Clinical trial NCT01421771: Blood Pressure in Dialysis Patients
Official title: Blood Pressure in Dialysis Patients (BID Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Renal Failure Chronic Requiring Hemodialysis
Blood Pressure
Dialysis
Lead sponsor: University of New Mexico
Sponsor class: OTHER
Collaborators: name: Tufts Medical Center
name: Medical University of South Carolina
name: University of Pittsburgh Medical Center
name: The Cleveland Clinic
name: Case Western Reserve University
First posted: 2011-08-23
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Hypertension is a major cause of cardiovascular (CV) morbidity and mortality. Although studies in the general population have demonstrated a continuous reduction in CV risk with each mmHg drop in systolic blood pressure (SBP), multiple observational studies conducted in hemodialysis (HD) patients have demonstrated that patients with mild to moderate hypertension may have decreased mortality compared to those with normal blood pressure (BP). The investigators recently reported that among HD patients, those with routine pre-dialysis BP values that met the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines (\<140/90 mm Hg) had increased mortality compared to patients with mild to moderate hypertension. However, these observational studies included untreated patients in whom low or normal BP may reflect significant cardiac disease or other comorbid conditions. In the setting of reduced vascular compliance and impaired autoregulation, aggressive BP lowering may decrease coronary or cerebral perfusion. Thus, it is unclear if aggressive BP lowering will be harmful or beneficial. A well-designed randomized control trial (RCT) is needed to answer this important question. Prior to conducting a full-scale RCT it is prudent to conduct a pilot study to assess feasibility and inform the design of the former. The investigators propose to conduct a pilot RCT in a prevalent cohort of HD patients to assess the safety and feasibility of treating patients to a low (110-140 mmHg)and standard (155-165) mm Hg pre-dialysis BP target.

Detailed description: Mortality and morbidity among hemodialysis (HD) patients remain unacceptably high, thus there is a compelling need to improve clinical outcomes. Accordingly, the National Kidney Foundation's Kidney Disease Outcome Quality Improvement program (KDOQI) has published a guideline calling for a pre-dialysis systolic blood pressure (SBP) \<140 mmHg in HD patients. However, the evidence supporting this guideline was graded as weak since it was largely extrapolated from the general population. Studies in the general population have demonstrated a continuous reduction in cardiovascular risk with each mmHg drop in systolic blood pressure (SBP), extending below levels that were in past considered "normal". The Systolic Blood Pressure Intervention Trial (SPRINT) study has showed a decrease in the composite outcome of CV events and CV mortality among non-diabetic patients at high risk for cardiovascular events by targeting a SBP of \<120 mmHg. It is reasonable to postulate that intensive control of BP may be beneficial in HD patients, who in many ways resemble patients in SPRINT except that they have progressed to end stage renal disease. Thus, it is timely to propose conducting a RCT of intensive versus standard control of blood pressure in HD patients.

The investigators recognize that from observational studies suggest that mortality among HD patients may be increased among patients who meet the current KDOQI guideline. Unidentified confounders may have contributed to these surprising findings. The conclusions reached by observational studies in HD patients have often been refuted by randomized controlled trials (RCTs). Therefore, a RCT is needed to determine if a pre-dialysis SBP \<140 mmHg specified by KDOQI is an appropriate target. Prior to beginning a full-scale-RCT, it is imperative to conduct a pilot study to demonstrate safety and efficacy and to inform the design of the full-scale study. The pilot study is designed to answer the following questions:

1. What are the estimated recruitment, accrual and retention rates?
2. What proportions of patients in each arm will achieve and maintain SBP within the assigned target and will the investigators achieve equal or greater than 10mmHg separation in the average SBP between the two arms?
3. What are the anticipated adverse and serious adverse events rates within the intensive and standard arms?
4. What end points should be used in the full-scale trial?
5. What blood pressure (BP) measurements e.g., routine dialysis unit BP (RDUBPM), standardized dialysis unit BP (SDUBPM), standardized home BP (HBPM) or ambulatory BP monitoring (ABPM) to guide therapy? Although SDUBPM, HBPM and ABPM may be more powerful than RDUBP in predicting clinical outcomes,long term adherence with these techniques has not been demonstrated.

Specific Aims

1. Establish procedures for SDUBPM, HBPM and ABPM and web-based data entry.
2. Recruit and randomize patients into two treatment arms with target pre-dialysis SDUSBPM values \<140 and \< 160 mmHg and measure recruitment, accrual, and dropout rates in each arm.
3. Assess the feasibility of attaining and maintaining these targets and the degree of SBP separation achieved during a one year intervention.
4. Measure adherence rates for obtaining protocol SDUBPM, HBPM and ABPM over the one-year intervention.
5. Assess the safety of treating participants to the study's SBP targets by measuring occurrence rates of CVD and non-CVD morbidity and mortality and other adverse and serious adverse events in each arm.
6. Compare the differences in changes in left ventricular mass index (LVMI), aortic pulse wave velocity(APWV), and aortic distensibility, respectively, between the two study arms.
7. Conduct statistical analyses to inform the design of the full-scale study.

Eligibility criteria: Inclusion Criteria

1. Age ≥ 18 years
2. On thrice weekly maintenance hemodialysis for greater than 90 days
3. For entry into baseline period: 2-week average RDUSBPM \> 155 mm Hg on AHT medications or \< 155 mm Hg on ≥ 1 AHT medications For randomization: 2-week average SDUSBPM ≥ 155 mm Hg

Exclusion Criteria:

1. Two- week average, pre-dialysis mid-week SDUSBPM ≥180 mmHg on maximal doses of ≥ 4 antihypertensive agents;
2. Inability to measure blood pressures in an upper arm;
3. History of inter or post-dialytic hypotension (defined as systolic blood pressure \<90 mmHg) within the past 2 weeks or inter- or post- dialytic hypotension requiring hospitalization (including emergency room visit) and/or the use of midodrine in the past 6 months;
4. Required one or more urgent, unscheduled dialysis treatment for congestive heart failure in the past 3 months (other than in an incident patient at the time of starting dialysis);
5. Acute myocardial infarction, unstable angina or stroke/ TIA in past three the 3 months;
6. Severe aortic valve stenosis (valve area \<1cm 2) carotid artery stenosis (\>70% stenosis);
7. Known abdominal aortic aneurysm \>5 cm in diameter or thoracic aortic aneurysm of any diameter;
8. Body mass index \>40 kg/m2 or arm circumference \> 52 cm, which precludes measuring blood pressure with the "thigh" blood pressure cuff;
9. Life expectancy \<1 year;
10. A living donor, kidney transplant, or switch to peritoneal dialysis scheduled within the next year;
11. Significant cognitive impairment;
12. spKt/V ≤1.2 in the past 2 months;
13. Active liver disease;
14. Active alcohol or substance abuse including narcotics within the past year;
15. Contraindication to cardiac MRI;
16. Current or planned pregnancy within the next year;
17. Unwillingness to consent to pregnancy test and/or use of birth control if of childbearing potential;
18. Suspicion that the participant will not be willing or able to adhere to prescribed medications and study protocol;
19. Incarcerated;
20. Significant concern about the study expressed by spouse, significant other, family member primary nephrologist or primary care physician;
21. Participation in another intervention study;
22. Unable to speak or understand English or Spanish;
23. Plan to relocate within one year;
24. participation in another intervention study .

Primary outcomes:
measure: Number of Participants Assessed for Intensive (110-140 mm Hg) and Standard (155-165mm Hg) Pre-dialysis Standardized BP Goal
timeFrame: one year
Secondary outcomes:
measure: Number or Participants Assessed for Change in LV Mass
timeFrame: One year
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dialysis Clinic Inc - Boston
state: Massachusetts
city: Boston
country: United States
facility: DaVita Boston
state: Massachusetts
city: Concord
country: United States
facility: Dialysis Clinic Inc - Walden Pond Clinic
state: Massachusetts
city: Jamaica Plain
country: United States
facility: Dialysis Clinic Inc - Faulkner
state: Massachusetts
city: Somerville
country: United States
facility: Dialysis Clinic Inc - Somerville
state: Massachusetts
city: Albuquerque
country: United States
facility: Dialysis Clinic Inc - Albuquerque
state: New Mexico
city: Albuquerque
country: United States
facility: Dialysis Clinic Inc - Albuquerque South
state: New Mexico
city: Albuquerque
country: United States
facility: Dialysis Clinic Inc - Albuquerque East
state: New Mexico
city: Grants
country: United States
facility: Dialysis Clinic Inc - Grants
state: New Mexico
city: Rio Rancho
country: United States
facility: Dialysis Clinic Inc - Rio Rancho
state: New Mexico
city: Cleveland
country: United States
facility: Centers for Dialysis Care East
state: Ohio
city: Cleveland
country: United States
facility: Centers for Dialysis Care - Shaker Heights
state: Ohio
city: Pittsburgh
country: United States
facility: Dialysis Clinic Inc - Oakland
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Dialysis Clinic Inc - Banksville
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Dialysis Clinic Inc - Point Breeze
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Dialysis Clinic Inc - North Hills
state: Pennsylvania
city: Charleston
country: United States
facility: Dialysis Clinic Inc - Magnolia Court
state: South Carolina
city: Charleston
country: United States
facility: Dialysis Clinic Inc - West Ashley
state: South Carolina
city: Charleston
country: United States
facility: Dialysis Clinic Inc - James Island
state: South Carolina
city: Mount Pleasant
country: United States
facility: Dialysis Clinic Inc - East Cooper
state: South Carolina
city: North Charleston
country: United States
facility: Dialysis Clinic Inc - Azalea Place
state: South Carolina
Study officials:
affiliation: University New Mexico
name: Philip Zager, MD
role: STUDY_CHAIR
affiliation: Tufts Medical Center
name: Dana Miskulin, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Jennifer Gassman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: David Ploth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh
name: Manisha Jhamb
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University
name: Mahboob Rahman
role: PRINCIPAL_INVESTIGATOR
References:
citation: Miskulin DC, Gassman J, Schrader R, Gul A, Jhamb M, Ploth DW, Negrea L, Kwong RY, Levey AS, Singh AK, Harford A, Paine S, Kendrick C, Rahman M, Zager P. BP in Dialysis: Results of a Pilot Study. J Am Soc Nephrol. 2018 Jan;29(1):307-316. doi: 10.1681/ASN.2017020135. Epub 2017 Dec 6.