RAS Blockade at Bedtime Versus on Awakening for Aldosterone Breakthrough

Not Applicable

Completed

• Conditions: Chronic Kidney Disease
• Interventions: Other: Randomization that determine the time of treatment

• Registration Number: NCT01805362
• Lead Sponsor: Centre Hospitalier Universitaire de Nice

Brief 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.

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 Timeline

• Study Start: 2013-02-27
• Study First Submitted: 2013-02-28
• Study First Submitted QC: 2013-03-05
• Study First Posted: 2013-03-06
• Primary Completion: 2014-04-24
• Study Completion: 2018-01-12
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-10
• Last Update Posted: 2024-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 104

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EVENING	Randomization that determine the time of treatment	Patients take their treatments(RAS blockers and diurectics)at bedtime
MORNING	Randomization that determine the time of treatment	patients continue to take their treatments (RAS blockers and diuretics) on awaking

Primary Outcome Measures

Name	Time	Method
Serum aldosterone levels at one year	Level change between baseline and one year

Secondary Outcome Measures

Name	Time	Method
Significant aldosterone breakthrough Significant aldosterone breakthrough	changes between baseline and one year	Significant aldosterone breakthrough defined by a \>10% increase of serum aldosterone levels over baseline values,
Serum aldosterone/renin ratio	level change between baseline and 12 months

Trial Locations

Locations (1)

Department of Nephrology, Nice University Hospital; 🇫🇷 Nice, France