Intradialytic Hypertension
Conditions
Keywords
Hypertension, Hemodialysis
Brief summary
1. To determine in a cross sectional case-controlled cohort study of 50 hemodialysis patients if blood pressure elevations with hemodialysis are associated with decreased endothelial cell function (measured by brachial artery flow mediated dilation and endothelial progenitor cell number), both of which are novel mechanistic markers in the causal pathway for detrimental cardiovascular outcomes; and 2. To determine if lowering blood pressure with carvedilol in 25 ESRD subjects with blood pressure elevations with hemodialysis can improve endothelial cell dysfunction as a surrogate mechanistic marker for improving cardiovascular outcomes.
Interventions
DRUGCarvedilol
Carvedilol 6.25 mg BID titrated weekly to maximum of 50 mg bid
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Texas Southwestern Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* on hemodialysis \> 30 days * aged 18 to 80 years old * ability to provide informed consent * Primary nephrologist deems patient is at target dry weight * Predialysis SBP \>140 or postdialysis SBP\>130
Exclusion criteria
* Patients with active wounds * Blood pressure unable to be measured by routine mechanisms in the upper extremity * Change in blood pressure medications in the previous 2 weeks * Intolerance of beta or alpha-blockers * pregnancy * Resting heart rate \<50 * Life expectancy \< 6 months * Current therapy with carvedilol or contraindication to carvedilol (ONLY in the intervention arm)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Endothelial Progenitor Cells | 12 weeks | 1. ALDH bright cells reported as percentage of mononuclear cells. These were assayed using flow cytometry 2. CD34/CD133 endothelial progenitor cells reported as percentage of mononuclear cells. These were assayed using flow cytometry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Flow Mediated Vasodilation | 12 weeks | Measured as percent change in brachial artery diameter from baseline to post shear stress for an individual measurement. Follow up measurements were obtained in intervention subjects 12 weeks later |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control Patients without intradialytic hypertension defined as average pre to post hemodialysis SBP falling \>10 mmhg for more than 4/6 of the last dialysis treatment sessions | 25 |
| Intervention Patients with intradialytic hypertension defined as average pre to post hemodialysis SBP elevation of \>10 mmhg for more than 4/6 of the last dialysis treatment sessions
Carvedilol: Carvedilol 6.25 mg BID titrated weekly to maximum of 50 mg bid | 25 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 5 |
Baseline characteristics
| Characteristic | Control | Total | Intervention |
|---|---|---|---|
| Age, Continuous | 55.1 years STANDARD_DEVIATION 7.9 | 54.5 years STANDARD_DEVIATION 9 | 53.9 years STANDARD_DEVIATION 11.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 31 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 19 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 19 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 31 Participants | 16 Participants |
| Region of Enrollment United States | 25 Participants | 50 Participants | 25 Participants |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 20 Participants | 40 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 0 / 25 | 22 / 25 |
| serious Total, serious adverse events | 0 / 25 | 5 / 25 |
Outcome results
Primary
Endothelial Progenitor Cells
1. ALDH bright cells reported as percentage of mononuclear cells. These were assayed using flow cytometry 2. CD34/CD133 endothelial progenitor cells reported as percentage of mononuclear cells. These were assayed using flow cytometry
Time frame: 12 weeks
Population: Follow up measurements were only obtained in the intervention subjects receiving carvedilol
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control | Endothelial Progenitor Cells | Baseline ALDH bright | 0.052 % of mononuclear cells |
| Control | Endothelial Progenitor Cells | Baseline CD34/CD133 endothelial progenitor cells | 0.059 % of mononuclear cells |
| Intervention | Endothelial Progenitor Cells | Baseline ALDH bright | 0.034 % of mononuclear cells |
| Intervention | Endothelial Progenitor Cells | Follow up ALDH bright | 0.027 % of mononuclear cells |
| Intervention | Endothelial Progenitor Cells | Baseline CD34/CD133 endothelial progenitor cells | 0.033 % of mononuclear cells |
| Intervention | Endothelial Progenitor Cells | Follow up CD34/CD133 | 0.029 % of mononuclear cells |
Secondary
Flow Mediated Vasodilation
Measured as percent change in brachial artery diameter from baseline to post shear stress for an individual measurement. Follow up measurements were obtained in intervention subjects 12 weeks later
Time frame: 12 weeks
Population: Follow up measurements were only obtained in intervention subjects receiving carvedilol
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Flow Mediated Vasodilation | Baseline FMD | 1.67 % dilation from baseline | Standard Deviation 1.24 |
| Intervention | Flow Mediated Vasodilation | Baseline FMD | 1.03 % dilation from baseline | Standard Deviation 0.7 |
| Intervention | Flow Mediated Vasodilation | Follow Up FMD | 1.4 % dilation from baseline | Standard Deviation 0.84 |