Clinical trial NCT01421771
Conditions: Hypertension Renal Failure Chronic Requiring Hemodialysis Blood Pressure Dialysis
Sponsor: University of New Mexico
Start date: 2011-10-01; Completion date: 2016-06-01
Enrollment: 126 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: Treatment to a pre-dialysis standardized dialysis unit systolic blood pressure of 110-140 mm Hg arm 2: Treatment to a pre-dialysis Standardized dialysis unit systolic BP of 155-165 mm Hg
Interventions: intervention 1: Antihypertensive Agents intervention 2: Dry weight Challenge intervention 3: Extend dialysis treatment time and re-challenge estimated dry weight
Intervention descriptions: intervention 1: 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 intervention 2: 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 intervention 3: Extend dialysis treatment time and re-challenge estimated dry weight

Protocol documents: