RAS Blockade at Bedtime Versus on Awakening for Aldosterone Breakthrough

Chronic Kidney Disease Clinical Trial

— IRAB2  

Official title:

RAS Blockade at Bedtime Versus on Awakening for the Prevention of Aldosterone Breakthrough

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01805362
• Other study ID #: 08-API-03
• Status: Completed
• Phase: N/A
• Start date: February 27, 2013
• Est. completion date: January 12, 2018

Study information

• Verified date: April 2024
• Source: Centre Hospitalier Universitaire de Nice
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Objective:

To show that the frequency of aldosterone breakthrough is lower when RAS blockers are given at bedtime compared to on awaking, and to analyze the determinants and consequences of aldosterone breakthrough.

Duration of the study: Inclusion 2 years, follow-up one year, total 3 years Design:

prospective, multicenter, randomized, controlled, open label, two parallel groups.

Main selection criteria:

Inclusion criteria

• Chronic kidney disease stage 3 to 4,

• ACEI (captopril, enalapril, or ramipril), and/or ARB (losartan, valsartan, or irbesartan) on awaking for at least three months,

• History of hypertension or proteinuria > 0,5 g/24h or g/g créatininurie.

Exclusion criteria

• Office blood pressure ≥ 160/100 mmHg,

• Anti-aldosterone (spironolactone, eplerenone) or potassium sparing diuretics (modamide, amiloride), or direct renin inhibitor.

Evaluation criteria:

Primary: Serum aldosterone levels at one year.

Secondary:

• Serum aldosterone/renin ratio,

• 24h urine aldosterone,

• Significant aldosterone breakthrough defined by a >10% increase of serum aldosterone levels over baseline values,

• Aldosterone breakthrough defined by an increase of serum aldosterone levels over baseline values,

• HbA1c,

• Urinary albumin/creatinine ratio (UACR) on spot morning urine samples,

• Systolic home blood pressure (SBP),

• Estimated glomerular filtration rate (eGFR) using the MDRD equation.

Description:

Rational:

Serum aldosterone levels may increase despite blockade of the renin angiotensin system (RAS) with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB). This aldosterone breakthrough might be associated with bad outcomes: left ventricular hypertrophy, proteinuria and progression of renal failure. Antihypertensive drugs are given either on awaking or at bedtime. RAS is stimulated during nighttime. RAS blockers and diuretics given on awaking may stimulate aldosterone synthesis, and favor aldosterone breakthrough.

Objective:

To show that the frequency of aldosterone breakthrough is lower when RAS blockers are given at bedtime compared to on awaking, and to analyze the determinants and consequences of aldosterone breakthrough.

Duration of the study: Inclusion 2 years, follow-up one year, total 3 years

Design: prospective, multicenter, randomized, controlled, open label, two parallel groups.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 104
• Est. completion date: January 12, 2018
• Est. primary completion date: April 24, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Chronic kidney disease stage 3 to 4,

• ACEI (captopril, enalapril, or ramipril), and/or ARB (losartan, valsartan, or irbesartan) on awaking for at least three months,

• History of hypertension or proteinuria > 0,5 g/24h or g/g creatininuria,

• Adult with social security insurance,

• Informed consent signed.

Exclusion Criteria:

• Office blood pressure = 160/100 mmHg,

• Pathology with life expectancy < 1 year,

• Anti-aldosterone (spironolactone, eplerenone) or potassium sparing diuretics (modamide, amiloride), or direct renin inhibitor.

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Other:
• Randomization that determine the time of treatment

Locations

Country	Name	City	State
France	Department of Nephrology, Nice University Hospital	Nice

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nice

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum aldosterone levels at one year		Level change between baseline and one year
Secondary	Serum aldosterone/renin ratio		level change between baseline and 12 months
Secondary	Significant aldosterone breakthrough Significant aldosterone breakthrough	Significant aldosterone breakthrough defined by a >10% increase of serum aldosterone levels over baseline values,	changes between baseline and one year