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

NCT02285920 | Completed Phase 2 Results DMC

• 1 other identifier: 821193
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

End-Stage Renal Disease

Keywords

hemodialysis; spironolactone; cardiac fibrosis; diastolic function

Outcome Measures

Primary Outcomes (5)

• Safety - Number of Participants With Serum Potassium >6.5 mEq/L

  The number of participants who had serum potassium \>6.5 mEq/L was assessed by treatment arm.

  0 - 40 weeks

• Safety - Participants With Serious Hypotension

  The number of participants experiencing serious hypotension, defined as hypotension requiring hospitalization or ED visit and not attributable to overt sepsis, acute myocardial infarction, or other cardiovascular event (e.g. aortic dissection).

  0 - 40 weeks

• Study Drug Tolerability

  Tolerability is defined as number of participants who experienced permanent study drug discontinuation or dose reduction.

  0 - 36 weeks

• Efficacy - Change in Mitral Annular E' Velocity

  Change in mitral annular E' velocity measured using Tissue Doppler Index (TDI) echocardiography. Efficacy outcomes were considered exploratory with a goal of detecting signals rather than clearly demonstrating efficacy.

  Baseline to 36 weeks

• Feasibility of Conducting a Full-scale Mortality-powered Trial

  An objective of this study is to assess the feasibility of conducting a full-scale mortality-powered trial. Feasibility assessed based on recruitment, dropout and loss to follow-up rates.

  0 - 40 weeks

Secondary Outcomes (9)

• Safety - Number of Participants With Serious Hyperkalemia

  0 - 40 weeks

• Safety - Hyperkalemia Requiring Adjustment in Treatment

  0 - 40 weeks

• Safety - Inter- or Intra-dialytic Hypotension

  0 - 40 weeks

• Safety - Cardiovascular Death

  0 - 40 weeks

• Efficacy - Secondary Cardiac Outcome Measure - Left Ventricular Ejection Fraction (LVEF)

  Baseline - 36 weeks

Study Arms (4)

Spironolactone 12.5 mg

ACTIVE COMPARATOR

Participants will initiate treatment at 12.5 mg daily and continue at this dose for 36 weeks.

Drug: Spironolactone

Spironolactone 25 mg

ACTIVE COMPARATOR

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.

Drug: Spironolactone

Spironolactone 50 mg

ACTIVE COMPARATOR

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.

Drug: Spironolactone

Placebo

PLACEBO COMPARATOR

Participants will be treated with placebo for 36 weeks.

Drug: Spironolactone

Interventions

Spironolactone DRUG

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.

Placebo; Spironolactone 12.5 mg; Spironolactone 25 mg; Spironolactone 50 mg

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University of Pennsylvania: lead
• Brigham and Women's Hospital: collaborator
• George Washington University: collaborator
• Vanderbilt University: collaborator
• University of Washington: collaborator

Study Sites (4)

The George Washington University

Washington D.C., District of Columbia, 20037, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02120, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Kidney Research Institute, University of Washington

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• Hasegawa T, Nishiwaki H, Ota E, Levack WM, Noma H. Aldosterone antagonists for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2021 Feb 15;2(2):CD013109. doi: 10.1002/14651858.CD013109.pub2.

  PMID: 33586138 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Laura M. Dember, MD
• Organization: University of Pennsylvania

ldember@pennmedicine.upenn.edu

215-573-5264

Study Officials

• Laura M Dember, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2014
• First Posted: November 7, 2014
• Study Start: November 1, 2014
• Primary Completion: June 1, 2017
• Study Completion: July 30, 2017
• Last Updated: July 23, 2019
• Results First Posted: July 23, 2019

Record last verified: 2019-07

Locations

US (4)