Chronic Kidney Disease, Poorly-Controlled Hypertension
Conditions
Keywords
hypertension, kidney disease
Brief summary
It is estimated that in the United States there are approximately 8 million individuals with moderate to severe chronic kidney disease (CKD), not on dialysis. Volume expansion plays an important role in the pathogenesis of hypertension in patients with CKD. For this pilot study, the investigators hypothesize that administration of chlorthalidone among patients with moderate to severe CKD will improve blood pressure (BP).
Interventions
DRUGChlorthalidone
Sponsors
Indiana University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than 18 years. * Estimated glomerular filtration rate (eGFR) ≤ 45 ml/min/1.73m2 but ≥20 mL/min/1.73m2. * Poorly controlled blood pressure by 24-hour ambulatory blood pressure (BP) monitoring. * Treated hypertension: use of at least one antihypertensive drug. One of the drugs should be either an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB). If these are contraindicated then use of a beta-blocker is required.
Exclusion criteria
* Use of thiazide or thiazide-like drugs in the previous 3 months. * Use of furosemide in a dose \>200 mg/d. * Ambulatory BP of either ≥160 systolic or ≥100 mmHg by 24-hour ambulatory BP monitoring. * Expected to receive renal replacement therapy within the next 3 months. * Vascular event such as myocardial infarction, heart failure hospitalization, or stroke within 3 months prior to randomization. * Pregnant or breastfeeding women or women who are planning to become pregnant or those not using a reliable form of contraception (oral contraceptives. condoms and diaphragms will be considered reliable). * Known hypersensitivity to thiazide or sulfa drugs. * Organ transplant recipient or therapy with immunosuppressive agents. Nasal or inhaled corticosteroids will be permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change of Systolic Ambulatory Blood Pressure From Baseline to 12 Weeks | Baseline and 12 weeks after intervention |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from the VA Medical Center from Sept. 18, 2012 - May 15, 2013. Eligible subjects were ≥ 18 years of age with estimated glomerular filtration rate ≤ 45 but \> 20 mL/min/1.73m2. The study initially recruited subjects with resistant hypertension but was amended to include those with poorly controlled but treated hypertension.
Pre-assignment details
Prior to assignment, participants completed home blood pressure monitoring, ambulatory blood pressure monitoring, and a two-week run-in period, during which all subjects received a standard anti-hypertensive regimen based on the existing regimen of the subject.
Participants by arm
| Arm | Count |
|---|---|
| Chlorthalidone Open-label, forced-titration of Chlorthalidone (25mg/day at baseline) | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Safety Endpoint | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Chlorthalidone |
|---|---|
| Age, Continuous | 67.5 years STANDARD_DEVIATION 10.2 |
| Chronic Kidney Disease (CKD) Stage Stage 3B | 4 participants |
| Chronic Kidney Disease (CKD) Stage Stage 4 | 8 participants |
| Chronic Kidney Disease (CKD) Stage Stage 5 | 2 participants |
| Estimated GFR | 26.8 mL/min/1.73m2 STANDARD_DEVIATION 8.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 14 |
| serious Total, serious adverse events | 2 / 14 |
Outcome results
Primary
Change of Systolic Ambulatory Blood Pressure From Baseline to 12 Weeks
Time frame: Baseline and 12 weeks after intervention
Population: Intention to treat analysis (includes completers and non-completers)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Chlorthalidone | Change of Systolic Ambulatory Blood Pressure From Baseline to 12 Weeks | -10.5 mmHg | Standard Deviation 4.2 |
p-value: 0.01Mixed Models Analysis