Clinical trial NCT01100203: Aldosterone Blockade in Chronic Kidney Disease: Influence on Arterial Stiffness and Kidney Function
Official title: Aldosterone Blockade in Chronic Kidney Disease. Influence on Arterial Stiffness and Kidney Function
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Chronic Kidney Disease
Keywords: aldosterone receptor inhibition
arterial stiffness
ambulatory arterial stiffness index
Lead sponsor: Herlev Hospital
Sponsor class: OTHER
Collaborators: name: Rigshospitalet, Denmark
First posted: 2010-04-08
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients with Chronic Kidney Disease (CKD) have a poor prognosis primarily due to cardiovascular disease. The cardiovascular risk can be assessed by measurements of arterial stiffness. A decrease in stiffness has been shown to decrease the risk of cardiovascular disease as well as death. Most of the CKD population also have hypertension and the control of blood pressure is one of the corner stones in inhibition of disease progression. Using drugs that specifically block the renin-angiotensin-system for blood pressure control has been shown to have a beneficial impact on inhibition of progression beyond that of the achieved blood pressure control. It has been reported that inhibition of the hormone aldosterone has a positive effect on survival in patients with heart failure, hypertension and diabetic as well as on-diabetic nephropathy.

This study undertakes the investigation of the influence on arterial stiffness of adding an aldosterone receptor inhibitor to the medication CKD patients are already taking. Besides the primary end point which is Pulse wave velocity (PWV), arterial stiffness is also quantified thorough ambulatory blood pressure measurements.


Eligibility criteria: Inclusion Criteria:

* ≥ 18 years age ≤ 80 years age
* voluntarily signed informed consent
* 15 ml/min/1,73 m2 ≤ estimated Glomerular Filtration Rate \< 60 ml/min/1,73 m2
* BP ≥ 130/80 mmHg or undergoing anti-hypertensive treatment

Exclusion Criteria:

* p-potassium is \> 5.0 mM
* allergy to contents
* treated with spironolactone
* treated with potent inhibitors of CYP3A4 (see SPC for details)
* treated with lithium, ciclosporin, tacrolimus, prednisolone, or other immunosuppressing drug
* inborn errors of metabolism (see SPC for details)
* pregnancy or lactation
* fertile woman, not using safe contraception devices
* dementia or other psychiatric disorder, making understanding of the study conditions impossible
* other severe, chronic illness besides CKD, including liver insufficiency, according to investigators' judgement
* vascular surgery including stenting or graft implantation on a. brachialis, aorta or the carotid arteries
* systolic BP \> 200 mmHg
* immeasurable pulse amplitude

Primary outcomes:
measure: Pulse wave velocity
timeFrame: 24 weeks
measure: Pulse Wave velocity
timeFrame: 12 weeks
measure: Pulse wave velocity
timeFrame: baseline
Secondary outcomes:
measure: Ambulatory arterial stiffness index
timeFrame: 24 weeks
measure: Pulse wave analysis
timeFrame: 24 weeks
measure: Albuminuria
timeFrame: baseline
measure: Pulse wave analysis
timeFrame: baseline
measure: Ambulatory arterial stiffness index
timeFrame: baseline
measure: Ambulatory arterial stiffness index
timeFrame: 12 weeks
measure: Pulse wave analysis
timeFrame: 12 weeks
measure: Albuminuria
timeFrame: 12 weeks
measure: Albuminuria
timeFrame: 24 weeks
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: baseline
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: 12 weeks
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: 24 weeks
measure: Plasma potassium
timeFrame: baseline
measure: Plasma potassium
timeFrame: week 1
measure: Plasma potassium
timeFrame: week 2
measure: Plasma potassium
timeFrame: week 4
measure: Plasma potassium
timeFrame: week 8
measure: Plasma potassium
timeFrame: week 12
measure: Plasma potassium
timeFrame: week 16
measure: plasma potassium
timeFrame: week 20
measure: plasma potassium
timeFrame: week 24
measure: Blood pressure
timeFrame: baseline
measure: Blood pressure
timeFrame: 12 weeks
measure: Blood pressure
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Herlev
country: Denmark
facility: Dept. Nephrology, Herlev Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
Study officials:
affiliation: Herlev Hospital
name: Lene Boesby, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC, Strippoli GF. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020 Oct 27;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4.
citation: Boesby L, Elung-Jensen T, Strandgaard S, Kamper AL. Eplerenone attenuates pulse wave reflection in chronic kidney disease stage 3-4--a randomized controlled study. PLoS One. 2013 May 21;8(5):e64549. doi: 10.1371/journal.pone.0064549. Print 2013.