Blood Pressure Lowering in Dialysis (BOLD) Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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BOLD: A Trial of Blood Pressure Lowering in Dialysis

Conditions
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Blood Pressure, End Stage Renal Disease on Dialysis (Diagnosis), Chronic Kidney Diseases, Chronic Kidney Disease Stage 5

Intervention / Treatment
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* Drug: Anti-Hypertensive medications
* Procedure: Dry Weight Adjustment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form Undergoing in-center, thrice weekly hemodialysis for treatment of end-stage-renal-disease Greater than 3 months since initiation of dialysis Age 18 years or above Able to obtain a brachial blood pressure at dialysis and at home Exclusion Criteria: 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 Incarceration or institutionalized living which may prohibit measurement of home blood pressure Participation in another intervention study that may affect blood pressure Patients in whom systolic blood pressure is not measurable (e.g. those with left ventricular assist devices) Hypotension: average pre-dialysis systolic blood pressure <100 mmHg over last 2 weeks prior to screening while not taking any blood pressure medications Life expectancy <4 months Anticipated living donor kidney transplant within 4 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Home systolic blood pressure (SBP) <140 mmHg<br>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. | Drug: Anti-Hypertensive medications<br>* Use of standard Anti-Hypertensive medications<br>* Other names: anti-hypertensive;Procedure: Dry Weight Adjustment<br>* The participant's target post-dialysis dry weight is adjusted<br>|
| Active Comparator: Pre-dialysis SBP <140 mmHg<br>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. | Drug: Anti-Hypertensive medications<br>* Use of standard Anti-Hypertensive medications<br>* Other names: anti-hypertensive;Procedure: Dry Weight Adjustment<br>* The participant's target post-dialysis dry weight is adjusted<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility - Screen:Enrollment Ratio | Percentage of eligible participants screened and eventually enrolled in the study | Screening | 
| Adherence to Assigned Treatment Arm | Percentage of participants in the home blood pressure (BP) arm who are able to measure home BP and transmit readings to the research team. Overall, across 16 wks. | 4 months | 
| Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] | Postdialysis unit systolic BP <90 mmHg Postdialysis unit systolic BP >200 mmHg Cramping during dialysis Syncope episodes Episodes of fall Episodes of flash pulmonary edema Symptoms of dizziness | Assessed every 2 weeks over 4 months | 
| Mean Duration (in Minutes) of Recovery From Dialysis Treatments | Data were reported at study visits every 2 wks, the mean was calculated from the first to the last follow-up visit. The mean was calculated for each participant, then the overall mean was calculated for each arm. | Assessed every 2 weeks; Data averaged over 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood pressure, Hemodialysis, End-stage-renal-disease, Chronic kidney disease