Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent ESRD Trial
Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent ESRD Trial
The SPin-D Trial is a phase II randomized, double-blind, placebo-controlled, multi-center
 study of spironolactone (SPL) for patients with hemodialysis-dependent end-stage renal
 disease.
The primary objective of this study is to characterize the safety and tolerability of
 multiple doses of chronic SPL therapy compared with placebo in maintenance hemodialysis
 patients and to assess the feasibility of conducting a full-scale, mortality-powered trial of
 SPL. The effects of SPL compared with placebo on multiple cardiovascular efficacy parameters
 will also be analyzed. The primary efficacy parameter will be the change in the E'
 measurement on tissue Doppler echocardiography (TDI) as an index of diastolic function and a
 surrogate for myocardial fibrosis. Secondary cardiac parameters of interest that will be
 studied in the overall population or in sub-studies include heart rate variability,
 circulating markers of fibrosis, and coronary flow reserve (CFR) as an index of microvascular
 function. These parameters are designed to broaden insight into the potential effects of SPL
 on cardiac structure and function in individuals with dialysis-dependent ESRD and to assess
 the feasibility of conducting a full-scale, mortality-powered trial.
Inclusion Criteria:

 1. Maintenance hemodialysis therapy for end-stage renal disease

 2. Age 18-85 years

 3. ≥3 calendar months since dialysis initiation. Note if a patient has been on dialysis
 for ≥3 but less than 6 calendar months, there must be no hospitalizations during the 6
 weeks prior to screening, and no change in estimated dry weight (EDW) within 2 weeks
 of the screening date.

 4. For women of childbearing potential, willingness to use a highly effective method of
 birth control for up to 4 weeks after the last dose to study drug.

 5. Ability to provide informed consent

 Exclusion Criteria:

 1. Serum potassium ≥6.5 mEq/L within the 3 months prior to screening

 2. Serum potassium level ≥6.0 mEq/L within 2 weeks prior to the baseline visit. If a
 potassium value is not available through routine clinical care during this 2-week
 period a potassium measurement will be performed as a research test.

 3. Unscheduled dialysis for hyperkalemia within the 3 months prior to screening

 4. Pre-dialysis systolic blood pressure <100 mm Hg within 2 weeks prior to screening or
 at the baseline visit

 5. 2 or more dialysis sessions within the month prior to screening with either 2
 intra-dialytic measurements of systolic blood pressure <80 mm Hg or muscle cramping,
 light-headedness, nausea or hypotension requiring infusion of saline or other
 intervention directed at hypotension

 6. Current dual use of angiotensin converting enzyme inhibitor (ACEI) and angiotensin
 receptor blocker (ARB)

 7. Current use of digoxin

 8. Current use of spironolactone or eplerenone

 9. Allergy to spironolactone

 10. Inability to maintain dialysis machine blood flow ≥300 mL/min during any of the most
 recent 3 dialysis sessions prior to the screening visit as an indicator of vascular
 access dysfunction

 11. Mitral valve repair or replacement

 12. Severe mitral valve disease by echocardiography, coronary angiography or cardiac
 magnetic resonance imaging

 13. Anticipated kidney transplant, change to peritoneal dialysis, or transfer to another
 dialysis unit within 9 months

 14. Expected survival <9 months

 15. Pregnancy, anticipated pregnancy, or breastfeeding

 16. Incarceration

 17. Participation in another intervention study