Mineralocorticoid Receptor Antagonists in End Stage Renal Disease

Study Overview
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Brief Summary
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End stage renal disease (ESRD) patients exhibit an extraordinarily high annual mortality. Cardiovascular (CV) causes account for almost half of all-cause mortality. Increased left ventricular mass (LVM) is a common finding in ESRD patients on dialysis and is an independent predictor of survival. Yet, to date there is no established medical treatment to reduce CV morbidity and mortality in ESRD patients on hemodialysis. Blockade of aldosterone action by means of mineralocorticoid receptor antagonists (MRA) provides cardioprotection and improves outcome in heart failure patients. Furthermore, the MRA spironolactone has recently been shown to reduce LVM in patients with mild-to-moderate chronic kidney disease (CKD). The investigators here hypothesize that spironolactone treatment is cardioprotective by reducing LVM in ESRD patients on dialysis.

Official Title
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Phase II Trial to Evaluate the Efficacy and Safety of Spironolactone in Hemodialysis Patients

Conditions
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End Stage Renal Disease / Hemodialysis

Intervention / Treatment
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* Drug: Spironolactone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years Hemodialysis treatment for at least 3 months At least 3 dialysis sessions per week Written informed consent Exclusion Criteria: Contraindications for cardiac magnet resonance imaging (CMR) Mineralocorticoid receptor antagonist treatment within the last 6 months Estimated life expectancy < 12 months as judged by the nephrologist History of hyperkalemia, defined as pre-dialysis potassium > 6.5 mmol/l occurring ≥ 3 times within the last 3 months prior to enrolment. High risk to develop hyperkalemia defined as pre-dialysis potassium > 6.0 mmol/l Hypotension (systolic blood pressure < 100 mmHg) Planned kidney transplantation (living donor) within the prospected study duration Any acute illness within the last 4 weeks precluding a study participation as judged by the nephrologist Non-amenorrheic women with child bearing potential without reliable contraception, pregnancy/lactation Allergy/hypersensitivity to spironolactone Non-compliance suspected or demonstrated

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Spironolactone<br> | Drug: Spironolactone<br>* 50mg once daily<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular Mass Index | as assessed by cardiac MRI | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac function parameters | cardiac volumes, systolic and diastolic function, cardiac output as measured by cardiac MRI and echocardiography | 9 months | 
| Office and 24h blood pressure |  | 9 months | 
| Clinical measures of heart failure severity | New York Heart Association (NYHA) functional class, 6 minute walk test | 9 months | 
| Vascular function | Carotid intima meda thickness, pulse wave analysis, carotid artery distensibility, flow mediated dilatation of the brachial artery | 9 months | 
| Biomarkers of heart failure, inflammation and fibrosis |  | 9 months | 
| Quality of Life - Hospital Anxiety and Depression Scale (HADS) | Quality of life will be measured by analyzing HADS | 9 months | 
| Cardiac death and/or hospitalization for heart failure |  | 9 months | 
| Safety measures | Pre-dialysis potassium levels, frequency of hyperkalemic episodes (K>6.5mmol/l), measurement of residual kidney function (if applicable) | 9 months | 
| Quality of Life - Kidney Disease Quality of Life Instrument (KDQOL-SF36) | Quality of life will be measured by analyzing KDQOL-SF36 | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End stage renal disease, Hemodialysis, Spironolactone, Left ventricular hypertrophy