Chronic Hypertension, Renal Insufficiency
Conditions
Keywords
Spironolactone, Chlorthalidone, Chronic Kidney Disease, Hypertension, Thiazide Diuretic, Potassium Sparring Diuretic
Brief summary
Highly prevalent among patients with chronic kidney disease (CKD) and poorly controlled blood pressure (BP), is a modifiable risk factor to abrogate both kidney failure progression and cardiovascular (CV) disease. Spironolactone (SPL), a mineralocorticoid receptor antagonist, is widely used to treat resistant hypertension, however one of the most common side effects is an increase of serum potassium (K). This side effect occurs frequently in those who suffer from CKD. Alternatively, chlorthalidone (CTD) is a thiazide-like diuretic used for treating hypertension and decreases serum K. In this pilot study, our goal is to assess whether the combination of SPL and CTD can improve BP control, while also reducing the risk of hyperkalemia over a period of 12 weeks. We hypothesize that among patients with CKD and poorly controlled hypertension, compared to SPL and placebo, treatment over 12 weeks with CTD will counter the hyperkalemia effect of SPL, and therefore the combination of SPL with CTD will result in a lower BP. This pilot study will be performed at Richard L. Roudebush VA in Indianapolis, Indiana.
Detailed description
This is a placebo-controlled, double-blind, randomized controlled trial of spironolactone (SPL) and chlorthalidone (CTD) in patients with CKD and poorly controlled hypertension
Interventions
DRUGSpironolactone
Study drugs will be increased if goal blood pressure is not achieved and/or serum potassium is not in safe clinical range (dosage of chlorthalidone/placebo not to exceed 25 mg daily; dosage of spironolactone not to exceed 50 mg daily).
DRUGChlorthalidone
Study drugs will be increased if goal blood pressure is not achieved and/or serum potassium is not in safe clinical range (dosage of chlorthalidone/placebo not to exceed 25 mg daily; dosage of spironolactone not to exceed 50 mg daily).
DRUGPlacebo
Study drugs will be increased if goal blood pressure is not achieved and/or serum potassium is not in safe clinical range (dosage of chlorthalidone/placebo not to exceed 25 mg daily; dosage of spironolactone not to exceed 50 mg daily).
Sponsors
Indiana Institute for Medical Research
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
19 Years to 110 Years
Healthy volunteers
No
Inclusion criteria
1. Age greater than 18 years. 2. GFR estimated by CKD-EPI formula \< 45 ml/min/1.73 m2 but ≥ 15 mL/min/1.73 m2 using IDMS-calibrated creatinine. 3. Hypertension. Using AOBP monitoring, BP of ≥ 130/80 mmHg. 4. Treatment with antihypertensive drugs: This would require the use of at least one antihypertensive drug. One of the drugs should be either an ACE inhibitor or ARB or a beta-blocker at the time of randomization. 5. Serum K 3.5 to 5.2 mEq/L at the time of randomization. In patients with eGFR \< 45 ml/min/1.73 m2 and serum K \> 5.2 mEq/L
Exclusion criteria
1. Use of spironolactone, eplerenone, amiloride, triamterene, thiazides, or thiazide-like drugs or the use of K supplements or K binders in the previous 12 weeks. 2. Expected to receive renal replacement therapy within the next 6 months. 3. Myocardial infarction, heart failure hospitalization, or stroke ≤ 12 weeks prior to randomization. 4. 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). 5. Known hypersensitivity to thiazide or spironolactone. 6. Clinic AOBP \<110 mmHg systolic at their first visit
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Systolic Automated Office Blood Pressure from baseline to 12 weeks between arms | Baseline to 12 Weeks |
Secondary
| Measure | Time frame |
|---|---|
| Change in logarithmically transformed albumin/creatinine ratio from baseline to 12 weeks between arms | Baseline to 12 Weeks |
Countries
United States
Contacts
Primary ContactRajiv Agarwal, MD
Backup ContactTimothy l Ramsey, MS/MBA
Outcome results
None listed