End Stage Renal Disease / Hemodialysis
Conditions
Keywords
End stage renal disease, Hemodialysis, Spironolactone, Left ventricular hypertrophy
Brief summary
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.
Interventions
DRUGSpironolactone
50mg once daily
DRUGPlacebo
Placebo
Sponsors
German Federal Ministry of Education and Research
Clinical Trial Center Wuerzburg (CTCW)
Wuerzburg University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Mass Index | 9 months | as assessed by cardiac MRI |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Office and 24h blood pressure | 9 months | — |
| Clinical measures of heart failure severity | 9 months | New York Heart Association (NYHA) functional class, 6 minute walk test |
| Vascular function | 9 months | Carotid intima meda thickness, pulse wave analysis, carotid artery distensibility, flow mediated dilatation of the brachial artery |
| Biomarkers of heart failure, inflammation and fibrosis | 9 months | — |
| Cardiac function parameters | 9 months | cardiac volumes, systolic and diastolic function, cardiac output as measured by cardiac MRI and echocardiography |
| Cardiac death and/or hospitalization for heart failure | 9 months | — |
| Safety measures | 9 months | Pre-dialysis potassium levels, frequency of hyperkalemic episodes (K\>6.5mmol/l), measurement of residual kidney function (if applicable) |
| Quality of Life - Kidney Disease Quality of Life Instrument (KDQOL-SF36) | 9 months | Quality of life will be measured by analyzing KDQOL-SF36 |
| Quality of Life - Hospital Anxiety and Depression Scale (HADS) | 9 months | Quality of life will be measured by analyzing HADS |
Countries
Germany
Outcome results
None listed