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Phase 2 Completed N=129 Randomized Quadruple-blind Treatment

Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent ESRD Trial

Source: ClinicalTrials.gov NCT02285920 ↗
Enrolled (actual)
129
Serious AEs
50.4%
Results posted
Jul 2019
Primary outcomePrimary: Safety - Number of Participants With Serum Potassium >6.5 mEq/L — 9; 4; 4; 8 Participants

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.

Outcome Measures

OutcomeResultp-value
PRIMARY
Safety - Number of Participants With Serum Potassium >6.5 mEq/L
9; 4; 4; 8
PRIMARY
Safety - Participants With Serious Hypotension
0; 2; 0; 3
PRIMARY
Study Drug Tolerability
16; 5; 6; 8
PRIMARY
Efficacy - Change in Mitral Annular E' Velocity
7.4; 7.6; 7.8; 7.0; 7.5; 7.4
PRIMARY
Feasibility of Conducting a Full-scale Mortality-powered Trial
2; 2; 2; 0; 0; 0
SECONDARY
Safety - Number of Participants With Serious Hyperkalemia
6; 2; 0; 7
SECONDARY
Safety - Hyperkalemia Requiring Adjustment in Treatment
13; 2; 5; 7
SECONDARY
Safety - Inter- or Intra-dialytic Hypotension
3; 1; 1; 0; 20; 9
SECONDARY
Safety - Cardiovascular Death
1; 0; 2; 1
SECONDARY
Efficacy - Secondary Cardiac Outcome Measure - Left Ventricular Ejection Fraction (LVEF)
68.9; 65.9; 66.0; 68.2; 70.7; 66.9
SECONDARY
Efficacy - Secondary Cardiac Outcome Measures Left Ventricular Mass Index (LVMI)
105.2; 115.5; 116.4; 106.3; 94.8; 104.6
SECONDARY
Efficacy - Secondary Cardiac Outcome Measures - Ratio of Mitral Peak Velocity to Diastolic Mitral Annular Velocity (E/E')
10.7; 11.8; 9.2; 12.5; 11.5; 12.2
SECONDARY
Efficacy - Secondary Cardiac Outcome Measures - Left Ventricular Global Longitudinal Strain (LVGLS)
-17.2; -16.7; -17.2; -17.4; -18.1; -17.0
SECONDARY
Safety - Combined Incidence of Potassium >6.5 mEq/L or Serious Hyperkalemia
13; 5; 5; 10

Eligibility Criteria

Inclusion Criteria

  • Maintenance hemodialysis therapy for end-stage renal disease
  • Age 18-85 years
  • ≥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.
  • 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.
  • Ability to provide informed consent

Exclusion Criteria

  • Serum potassium ≥6.5 mEq/L within the 3 months prior to screening
  • 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.
  • Unscheduled dialysis for hyperkalemia within the 3 months prior to screening
  • Pre-dialysis systolic blood pressure <100 mm Hg within 2 weeks prior to screening or at the baseline visit
  • 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
  • Current dual use of angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB)
  • Current use of digoxin
  • Current use of spironolactone or eplerenone
  • Allergy to spironolactone
  • 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
  • Mitral valve repair or replacement
  • Severe mitral valve disease by echocardiography, coronary angiography or cardiac magnetic resonance imaging
  • Anticipated kidney transplant, change to peritoneal dialysis, or transfer to another dialysis unit within 9 months
  • Expected survival <9 months
  • Pregnancy, anticipated pregnancy, or breastfeeding
  • Incarceration
  • Participation in another intervention study
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02285920). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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