LOw DosE Spironolactone, chlorThAlidone oR Combination in CKD (LODESTAR) Trial
VA Office of Research and Development
Summary
The purpose of this research is to gather information on the safety and effectiveness of spironolactone and chlorthalidone for treatment of high blood pressure in patients with moderate to advanced CKD. Both drugs have been approved by the Food and Drug Administration (FDA) for the treatment of high blood pressure since 1960.
Description
Highly prevalent among patients with chronic kidney disease (CKD) , poor blood pressure (BP) control is a modifiable risk factor for both kidney failure progression and cardiovascular (CV) disease. Although the mineralocorticoid receptor antagonist (MRA) spironolactone (SPL) is recommended to treat resistant hypertension in patients with CKD, 34% discontinue SPL within 12 weeks, mostly due to hyperkalemia. The potassium (K) binding agent patiromer reduced the discontinuation rate to 14%, but the added expense and potential drug interactions are of concern. SPL, a steroidal MRA, reduces albumin…
Eligibility
- Age range
- 18–90 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Study is limited to US Veterans * GFR estimated by race-independent CKD-EPI formula \< 45 ml/min/1.73m2 but 15 mL/min/1.73m2 * Hypertension * The investigators will use clinic AOBP of at least 135/85 to define hypertension * 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 * Serum K 3.5 to 5.2 mEq/L at the time of randomization Exclusion Criteria: * Clinic AOBP of \>=160/100 mmHg * Use of: * SPL…
Interventions
- Drugphase 2A Chlorthalidone
very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks
- Drugphase 2A Spironolactone
very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks
- Drugphase 2A Chlorthalidone + Spironolactone
very low dose (VLD) x 6 weeks then low dose (LD) x 6 weeks
- Drugphase 2B Chlorthalidone LD + Spironolactone LD
compare combination LD with SPL LD at 12 weeks
Location
- Richard L. Roudebush VA Medical Center, Indianapolis, INIndianapolis, Indiana