RAS Blockade at Bedtime Versus on Awakening for Aldosterone Breakthrough (IRAB2)

RAS Blockade at Bedtime Versus on Awakening for the Prevention of 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.

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Other: Randomization that determine the time of treatment

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nice, France, 06000
    • Department of Nephrology, Nice University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MORNING; patients continue to take their treatments (RAS blockers and diuretics) on awaking	Other: Randomization that determine the time of treatment; Other Names: Randomization determine if the treatment will be taken in the morning or in the evening without changing the treatment
Experimental: EVENING; Patients take their treatments(RAS blockers and diurectics)at bedtime	Other: Randomization that determine the time of treatment; Other Names: Randomization determine if the treatment will be taken in the morning or in the evening without changing the treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum aldosterone levels at one year	Level change between baseline and one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum aldosterone/renin ratio		level change between baseline and 12 months
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

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Vincent ESNAULT, MD, Nice University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2013
• Primary Completion (Actual): April 24, 2014
• Study Completion (Actual): January 12, 2018

Study Registration Dates

• First Submitted: February 28, 2013
• First Submitted That Met QC Criteria: March 5, 2013
• First Posted (Estimated): March 6, 2013

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 08-API-03