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Blood Pressure in Dialysis Patients (BID)

This study has been completed.
Sponsor:
Collaborators:
Tufts Medical Center
Medical University of South Carolina
University of Pittsburgh
The Cleveland Clinic
Case Western Reserve University
Information provided by (Responsible Party):
University of New Mexico
ClinicalTrials.gov Identifier:
NCT01421771
First received: August 16, 2011
Last updated: October 4, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention
Hypertension
Renal Failure Chronic Requiring Hemodialysis
Blood Pressure
Dialysis
Drug: Antihypertensive Agents
Other: Dry weight Challenge
Dietary Supplement: Extend dialysis treatment time and re-challenge estimated dry weight

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Blood Pressure in Dialysis Patients (BID Study)

Further study details as provided by University of New Mexico:

Primary Outcome Measures:
  • Feasibility and safety of randomizing patients to an intensive (110-140 mm Hg) and standard (155-165mm Hg)pre-dialysis standardized BP Goal [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    To assess the safety and feasibility of randomizing patients to each of the BP arms To assess rates of intradialytic hypotension requiring intervention, SAEs, hospitalizations, CV-related hospitalizations between treatment arms


Secondary Outcome Measures:
  • Change in LV mass [ Time Frame: One year ] [ Designated as safety issue: No ]
    LV mass will be measured by MRI at baseline and one year after randomization

  • Adverse events, serious adverse events, major CVD events and mortality [ Time Frame: One year ] [ Designated as safety issue: No ]
    Adverse events, serious adverse events, major CVD events and mortality will be evaluated over one year across study arms

  • Health-related quality of life [ Time Frame: One year ] [ Designated as safety issue: No ]
    HRQOL will be assessed using the SF-36, and the Fact fatigue scale and a validated question about dialysis recovery time at baseline and one year after randomization


Enrollment: 126
Study Start Date: July 2010
Study Completion Date: June 2016
Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment to an intensive BP goal
Treatment to a pre-dialysis standardized dialysis unit systolic blood pressure of 110-140 mm Hg
Drug: Antihypertensive Agents

Study formulary consists of ACE/ARB, Beta Adrenergic Blocker, Calcium Channel Blocker, vasodilators, peripheral alpha antagonist and central alpha agonist.

ACE I or ARB is first line, the order of addition of subsequent medications is per the discretion of the investigator

Other: Dry weight Challenge
Reduce the estimated dry weight of the patient's progressively over 2 -week intervals until the dry weight challenge is no longer tolerated or the patient is at BP goal
Dietary Supplement: Extend dialysis treatment time and re-challenge estimated dry weight
Extend dialysis treatment time and re-challenge estimated dry weight
Placebo Comparator: Treatment to standard BP goal
Treatment to a pre-dialysis Standardized dialysis unit systolic BP of 155-165 mm Hg
Drug: Antihypertensive Agents

Study formulary consists of ACE/ARB, Beta Adrenergic Blocker, Calcium Channel Blocker, vasodilators, peripheral alpha antagonist and central alpha agonist.

ACE I or ARB is first line, the order of addition of subsequent medications is per the discretion of the investigator

Other: Dry weight Challenge
Reduce the estimated dry weight of the patient's progressively over 2 -week intervals until the dry weight challenge is no longer tolerated or the patient is at BP goal
Dietary Supplement: Extend dialysis treatment time and re-challenge estimated dry weight
Extend dialysis treatment time and re-challenge estimated dry weight

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 .
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01421771

Locations
United States, Massachusetts
Dialysis Clinic Inc - Boston
Boston, Massachusetts, United States, 02111
DaVita Boston
Boston, Massachusetts, United States, 02118
Dialysis Clinic Inc - Walden Pond Clinic
Concord, Massachusetts, United States, 01742
Dialysis Clinic Inc - Faulkner
Jamaica Plain, Massachusetts, United States, 02130
Dialysis Clinic Inc - Somerville
Somerville, Massachusetts, United States, 02145
United States, New Mexico
Dialysis Clinic Inc - Albuquerque
Albuquerque, New Mexico, United States, 87102
Dialysis Clinic Inc - Albuquerque South
Albuquerque, New Mexico, United States, 87105
Dialysis Clinic Inc - Albuquerque East
Albuquerque, New Mexico, United States, 87110
Dialysis Clinic Inc - Grants
Grants, New Mexico, United States, 87020
Dialysis Clinic Inc - Rio Rancho
Rio Rancho, New Mexico, United States, 87124
United States, Ohio
Centers for Dialysis Care East
Cleveland, Ohio, United States, 44106
Centers for Dialysis Care - Shaker Heights
Cleveland, Ohio, United States, 44122
United States, Pennsylvania
Dialysis Clinic Inc - Oakland
Pittsburgh, Pennsylvania, United States, 15213
Dialysis Clinic Inc - Banksville
Pittsburgh, Pennsylvania, United States, 15216
Dialysis Clinic Inc - Point Breeze
Pittsburgh, Pennsylvania, United States, 15221
Dialysis Clinic Inc - North Hills
Pittsburgh, Pennsylvania, United States, 15237
United States, South Carolina
Dialysis Clinic Inc - Magnolia Court
Charleston, South Carolina, United States, 29403
Dialysis Clinic Inc - West Ashley
Charleston, South Carolina, United States, 29407
Dialysis Clinic Inc - James Island
Charleston, South Carolina, United States, 29412
Dialysis Clinic Inc - East Cooper
Mt. Pleasant, South Carolina, United States, 29464
Dialysis Clinic Inc - Azalea Place
North Charleston, South Carolina, United States, 29406
Sponsors and Collaborators
University of New Mexico
Tufts Medical Center
Medical University of South Carolina
University of Pittsburgh
The Cleveland Clinic
Case Western Reserve University
Investigators
Study Chair: Philip Zager, MD University New Mexico
Principal Investigator: Dana Miskulin, PhD Tufts Medical Center
Principal Investigator: Jennifer Gassman, MD The Cleveland Clinic
Principal Investigator: David Ploth, MD Medical University of South Carolina
Principal Investigator: Manisha Jhamb University of Pittsburgh
Principal Investigator: Mahboob Rahman Case Western Reserve University
  More Information

Responsible Party: University of New Mexico
ClinicalTrials.gov Identifier: NCT01421771     History of Changes
Other Study ID Numbers: 1R01DK083424-01A1 
Study First Received: August 16, 2011
Last Updated: October 4, 2016
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Failure, Chronic
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Antihypertensive Agents

ClinicalTrials.gov processed this record on December 02, 2016