Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01421771 |
| Other study ID # |
1R01DK083424-01A1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 2011 |
| Est. completion date |
June 2016 |
Study information
| Verified date |
November 2023 |
| Source |
University of New Mexico |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
