Blood Pressure Lowering in Dialysis (BOLD) Trial

NCT03459807 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 16-20963R21DK114213
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (4)

• 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]

  1. Postdialysis unit systolic BP \<90 mmHg 2. Postdialysis unit systolic BP \>200 mmHg 3. Cramping during dialysis 4. Syncope episodes 5. Episodes of fall 6. Episodes of flash pulmonary edema 7. 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

Study Arms (2)

Home systolic blood pressure (SBP) <140 mmHg

EXPERIMENTAL

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; Procedure: Dry Weight Adjustment

Pre-dialysis SBP <140 mmHg

ACTIVE COMPARATOR

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; Procedure: Dry Weight Adjustment

Interventions

Anti-Hypertensive medications DRUG

Use of standard Anti-Hypertensive medications

Also known as: anti-hypertensive

Home systolic blood pressure (SBP) <140 mmHg; Pre-dialysis SBP <140 mmHg

Dry Weight Adjustment PROCEDURE

The participant's target post-dialysis dry weight is adjusted

Home systolic blood pressure (SBP) <140 mmHg; Pre-dialysis SBP <140 mmHg

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of Washington: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

UCSF

San Francisco, California, 94143, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

Related Publications (19)

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• SPRINT Research Group; Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC Jr, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015 Nov 26;373(22):2103-16. doi: 10.1056/NEJMoa1511939. Epub 2015 Nov 9.

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• Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol. 1998 Dec;9(12 Suppl):S16-23.

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  PMID: 11675417 BACKGROUND

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  PMID: 27226131 BACKGROUND

• Kalantar-Zadeh K, Block G, Humphreys MH, Kopple JD. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int. 2003 Mar;63(3):793-808. doi: 10.1046/j.1523-1755.2003.00803.x.

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• Port FK, Hulbert-Shearon TE, Wolfe RA, Bloembergen WE, Golper TA, Agodoa LY, Young EW. Predialysis blood pressure and mortality risk in a national sample of maintenance hemodialysis patients. Am J Kidney Dis. 1999 Mar;33(3):507-17. doi: 10.1016/s0272-6386(99)70188-5.

  PMID: 10070915 BACKGROUND

• Bansal N, Glidden DV, Mehrotra R, Townsend RR, Cohen J, Linke L, Palad F, Larson H, Hsu CY. Treating Home Versus Predialysis Blood Pressure Among In-Center Hemodialysis Patients: A Pilot Randomized Trial. Am J Kidney Dis. 2021 Jan;77(1):12-22. doi: 10.1053/j.ajkd.2020.06.014. Epub 2020 Aug 13.

  PMID: 32800842 RESULT

MeSH Terms

Conditions

Disease; Renal Insufficiency, Chronic

Interventions

Antihypertensive Agents

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes

Intervention Hierarchy (Ancestors)

Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Dr. Chi-yuan Hsu
• Organization: University of California, San Francisco

chi-yuan.hsu@ucsf.edu

415-476-2172

Study Officials

• Chi-yuan Hsu, MD

  Professor

  PRINCIPAL INVESTIGATOR

• Nisha Bansal, MD, MAS

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2018
• First Posted: March 9, 2018
• Study Start: March 23, 2018
• Primary Completion: December 6, 2018
• Study Completion: December 6, 2018
• Last Updated: July 3, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)