Blood Pressure Lowering in Dialysis (BOLD) Trial

Blood Pressure Clinical Trial

— BOLD  

Official title:

BOLD: A Trial of Blood Pressure Lowering in Dialysis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03459807
• Other study ID #: 16-20963
• Secondary ID: R21DK114213
• Status: Completed
• Phase: Phase 2
• Start date: March 23, 2018
• Est. completion date: December 6, 2018

Study information

• Verified date: June 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: December 6, 2018
• Est. primary completion date: December 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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:

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Anti-Hypertensive medications
Use of standard Anti-Hypertensive medications

Procedure:
• Dry Weight Adjustment
The participant's target post-dialysis dry weight is adjusted

Locations

Country	Name	City	State
United States	UCSF	San Francisco	California
United States	University of Washington	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), University of Washington

Country where clinical trial is conducted

United States, 

References & Publications (19)

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. — View Citation

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: 10.105 — View Citation

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. — View Citation

Duranti E, Imperiali P, Sasdelli M. Is hypertension a mortality risk factor in dialysis? Kidney Int Suppl. 1996 Jun;55:S173-4. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility - Screen:Enrollment Ratio	Percentage of eligible participants screened and eventually enrolled in the study	Screening
Primary	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
Primary	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
Primary	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