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Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent ESRD Trial (SPin-D)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02285920
Recruitment Status : Active, not recruiting
First Posted : November 7, 2014
Last Update Posted : July 7, 2017
Sponsor:
Collaborators:
Information provided by (Responsible Party):

October 13, 2014
November 7, 2014
July 7, 2017
November 2014
June 2017   (Final data collection date for primary outcome measure)
  • Safety [ Time Frame: 0 - 40 weeks ]
    a) The incidence of serum potassium >6.5 mEq/L
  • Safety [ Time Frame: 0 - 40 weeks ]
    b) The incidence of serious hypotension not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection)
  • Tolerability [ Time Frame: 0 - 36 weeks ]
    Tolerability will be assessed on the basis of whether participants can continue the assigned dose throughout the entire treatment period. Any reduction in dose of study medication will be considered a failure of primary tolerability.
  • Efficacy [ Time Frame: 0 - 36 weeks ]
    Change in mitral annular E' velocity will be measured using Tissue Doppler Index (TDI) echocardiography of the left ventricle as a measure of diastolic function and as surrogate measure of left ventricular fibrosis.
  • Feasibility [ Time Frame: 0 - 40 weeks ]
    An objective of this study is to assess the feasibility of conducting a full-scale mortality-powered trial. Feasibility will be assessed based on recruitment, dropout and loss to follow-up rates.
Same as current
Complete list of historical versions of study NCT02285920 on ClinicalTrials.gov Archive Site
  • Safety [ Time Frame: 0 - 40 weeks ]
    1. Potassium level >6.5 mEq/L
    2. Serious hypotension requiring hospitalization or emergency dept. treatment
    3. Serious hyperkalemia requiring hospitalization, emergency/unscheduled dialysis or resin therapy
    4. Combined incidence of potassium >6.5 mEq/L or serious hyperkalemia requiring hospitalization, emergency/unscheduled dialysis or resin therapy
    5. Treatment-emergent events - combined incidence of death, myocardial infarction, stroke, hospitalizations, potassium greater than 6.5 mEq/L, serious hyperkalemia, serious hypotension
    6. Individual components of the treatment-emergent endpoint
    7. Cardiovascular death
    8. Hyperkalemia requiring adjustment in dialysate potassium concentration, or discontinuation of study medication
    9. Proportion of dialysis sessions using 1 mEq/L potassium dialysis solution bath
    10. Within-patient variability in serum potassium concentration
    11. Symptomatic inter- or intra-dialytic hypotension
  • Efficacy [ Time Frame: 0 - 36 weeks ]

    Secondary outcome measures include other echocardiographic markers of systolic and diastolic function, circulating markers of fibrosis and, in a sub-study, heart rate variability as assessed by Holter monitoring and coronary flow reserve (CFR) as assessed by myocardial positron emission tomography (PET).

    • Change in left ventricular mass index (LVMI) between 0 and 36 weeks
    • Change in ejection fraction between 0 and 36 weeks
    • Change in myocardial strain and strain rate between 0 and 36 weeks
    • Change in cardiac fibrosis markers between baseline and 36 weeks
    • Change in inflammatory markers between baseline and 36 weeks
    • Change in oxidative stress markers between baseline and 36 weeks
    • Change in CFR between baseline and 36 weeks
    • Association between change in CFR and change in E'
    • Heart rate variability
    • Serious arrhythmia
Same as current
Not Provided
Not Provided
 
Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent ESRD Trial
Safety and Cardiovascular Efficacy of Spironolactone in Dialysis-Dependent End-Stage Renal Disease (ESRD) (SPin-D) 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.
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
End-Stage Renal Disease
Drug: Spironolactone
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.
  • Active Comparator: Spironolactone 12.5 mg
    Participants will initiate treatment at 12.5 mg daily and continue at this dose for 36 weeks.
    Intervention: Drug: Spironolactone
  • Active Comparator: Spironolactone 25 mg
    Participants will initiate treatment at 12.5 mg daily for 2 weeks at which time the dose will be increased to 25 mg daily for a total treatment time of 36 weeks.
    Intervention: Drug: Spironolactone
  • Active Comparator: Spironolactone 50 mg
    Participants will initiate treatment at 12.5 mg daily for 2 weeks at which time the dose will be increased to 25 mg daily for 2 weeks, and increased to 50 mg daily for a total treatment time of 36 weeks.
    Intervention: Drug: Spironolactone
  • Placebo Comparator: Placebo
    Participants will be treated with placebo for 36 weeks.
    Intervention: Drug: Spironolactone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
129
September 2018
June 2017   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 85 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT02285920
821193
Yes
Not Provided
Not Provided
University of Pennsylvania
University of Pennsylvania
  • Brigham and Women's Hospital
  • George Washington University
  • Vanderbilt University
  • University of Washington
Principal Investigator: Laura M Dember, MD University of Pennsylvania
University of Pennsylvania
July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP