Pilot to Examine Risk and Feasibility of Remote Management of BP From CKD Through ESRD
Phase: NA
Conditions: Chronic Kidney Disease, Bloodpressure, Hypertension
Sponsor: University of California, San Francisco

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Intensive home blood pressure lowering in advanced chronic kidney disease: a pilot 
randomized controlled trial  
Study Protocol 
NCT02975505  
Document date:  February 13, 2025

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Study design 
This pilot study is a non-blinded randomized controlled trial investigating the safety and 
feasibility of strict blood pressure control in patients with advanced CKD. Patients will be 
randomized in 2:1 ratio to intervention (home SBP target < 120 mmHg) or usual care (home 
SBP target 130-140 mmHg) until 75 patients are enrolled, and then subsequently patients will 
be randomized in 1:1 ratio to intervention or usual care. Antihypertensive medications will be 
titrated as needed to achieve target home SBPs over the course of 4 months and maintained 
thereafter until study closeout (see Figure 1).  Biannual visits are conducted after month 12.   
Study population 
All patients are recruited from the University of California San Francisco nephrology clinics. 
Inclusion and exclusion criteria are as follows: 
Inclusion criteria: 
1.
> 18 years of age
2. English-speaking
3. Patients with advanced CKD who meet the eGFR criteria defined as either
a. at least two eGFRs ≤30 mL/min/1.73m2 in the last three months
b. a prior diagnosis of CKD and at least one eGFR ≤30 mL/min/1.73m2 in the last
three months.
4. Presence of elevated BP, defined as receipt of one or more antihypertensive agents or
an office SBP>140 mmHg at the time of the screening visit. If the participant is not on
antihypertensive medications, they must have an average home SBP>130 mmHg during
the first week of the study when baseline home BPs are ascertained.
5. Participants must have a mid-arm circumference between 22-37 cm and access to a
smart phone or tablet in order to use the Bluetooth-enabled home BP device,
QardioArm©.

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Exclusion criteria:  
Patients are excluded if they: 
1. are planning to become pregnant or are currently pregnant
2. are marginally housed due to concerns regarding follow-up
3. are institutionalized or a prisoner
4. are actively participating in a different interventional trial that may affect blood pressure
5. are actively abusing illicit drugs and alcohol
6. have a history of poor compliance
7. take >5 antihypertensive medications (including diuretics) at maximum doses
8. have cognitive impairment and are unable to follow instructions regarding home BP
measurement during screening visit
If patients meet all inclusions and exclusion criteria, we will check with their nephrology 
providers prior to approaching participants to ensure their candidacy in our study.  
Baseline Visit 
During the baseline visit, participant eligibility is confirmed, written consent is obtained, 
and demographic, co-morbidity, and laboratory data are collected. A brief physical examination 
is performed and three automated office BP readings in the seated position followed by two 
standing BP readings are recorded one minute apart after five minutes of quiet rest. At the 
baseline visit, enrollees are provided with a QardioArm© device and trained to use the device to 
take standardized home BP measurements.  
Participants are asked to take home BPs for a one-week baseline period to ensure 
continued eligibility and compliance with our protocol prior to randomization, with a minimum of 
6 readings required over the one-week period. Participants are also asked to complete 24-hour 
ambulatory blood pressure monitoring (ABPM) during their baseline period. Patients who refuse 
to undergo 24-hour ABPM are not excluded from study.  

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Randomization 
Eligible patients who complete the one week of baseline home readings will be 
randomized to either a home SBP target of <120 mmHg (intervention group) or 130-140 mmHg 
(usual care group) in 2:1 ratio until 75 participants are enrolled, and participants will be 
subsequently randomized in 1:1 ratio thereafter.  The rationale for the 2:1 ratio for the first 75 
patients is to ensure that we initially capture enough safety data on participants randomized to 
intervention, but we plan to transition to 1:1 ratio randomization thereafter. We will conduct a 
sensitivity analysis comparing the effect during the 2:1 randomization phase of the trial and 1:1 
phase to determine if there is an interaction between the intervention and the phase of the trial. 
Once patients are screened and deemed eligible, study personnel will notify 
nephrologists of their patients’ eligibility and obtain assent for patient participation in the trial 
prior to randomization. Stratified permuted-block randomization will be performed with 
stratification by diabetes status in order to ensure that patients with diabetes who have 
previously been excluded from many trials of intensive BP lowering (8–10) are represented in 
our pilot study. Investigators will be blinded to the ordering of the randomization blocks and their 
respective sizes.  The generation of allocation sequence is performed by and only accessible to 
the study coordinator for assignment of participants to the intervention and not accessible to 
investigators. Patients are contacted via phone or secure messaging to begin active titration of 
their antihypertensive regimens to achieve their assigned target SBPs after randomization. 
Home blood pressure monitor 
QardioArm© is a wireless Bluetooth-enabled home BP monitor that is validated by the 
European Society of Hypertension Protocol and the American Heart Association (31) and has a 
strong direct linear correlation (r=.96) with the previously validated and widely accepted Omron 
M3© BP device (32). The device is compatible with most smartphones and allows for real-time 

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wireless transmission of BP readings through an online phone application. The device is also 
accompanied by a secure platform used by providers for BP data transmission, monitoring, 
download, and storage. All participants are provided a device at no cost, and Bluetooth linkage 
between the device and smartphone are setup by study personnel at the baseline visit.  
Office BP readings during study visits 
Office BPs are measured at the baseline, 2, 4, 8, and 12-month study visits (Figure 1), 
and every six months thereafter. Participants are seated quietly in a room with the study 
coordinator for 5 minutes before BPs are taken. Three measurements are taken one minute 
apart. Participants are then be asked to stand for two minutes and two standing BPs are 
recorded one minute apart. One study coordinator will be present during all office BP 
measurements.  
Intervention 
Blood Pressure Targets 
We have chosen to target home SBP, as opposed to mean arterial pressure (MAP) or 
diastolic BP (DBP) based primarily on the CV and mortality benefits seen recently in SPRINT (8) 
and data that suggest that SBP is a stronger predictor of ESKD risk and CV disease than DBP 
or MAP (24,33,34). Our usual care group will be treated to home SBP targets of 130-140 mmHg 
(equivalent to office SBP of 135-145 mmHg) because this was the range of BPs that screened 
patients had at baseline enrollment under routine care. During routine clinical care, any non-
study provider can titrate antihypertensive agents as per their preference outside of the study 
protocol based on the clinic BP readings and other data available to them, and such titrations 
are noted and will be accepted by the study team.  Home BP readings are made readily 
available to non-study providers upon request, and all nephrology clinic providers are alerted of 
patient enrollment in the study and the assigned BP target following randomization.    

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Home blood pressure readings 
Participants are asked to measure their BPs at home on any three days of the week. For 
each day, participants take 3 readings in the morning and 3 in the evening. Participants are 
instructed to rest for 5 minutes before taking readings and sit quietly for 1 minute in between 
readings. Weekly home BP averages are calculated from the most recent 18 readings in a given 
week. Antihypertensive medications will be titrated by study investigators based on the average 
of the most recent 18 home BP measurements received, with a minimum of 6 required readings 
per week to be considered sufficient for any changes to medications. An insufficient number of 
measurements will prompt contact with the participant to increase the number of readings. 
Antihypertensive Therapy Titration Intervention 
Antihypertensive medications are titrated during the first 4 months to achieve target 
home SBP levels in both the intervention and usual care groups if home BP readings are not 
already within the target range. The antihypertensive therapy titration intervention will be 
individualized according to each patient’s medical history, current medication regimen, and
medication preference as specified by their nephrologist. Participants’ referring nephrologist will
be informed of their participation at the time of enrollment and asked to indicate which BP 
agents they would prefer to withdraw or add if SBP is outside of target according to their own 
practice patterns. Doses of current antihypertensive agents may be preferentially increased or 
decreased first depending on patient’s home BP readings relative to their target SBP. This will 
be the first-line approach to avoid introduction of multiple new medications if doses of current 
medications are not yet optimized.  New agents may be prescribed or discontinued after careful 
consideration of patient’s medical history and nephrologist’s input. Combination drugs will be 
acceptable but only used if suggested by the participant’s nephrologist, as there may be cost
barriers to the use of combination drugs. Although every antihypertensive treatment regimen will 

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likely differ for each participant, the suggested order of antihypertensive agent titration (if the 
nephrologist does not indicate a specific preference) will be angiotensin receptor blockers 
(ARBs) or angiotensin-converting enzyme inhibitors (ACEi) as first-line therapy, followed by (in 
order of preference) diuretics, calcium-channel blockers, beta-blockers, vasodilators/nitrates, 
sympatholytics, alpha-blockers, and potassium-sparing diuretics. See Figure 2 for the 
antihypertensive medication titration protocol. 
We will permit up to a 30% increase in serum creatinine level after ACEi/ARB initiation or 
uptitration of dosages of other antihypertensive medications, in accordance with traditional 
guidelines and published literature (35,36). For patients who experience >30% increase in 
serum creatinine, the ACEi/ARB dose or other antihypertensive medication will be reduced, with 
plans for a repeat serum creatinine within 2 weeks.  If the serum creatinine continues to be 
elevated, then the ACEi/ARB will be discontinued.  We will also respect the opinion of the 
patient’s nephrologist on this issue. If a nephrologist is concerned about any rise in serum 
creatinine, we will reduce or discontinue the drug.  We will then proceed with the next suggested 
class of antihypertensive agents to help achieve the target blood pressure. 
During the first 8 months of the study, participants will be contacted every other week by 
study coordinators to note any adverse events including dizziness, falls, syncope, 
hospitalizations, emergency room visits, acute kidney injury, CV events, or allergic reactions, as 
well as adherence to medication regimen and medication side effects such as diuresis, 
impotence, cough, lack of energy and sleepiness, lightheadedness on standing, or headaches.   
Laboratory Tests 
Basic metabolic panel and urine chemistry laboratory tests are obtained at baseline and 
at months 1, 2, 4, 8, 12, and every six months thereafter but timed as closely to clinical 
laboratory tests as possible (to avoid additional burden on participants) in a pragmatic 
approach. Labs are closely monitored by study investigators and medications titrated 

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accordingly to ensure the safety of all participants. Additional laboratory testing is performed as 
needed. 
Follow-Up Timeline 
The timeline of study visits during the one-year of follow-up is outlined in Figure 1. 
Participants are instructed to take weekly home BP readings for the first 4 months of the study, 
or until target SBP levels are achieved for two consecutive weeks. Once participants reach 
target SBP levels, home BP readings can be taken on a monthly basis over a one-week period 
each month. If participants maintain their target SBP levels after 8 months, home BP readings 
can be taken every two months thereafter. Participants will maintain their respective SBP target 
levels for the remainder of the study after month 8. If mean weekly SBP readings are > 4 mmHg 
outside the target range, antihypertensive therapy titration is resumed weekly until target SBP 
levels are achieved again for two consecutive weeks.  
Participants are seen in person at Months 2, 4, 8, and 12, and every 6 months 
thereafter, but visits will be timed as close to their clinical visits as possible to avoid additional 
burden on participants in a pragmatic approach.  In-person follow-up visits consist of a brief 
physical exam, office BP readings which will be obtained and used to calibrate the QardioArm© 
device to ensure accuracy of its readings, and laboratory testing. Patients will be contacted 
throughout the study via phone or secure text messages depending on patient preference. 
Adherence to antihypertensive therapy treatment will be assessed by administering a 
questionnaire during every in-person visit and follow-up phone call to ask participants if they are 
taking antihypertensive medications as prescribed and if they missed any doses since last 
follow-up. Adverse events (including emergency room visits or hospitalizations) and onset of 
ESKD, defined as initiation of chronic dialysis or receipt of kidney transplant, are also 
ascertained during follow-up.  Participants will be followed indefinitely unless they choose to 
disenroll from the study or are lost to follow-up. 

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Outcomes measures 
 
The primary outcome will be feasibility of achieving at least a 6 mmHg separation 
between intensive BP control and usual BP control arms at month 8.   A secondary outcome will 
be the difference in BP between the two treatment strategies at study closeout.  Adherence to 
home BP monitoring will be measured by the number of weeks participants successfully 
complete the minimum number of home readings.  
Safety of our intervention will also be a secondary outcome and will be determined by a 
composite of adverse events including hyperkalemia (K ≥ 6.0 meq/L), self-reported falls, 
syncope, or acute kidney injury (AKI) requiring emergency room visit or hospitalizations. 
Discharge summaries from emergency room visits and hospitalizations in patient health records 
will be reviewed and events adjudicated by two study investigators.  In addition, onset of ESKD 
will not be a censoring event; patients will be encouraged to continue to check home BPs 
following transplant or dialysis, but no study-driven active titration of antihypertensive agents will 
occur after ESKD onset.  
 
Statistical analysis  
 
Safety outcomes, or rates of adverse events, will be tallied using simple proportions and 
descriptive statistics. Intention-to-treat analysis will be performed. Stratified analyses by 
diabetes status will be performed given the lack of robust trial data to support intensive BP 
lowering in patients with diabetes. We will also test for differences in the composite rates of 
hospitalizations, emergency room visits, and hyperkalemia in the two arms.  We will explore 
differences in the rates of ESKD or cardiovascular events and determine if there is any effect 
modification of the intervention by level of proteinuria or by diabetes. For patients lost to follow-
up, we plan to use chained multiple imputation to perform analyses. 
 
Sample size rationale 
 

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Randomizing 96 participants to strict vs usual BP control will provide 80% power (with 2-
sided α of 0.05) to detect a 6-mmHg difference in SBP (with SD difference of 10 mmHg) 
between the two arms at month 8. Anticipating approximately 25% dropout, we plan to enroll 
120 participants. An effect size of similar magnitude has been reported previously in tele-
monitoring feedback from pharmacists in adult home BP monitoring trials (37). 
List of Abbreviations 
BP- blood pressure 
CKD- chronic kidney disease 
CV- cardiovascular 
SBP- systolic blood pressure 
ESKD- end-stage kidney disease 
SPRINT- Systolic Blood Pressure Intervention Trial  
eGFR- estimated glomerular filtration rate 
MDRD- Modification of Diet in Renal Disease   
RAAS- renin-angiotensin-aldosterone system 
AKI- acute kidney injury 
BMP- basic metabolic panel 
UPCR- urine protein creatinine ratio 
ABPM- ambulatory blood pressure monitoring  
DBP- diastolic blood pressure 
MAP- mean arterial pressure 
ARB- angiotensin receptor blockers  
ACE- angiotensin-converting enzyme 
 
This protocol has been published:   

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Se Ri Bae, Charles E McCulloch, Raymond K Hsu & Elaine Ku (2021) Intensive Home Blood 
Pressure Lowering in Advanced Chronic Kidney Disease: A Pilot Randomized Controlled Trial 
Protocol, Open Access Journal of Clinical Trials, , 21-29, DOI: 10.2147/OA JCT.S311821