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CompletedNCT03459807BOLDUpdated Jul 3, 2023Results posted

Blood Pressure Lowering in Dialysis (BOLD) Trial

A Phase 2 interventional study of Anti-Hypertensive medications and Dry Weight Adjustment in Blood Pressure, End Stage Renal Disease on Dialysis (Diagnosis) and Chronic Kidney Diseases, sponsored by University of California, San Francisco. Completed at 2 sites in United States. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2023-07-03.

Sponsored by University of California, San Francisco · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
50
Allocation
Randomized
Ages
18 Years to 100 Years
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • 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
03

Who can participate

Ages eligible
18 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No

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. Age 18 years or above
  5. Able to obtain a brachial blood pressure at dialysis and at home

Exclusion criteria

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
50 participants (actual)

Study arms

  • Experimental
    Home systolic blood pressure (SBP) <140 mmHg

    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

  • Active comparator
    Pre-dialysis SBP <140 mmHg

    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

  • DrugAnti-Hypertensive medications

    Use of standard Anti-Hypertensive medications

    Also known as: anti-hypertensive

  • ProcedureDry Weight Adjustment

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

05

What researchers measure

Primary outcomes

  1. Feasibility - Screen:Enrollment Ratio

    Percentage of eligible participants screened and eventually enrolled in the study

    Time frame: Screening

  2. 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.

    Time frame: 4 months

  3. 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

    Time frame: Assessed every 2 weeks over 4 months

  4. 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.

    Time frame: Assessed every 2 weeks; Data averaged over 16 weeks

06

Results

Posted Jul 3, 2023

Participant flow

Participant flow — Overall Study
MilestoneHome Systolic Blood Pressure (SBP) <140 mmHgPre-dialysis SBP <140 mmHg
Started2525
Completed2524
Not completed01
Withdrew: Withdrawal due to transplant01

Outcome measures

PrimaryFeasibility - Screen:Enrollment Ratio

Percentage of eligible participants screened and eventually enrolled in the study

Time frame:
Screening
Reported as:
Count of participants · Participants
Feasibility - Screen:Enrollment Ratio
ParticipantsParticipants Screened
Feasibility - Screen:Enrollment Ratio50
PrimaryAdherence 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.

Time frame:
4 months
Reported as:
Number · percentage of participants
Adherence to Assigned Treatment Arm
percentage of participantsHome Systolic Blood Pressure (SBP) <140 mmHg
0 BP Readings3
1 BP Reading4
2 BP Readings93
PrimaryNumber 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

Time frame:
Assessed every 2 weeks over 4 months
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]
ParticipantsHome Systolic Blood Pressure (SBP) <140 mmHgPre-dialysis SBP <140 mmHg
Postdialysis unit systolic BP <90 mmHg20
Postdialysis unit systolic BP >200 mmHg32
Cramping during dialysis1318
Syncope episodes11
Episodes of fall36
Episodes of flash pulmonary edema00
Symptoms of dizziness1014
PrimaryMean 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.

Time frame:
Assessed every 2 weeks; Data averaged over 16 weeks
Reported as:
Mean · Minutes
Mean Duration (in Minutes) of Recovery From Dialysis Treatments
MinutesHome Systolic Blood Pressure (SBP) <140 mmHgPre-dialysis SBP <140 mmHg
Mean Duration (in Minutes) of Recovery From Dialysis Treatments327 ± 42268 ± 37

Adverse events

Collected over 16 weeks. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Home Systolic Blood Pressure (SBP) <140 mmHg0/25 (0%)2/25 (8%)25/25 (100%)
Dialysis SBP <140 mmHg0/25 (0%)1/25 (4%)25/25 (100%)
Most frequent serious events
Most frequent serious events
EventHome Systolic Blood Pressure (SBP) <140 mmHgDialysis SBP <140 mmHg
SyncopeCardiac disorders2/251/25
Most frequent other events
Most frequent other events
EventHome Systolic Blood Pressure (SBP) <140 mmHgDialysis SBP <140 mmHg
Intradialytic hypotensionCardiac disorders21/2518/25
CrampingMusculoskeletal and connective tissue disorders13/2518/25
Symptoms of fatigueGeneral disorders15/2516/25
Symptoms of dizzinessGeneral disorders10/2514/25
Symptoms of lightheadednessGeneral disorders14/2512/25
FallGeneral disorders3/256/25
Predialysis SBP > 200 mm HgCardiac disorders4/254/25
Postdialysis SBP > 200 mm HgCardiac disorders3/252/25
Predialysis SBP < 90 mm HgCardiac disorders1/252/25
Postdialysis SBP < 90 mm HgCardiac disorders2/250/25

Baseline characteristics

Age, Continuous
Age, Continuous(years)Home Systolic Blood Pressure (SBP) <140 mmHgPre-dialysis SBP <140 mmHgTotal
Mean56.4 ± 13.156.9 ± 14.456.6 ± 13.6
Sex: Female, Male
Sex: Female, Male(Participants)Home Systolic Blood Pressure (SBP) <140 mmHgPre-dialysis SBP <140 mmHgTotal
Female12820
Male131730
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Home Systolic Blood Pressure (SBP) <140 mmHgPre-dialysis SBP <140 mmHgTotal
American Indian or Alaska Native000
Asian6511
Native Hawaiian or Other Pacific Islander123
Black or African American11920
White6814
More than one race000
Unknown or Not Reported112
Region of Enrollment
Region of Enrollment(participants)Home Systolic Blood Pressure (SBP) <140 mmHgPre-dialysis SBP <140 mmHgTotal
United States252550
07

Study locations

2 sites
  • UCSF
    San Francisco, California 94143, United States
  • University of Washington
    Seattle, Washington 98104, United States
08

References and documents

Publications

  • Lewington S, Clarke R, Qizilbash N, Peto R, Collins R; Prospective Studies Collaboration. 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 Dec 14;360(9349):1903-13. doi: 10.1016/s0140-6736(02)11911-8. Erratum In: Lancet. 2003 Mar 22;361(9362):1060. PubMed 12493255 ↗
  • Flack JM, Neaton J, Grimm R Jr, Shih J, Cutler J, Ensrud K, MacMahon S. Blood pressure and mortality among men with prior myocardial infarction. Multiple Risk Factor Intervention Trial Research Group. Circulation. 1995 Nov 1;92(9):2437-45. doi: 10.1161/01.cir.92.9.2437. PubMed 7586343 ↗
  • MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, Abbott R, Godwin J, Dyer A, Stamler J. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990 Mar 31;335(8692):765-74. doi: 10.1016/0140-6736(90)90878-9. PubMed 1969518 ↗
  • Vamos EP, Harris M, Millett C, Pape UJ, Khunti K, Curcin V, Molokhia M, Majeed A. Association of systolic and diastolic blood pressure and all cause mortality in people with newly diagnosed type 2 diabetes: retrospective cohort study. BMJ. 2012 Aug 30;345:e5567. doi: 10.1136/bmj.e5567. PubMed 22936794 ↗
  • James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, Smith SC Jr, Svetkey LP, Taler SJ, Townsend RR, Wright JT Jr, Narva AS, Ortiz E. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014 Feb 5;311(5):507-20. doi: 10.1001/jama.2013.284427. Erratum In: JAMA. 2014 May 7;311(17):1809. PubMed 24352797 ↗
  • 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. Erratum In: N Engl J Med. 2017 Dec 21;377(25):2506. doi: 10.1056/NEJMx170008. PubMed 26551272 ↗
  • Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, McCullough PA, Kasiske BL, Kelepouris E, Klag MJ, Parfrey P, Pfeffer M, Raij L, Spinosa DJ, Wilson PW; American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention. Hypertension. 2003 Nov;42(5):1050-65. doi: 10.1161/01.HYP.0000102971.85504.7c. No abstract available. PubMed 14604997 ↗
  • 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. PubMed 11443763 ↗
  • Locatelli F, Marcelli D, Conte F, D'Amico M, Vecchio LD, Limido A, Malberti F, Spotti D. Survival and development of cardiovascular disease by modality of treatment in patients with end-stage renal disease. J Am Soc Nephrol. 2001 Nov;12(11):2411-2417. doi: 10.1681/ASN.V12112411. PubMed 11675417 ↗
  • Ok E, Asci G, Chazot C, Ozkahya M, Mees EJ. Controversies and problems of volume control and hypertension in haemodialysis. Lancet. 2016 Jul 16;388(10041):285-93. doi: 10.1016/S0140-6736(16)30389-0. Epub 2016 May 22. PubMed 27226131 ↗
  • 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. PubMed 12631061 ↗
  • Duranti E, Imperiali P, Sasdelli M. Is hypertension a mortality risk factor in dialysis? Kidney Int Suppl. 1996 Jun;55:S173-4. PubMed 8743547 ↗
  • Zager PG, Nikolic J, Brown RH, Campbell MA, Hunt WC, Peterson D, Van Stone J, Levey A, Meyer KB, Klag MJ, Johnson HK, Clark E, Sadler JH, Teredesai P. "U" curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc. Kidney Int. 1998 Aug;54(2):561-9. doi: 10.1046/j.1523-1755.1998.00005.x. Erratum In: Kidney Int 1998 Oct;54(4):1417. PubMed 9690224 ↗
  • Cheung AK, Sarnak MJ, Yan G, Dwyer JT, Heyka RJ, Rocco MV, Teehan BP, Levey AS. Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients. Kidney Int. 2000 Jul;58(1):353-62. doi: 10.1046/j.1523-1755.2000.00173.x. PubMed 10886582 ↗
  • Agarwal R. Blood pressure and mortality among hemodialysis patients. Hypertension. 2010 Mar;55(3):762-8. doi: 10.1161/HYPERTENSIONAHA.109.144899. Epub 2010 Jan 18. PubMed 20083728 ↗
  • Kovesdy CP, Bleyer AJ, Molnar MZ, Ma JZ, Sim JJ, Cushman WC, Quarles LD, Kalantar-Zadeh K. Blood pressure and mortality in U.S. veterans with chronic kidney disease: a cohort study. Ann Intern Med. 2013 Aug 20;159(4):233-42. doi: 10.7326/0003-4819-159-4-201308200-00004. PubMed 24026256 ↗
  • Robinson BM, Tong L, Zhang J, Wolfe RA, Goodkin DA, Greenwood RN, Kerr PG, Morgenstern H, Li Y, Pisoni RL, Saran R, Tentori F, Akizawa T, Fukuhara S, Port FK. Blood pressure levels and mortality risk among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Kidney Int. 2012 Sep;82(5):570-80. doi: 10.1038/ki.2012.136. Epub 2012 Jun 20. PubMed 22718187 ↗
  • 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. PubMed 10070915 ↗
  • 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. PubMed 32800842 ↗

Study documents

  • Protocol and statistical analysis plan · Feb 5, 2018
  • Informed consent form · Jun 27, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03459807
Lead sponsor
University of California, San Francisco
Collaborators
University of Washington, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Responsible party
Sponsor
First posted
Mar 9, 2018
Start date
Mar 23, 2018
Primary completion
Dec 6, 2018
Completion
Dec 6, 2018
Results posted
Jul 3, 2023
Last update
Jul 3, 2023

Study contacts

Chi-yuan Hsu, MD
principal investigator · Professor
Nisha Bansal, MD, MAS
principal investigator · University of Washington

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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