Mechanism of Increased Ambulatory Blood Pressure in Patients With Intradialytic Hypertension and Hemodialysis Controls: A Case Control Study and Crossover Trial Comparing Carvedilol and Prazosin Hydrochloride

Study ID
STU 052012-029

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Tiara Tyler
214-645-8240
tiara.tyler@utsouthwestern.edu

Principal Investigator
Peter Van Buren

Summary

The broad aim of this study is to investigate how extracellular volume and vascular resistance affect blood pressure in patients with intradialytic hypertension and hemodialysis controls.
aims 1 and 2, a case control study will be conducted in a total of 249 subjects: 83 subjects with intradialytic hypertension 83 hemodialysis control subjects whose blood pressure decreases during screening (Control a), and 83 subjects who are hypertensive hemodialysis patients whose blood pattern during screening does not fit that of either case subjects or control a (control B). The subjects with intradialytic hypertension will be identified as hypertensive hemodialysis patients (systolic blood pressure greater than or equal to 140 mmHg pre-hemodialysis or greater than or equal to 130 mmHg post-dialysis during screening) with an increase in systolic blood pressure from pre to post-hemodialysis at least 10 mmHg in at least 4/6 screening treatments. The hemodialysis control a subjects will be hypertensive hemodialysis patients whose blood pressure decreases at least 10 mmHg from pre to post-hemodialysis during screening. The hemodialysis control B subjects will be hypertensive hemodialysis patients whose blood pressure does not necessarily increase or decrease by 10 mmHg in 4/6 hemodialysis treatments. The primary outcome in specific aim 1 will be the ratio of extracellular water to total body water measured post-hemodialysis. This will be compared between groups (case and Control a; case and Control B). The primary outcome variable for Specific aim 2 will be the hourly blood pressure slope during the 44-hour interdialytic time period.
a subset of case subjects with intradialytic hypertension (n[?]25) will participate in a crossover study. all subjects in aim three will receive carvedilol for 8 weeks and prazosin hydrochloride for 8 weeks. Subjects will be randomized to receive either carvedilol or prazosin hydrochloride first in a 1:1 ratio using a computerized random number generator. Following 8 weeks on the first study drug, all subjects will undergo a 2 week washout period prior to starting the other study drug. The primary outcome of this aim is the change in endothelin-1 from pre to post hemodialysis.

Participant Eligibility

Aims 1 and 2:
1. Hemodialysis patients from any of 3 UT-Southwestern affiliated hemodialysis units
2. Age 18-80 years of age
3. Hypertension, defined as a pre-hemodialysis systolic blood pressure greater than or equal to 140 mmHg, or a post-hemodialysis systolic blood pressure greater than or equal to 130 mmHg.
4. For case subjects: systolic blood pressure increases >=10 mmHg from pre to post-hemodialysis in >=4/6 screening treatments.
5. For control A subjects: systolic blood pressure decreases >=10 mmHg from pre to post-hemodialysis in >=4/6 screening treatments. Control subjects will be selected to balance out the distribution of case subjects among age groups (by decade), presence of diabetes, and gender.
6. For control B subjects: systolic blood pressure does not increase or decrease > 10 mmHg in 4/6 screening treatments.

Aim 3:
1. See inclusion criteria for case subjects in Aims 1 and 2. All case subjects enrolled in the study will be consecutively screened for eligibility for Aim 3 (see exclusion criteria below) until the target population for Aim 3 is reached.