| Conditions: |
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Hypertension - Renal Failure Chronic Requiring Hemodialysis - Fluid Overload |
| Purpose: |
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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.
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| Study Summary: |
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Mortality and morbidity among hemodialysis (HD) patients remain unacceptably high, thus
there is a compelling need to improve clinical outcomes. Since minorities are
overrepresented in the HD population, accomplishing this goal will improve the health of
medically underserved minorities. 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". In light of these studies NIH
is funding ACCORD and SPRINT which are designed to compare the impact of intensive (SBP< 120
mmHg) and standard (SBP<160 mmHg) control of hypertension among patients with type 2
diabetes mellitus and chronic kidney disease, respectively. It is reasonable to postulate
that intensive control of BP may be beneficial in HD patients, who in many ways resemble
patients in ACCORD and 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, which would incorporate many of the design features of Action to
Control cardiovascular Risk in Diabetes (ACCORD) and Systolic Blood Pressure Intervention
Trial (SPRINT).
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.
Outcomes in the Pilot Study: The primary outcome is the feasibility and safety of attaining
and maintaining the assigned SBP targets over a planned one year intervention. Secondary
outcomes include differences in the rates of change in left ventricular mass (LVM) and
health related quality of life (HRQOL) between the two groups.
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.
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| Criteria: |
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Inclusion Criteria
1. Age ≥ 18 years
2. On thrice weekly maintenance hemodialysis for greater than 90 days
3. Two-week average pre-dialysis RDUSYS BPM >=155 mm Hg or if less than 155 on
antihypertensive medications as follows: at least 1 med for RDUSYS BPM 150-154, 2
meds for RDUSYS BPM 145-149; 3 meds for RDUSYS BPM 140-144. Patient and physician
must agree to backtitrate medications if RDU SYS BPM <155.
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 .
During the screening pre-randomization phase, eligibility of potential subjects will be
documented and evaluated using information in the On-Line Randomization Screen. Patients
will be instructed in study design, objectives, and procedures, after which informed
consent will be obtained. The study coordinator and site investigator should review this
pre-randomization data with attention to judging the patient's ability to adhere to study
protocols. A maximum of 12-weeks will be allowed between the screening visit and
randomization. If over 12-weeks have elapsed, then potential subjects will need to be
re-screened. Eligible participants will be instructed to bring their medications to the
baseline visit.
The site PI and/or study coordinator will rescreen patients who appear to meet the study
entry criteria using the Blood Pressure in Hemodialysis Pilot Study Eligibility Checking
Form. The Blood Pressure in Hemodialysis Pilot Study Screening Physical Exam and Study
Questionnaire Form will be completed for potential subjects who provide informed consent
to assess eligibility for the study. For women of childbearing potential, a urine
pregnancy test will be done at a local lab and the results documented on this form.
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| NCT ID: |
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NCT01421771 |
| Primary Contact: |
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Study Chair
Philip Zager, MD
University New Mexico
Dana Miskulin, MD, MS
Phone: 617 636 9936
Email: dmiskulin@tuftsmedicalcenter.org
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| Backup Contact: |
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Email: pzag@unm.edu
Philip Zager, MD
Phone: 505-247-4044
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| Location Contact: |
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Boston, Massachusetts 02118
United States
Dana Miskulin, MD
Phone: 617-636-9936
Email: dmiskulin@tuftsmedicalcenter.org
Site Status: Recruiting |