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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02285920
Other study ID # 821193
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date November 2014
Est. completion date July 30, 2017

Study information

Verified date July 2019
Source University of Pennsylvania
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

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.


Recruitment information / eligibility

Status Completed
Enrollment 129
Est. completion date July 30, 2017
Est. primary completion date June 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years to 85 Years
Eligibility 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

Study Design


Intervention

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.

Locations

Country Name City State
United States Brigham and Women's Hospital Boston Massachusetts
United States Vanderbilt University Medical Center Nashville Tennessee
United States Kidney Research Institute, University of Washington Seattle Washington
United States The George Washington University Washington District of Columbia

Sponsors (5)

Lead Sponsor Collaborator
University of Pennsylvania Brigham and Women's Hospital, George Washington University, University of Washington, Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
Primary Study Drug Tolerability Tolerability is defined as number of participants who experienced permanent study drug discontinuation or dose reduction. 0 - 36 weeks
Primary 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
Primary 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 Safety - Number of Participants With Serious Hyperkalemia Number of patients with serious hyperkalemia requiring hospitalization, emergency/unscheduled dialysis or resin therapy 0 - 40 weeks
Secondary Safety - Hyperkalemia Requiring Adjustment in Treatment Hyperkalemia requiring adjustment in dialysate potassium concentration, or discontinuation of study medication 0 - 40 weeks
Secondary Safety - Inter- or Intra-dialytic Hypotension Inter- or intra-dialytic hypotension defined as:
Inter-dialytic: systolic blood pressure <90 mm Hg or inter-dialytic hypotension requiring adjustment in anti-hypertensive medications or treatment in a hospital or emergency room.
Intra-dialytic: systolic blood pressure <80 mm Hg during =3 dialysis sessions per 30-day period or treatment for either hypotension or symptoms of hypotension during =3 dialysis sessions per 30-day period
0 - 40 weeks
Secondary Safety - Cardiovascular Death Number of Cardiovascular deaths defined as death due to myocardial infarction, congestive heart failure, cardiac valvular disease, arrhythmia, sudden death, stroke, or peripheral arterial disease 0 - 40 weeks
Secondary Efficacy - Secondary Cardiac Outcome Measure - Left Ventricular Ejection Fraction (LVEF) Secondary outcome measures include other echocardiographic markers of systolic and diastolic function
• Change in left ventricular ejection fraction between Baseline and 36 weeks
Baseline - 36 weeks
Secondary Efficacy - Secondary Cardiac Outcome Measures Left Ventricular Mass Index (LVMI) Secondary outcome measures include other echocardiographic markers of systolic and diastolic function,
• Change in left ventricular mass index (LVMI) between baseline and 36 weeks
Baseline - 36 weeks
Secondary Efficacy - Secondary Cardiac Outcome Measures - Ratio of Mitral Peak Velocity to Diastolic Mitral Annular Velocity (E/E') Secondary outcome measures include other echocardiographic markers of systolic and diastolic function,
• E/E' is the ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E')
Baseline - 36 weeks
Secondary Efficacy - Secondary Cardiac Outcome Measures - Left Ventricular Global Longitudinal Strain (LVGLS) Secondary outcome measures include other echocardiographic markers of systolic and diastolic function,
• Change in myocardial strain and strain rate between baseline and 36 weeks
Baseline - 36 weeks
Secondary Safety - Combined Incidence of Potassium >6.5 mEq/L or Serious Hyperkalemia The number of participants who had serum potassium >6.5 mEq/L or serious hyperkalemia was assessed by treatment arm. 0 - 40 Weeks
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