Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent ESRD Trial
Condition: End-Stage Renal Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic
Intervention: Spironolactone
Intervention description: The trial will be conducted in 2 phases - a dose escalation phase (6 weeks) and a treatment phase (30 weeks). At the end of the dose escalation phase, participants will continue treatment based on the randomized dose assignment for an additional 30 weeks (treatment phase) such that the total duration of study medication is 36 weeks.
Intervention MeSH terms: Spironolactone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 129.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: hemodialysis; spironolactone; cardiac fibrosis; diastolic function

Summary:

      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.
    

Eligibility criteria:

        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