Aldosterone Blockade in Chronic Kidney Disease: Influence on Arterial Stiffness and Kidney Function (ALBLOCK-2)

Aldosterone Blockade in Chronic Kidney Disease. Influence on Arterial Stiffness and Kidney Function

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Eplerenone

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Herlev, Denmark, DK-2730
    • Herlev Hospital
  • Herlev, Denmark, DK-2730
    • Dept. Nephrology, Herlev Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
NO_INTERVENTION: Control
ACTIVE_COMPARATOR: Treatment	Drug: Eplerenone; 25 mg once daily 1 week, then 50 mg once daily for another 23 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulse wave velocity	Pulse wave velocity measured using the SphygmoCor device.	24 weeks
Pulse Wave velocity		12 weeks
Pulse wave velocity		baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood pressure		12 weeks
Ambulatory arterial stiffness index	24 hour ambulatory blood pressure measurements, give rise to the index, which is a secondary measure of arterial compliance.	24 weeks
Pulse wave analysis	Parameters are Augmentation Index, subendocardial viability ratio, pulse, time to reflection, ejection duration.	24 weeks
Albuminuria	Will be calculated from 24 hour urine collections.	baseline
Pulse wave analysis		baseline
Ambulatory arterial stiffness index		baseline
Ambulatory arterial stiffness index		12 weeks
Pulse wave analysis		12 weeks
Albuminuria		12 weeks
Albuminuria		24 weeks
Estimated glomerular filtration rate (eGFR)	Estimated glomerular filtration rate (eGFR) will be calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.	baseline
Estimated glomerular filtration rate (eGFR)		12 weeks
Estimated glomerular filtration rate (eGFR)		24 weeks
Plasma potassium		baseline
Plasma potassium		week 1
Plasma potassium		week 2
Plasma potassium		week 4
Plasma potassium		week 8
Plasma potassium		week 12
Plasma potassium		week 16
plasma potassium		week 20
plasma potassium		week 24
Blood pressure	BP will be measured at all visits	baseline
Blood pressure		24 weeks

Collaborators and Investigators

• Sponsor: Lene Boesby
• Collaborators: Rigshospitalet, Denmark
• Investigators: Principal Investigator: Lene Boesby, MD, Herlev Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): January 1, 2012
• Study Completion (ACTUAL): February 1, 2012

Study Registration Dates

• First Submitted: April 6, 2010
• First Submitted That Met QC Criteria: April 7, 2010
• First Posted (ESTIMATE): April 8, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): February 8, 2012
• Last Update Submitted That Met QC Criteria: February 7, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: arterial stiffness; aldosterone receptor inhibition; ambulatory arterial stiffness index
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Antihypertensive Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Eplerenone
• Other Study ID Numbers: ALBLOCK-2