Clinical trial NCT01691053: Mineralocorticoid Receptor Antagonists in End Stage Renal Disease
Official title: Phase II Trial to Evaluate the Efficacy and Safety of Spironolactone in Hemodialysis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: End Stage Renal Disease / Hemodialysis
Keywords: End stage renal disease
Hemodialysis
Spironolactone
Left ventricular hypertrophy
Lead sponsor: Wuerzburg University Hospital
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
name: Clinical Trial Center Wuerzburg (CTCW)
First posted: 2012-09-24
Enrollment: 118
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Left Ventricular Mass Index
timeFrame: 9 months
Secondary outcomes:
measure: Cardiac function parameters
timeFrame: 9 months
measure: Office and 24h blood pressure
timeFrame: 9 months
measure: Clinical measures of heart failure severity
timeFrame: 9 months
measure: Vascular function
timeFrame: 9 months
measure: Biomarkers of heart failure, inflammation and fibrosis
timeFrame: 9 months
measure: Quality of Life - Hospital Anxiety and Depression Scale (HADS)
timeFrame: 9 months
measure: Cardiac death and/or hospitalization for heart failure
timeFrame: 9 months
measure: Safety measures
timeFrame: 9 months
measure: Quality of Life - Kidney Disease Quality of Life Instrument (KDQOL-SF36)
timeFrame: 9 months
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: University Hospital Erlangen-Nürnberg
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
city: Wuerzburg
country: Germany
facility: University Hospital Wuerzburg
Study officials:
affiliation: University Hospital Wuerzburg
name: Christoph Wanner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Wuerzburg
name: Fabian Hammer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Wuerzburg
name: Vera Krane, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Hauser T, Dornberger V, Malzahn U, Grebe SJ, Liu D, Stork S, Nauck M, Friedrich N, Dorr M, Wanner C, Krane V, Hammer F; MiREnDa Study Group; Collaborating investigators (sites). The effect of spironolactone on diastolic function in haemodialysis patients. Int J Cardiovasc Imaging. 2021 Jun;37(6):1927-1936. doi: 10.1007/s10554-021-02176-5. Epub 2021 Feb 5.
citation: Grebe SJ, Malzahn U, Donhauser J, Liu D, Wanner C, Krane V, Hammer F. Quantification of left ventricular mass by echocardiography compared to cardiac magnet resonance imaging in hemodialysis patients. Cardiovasc Ultrasound. 2020 Sep 16;18(1):39. doi: 10.1186/s12947-020-00217-y.
citation: Hammer F, Krane V, Stork S, Roser C, Hofmann K, Pollak N, Allolio B, Wanner C. Rationale and design of the Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease Study (MiREnDa). Nephrol Dial Transplant. 2014 Feb;29(2):400-5. doi: 10.1093/ndt/gft409. Epub 2013 Oct 28.