB NUMBER: 16-20963
IRB APPROVAL DATE: 07/27/2018
IRB EXPIRATION DATE: 01/03/2019
 
PAGE 7 OF 8 
JUNE 27TH, 2018, VERSION 1.3
Will I be paid for taking part in this study? 
In return for your time, effort and travel expenses, you will be paid $30 for each month you are 
in the study, through until Visit 9 in study chart above.  
 
If you choose to also wear the blood pressure monitor for 44 hours at the beginning and at the 
end of the study, you will receive an additional $30 the first time and $30 the second time. 
What happens if I am injured because I took part in this study? 
It is important that you tell your study doctor, Dr. Hsu, if you feel that you have been injured 
because of taking part in this study. You can tell the doctor in person or call him at (415) 353-
2379. 
Treatment and Compensation for Injury:  If you are injured as a result of being in this 
study, the University of California will provide necessary medical treatment.  The costs 
of the treatment may be billed to you or your insurer just like any other medical costs, or 
covered by the University of California, depending on a number of factors.  The 
University and the study sponsor do not normally provide any other form of 
compensation for injury.  For further information about this, you may call the office of 
the Institutional Review Board at 415- 476-1814.   
What are my rights if I take part in this study? 
Taking part in this study is your choice. You may choose either to take part or not to take part in 
the study. If you decide to take part in this study, you may leave the study at any time. No matter 
what decision you make, there will be no penalty to you and you will not lose any of your regular 
benefits. Leaving the study will not affect your medical care. You can still get your medical care 
from our institution and physicians.  
We will tell you about new information or changes in the study that may affect your health or 
your willingness to continue in the study. 
In the case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form. 
Who can answer my questions about the study? 
You can talk to your study doctor about any questions, concerns, or complaints you have about 
this study.  Contact your study doctor, Chi-yuan Hsu, MD at 415-353-2379. 
If you wish to ask questions about the study or your rights as a research participant to someone 
other than the researchers or if you wish to voice any problems or concerns you may have about 
the study, please call the office of the Institutional Review Board at 415-476-1814.    


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IRB APPROVAL DATE: 07/27/2018
IRB EXPIRATION DATE: 01/03/2019
 
PAGE 8 OF 8 
JUNE 27TH, 2018, VERSION 1.3
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time.  
************************************************************ 
 
CONSENT 
 
You have been given copies of this consent form and the Experimental Subject's Bill of Rights to 
keep. 
 
You will be asked to sign a separate form authorizing access, use, creation, or disclosure of 
health information about you. 
 
PARTICIPATION IN RESEARCH IS VOLUNTARY. You have the right to decline to 
participate or to withdraw at any point in this study without penalty or loss of benefits to which 
you are otherwise entitled. 
 
If you wish to participate in this study, you should sign below. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
Participant's Signature for Consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
Person Obtaining Consent