Clinical trial NCT01805362: RAS Blockade at Bedtime Versus on Awakening for Aldosterone Breakthrough
Official title: RAS Blockade at Bedtime Versus on Awakening for the Prevention of Aldosterone Breakthrough
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2013-03-06
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility 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 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.

Primary outcomes:
measure: Serum aldosterone levels at one year
timeFrame: Level change between baseline and one year
Secondary outcomes:
measure: Serum aldosterone/renin ratio
timeFrame: level change between baseline and 12 months
measure: Significant aldosterone breakthrough Significant aldosterone breakthrough
timeFrame: changes between baseline and one year
Other outcomes:
Locations:
city: Nice
country: France
facility: Department of Nephrology, Nice University Hospital
Study officials:
affiliation: Nice University Hospital
name: Vincent ESNAULT, MD
role: PRINCIPAL_INVESTIGATOR
References: