The Effect of Various Types of the Renin-angiotensin-aldosterone System Blockade on Proteinuria

The Effect of Various Types of the Renin-angiotensin-aldosterone System Blockade on Proteinuria in Chronic Non-diabetic Kidney Disease: a Double-blind Cross-over Randomised Controlled Study

The main purpose of the study is to compare the effects of three different types of RAAS blockade on 24 hours proteinuria in patients with non-diabetic chronic kidney disease.

Study Overview

• Status: Completed
• Conditions: Proteinuria; Chronic Kidney Disease
• Intervention / Treatment: Drug: aliskiren, eplerenon, telmisartan

Detailed Description

Pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) is the main target of therapy to reduces both proteinuria and the rate of decline of the glomerular filtration rate in non-diabetic chronic renal diseases. Despite recent progress, however, there is still no optimal therapy that can stop the progression of these nephropathies. Therefore, it is necessary to optimize such treatment for further improving renal outcome.

The aim of the present study was to compare the effects of three different types of RAAS blockade: (1) mineralocorticoid receptor blocker (MRB) + angiotensin receptor antagonist (ARA); (2) direct renin inhibitor (DRI) + ARA and (3) double maximal dose of ARA on 24 hours proteinuria in patients with non-diabetic chronic kidney disease

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 18-65 years
• chronic non-diabetic proteinuric nephropathy
• chronic kidney disease stage 1-3
• stable proteinuria above 500 mg/24 hours
• blood pressure above 125/75 mmHg and below 150/95 mmHg
• no steroids or other immunosuppressive treatment for a minimum of six months before the study

Exclusion Criteria:

• unstable coronary heart disease
• decompensated congestive heart failure in the previous 6 months
• episode of malignant hypertension or stroke in the history
• diabetes
• creatinine clearance below 30 ml/min
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: C - A - B; (A) telmisartan 80 mg + aliskiren 300 mg - (B) telmisartan 80 mg + eplerenon 50 mg - (C) telmisartan 160 mg	Drug: aliskiren, eplerenon, telmisartan; aliskiren (Rasilez 300 mg, Novartis Europharm eplerenon (Inspra 50 mg, Pfizer Europe) telmisartan (Micardis 80 mg, Boehringer Ingelheim)
ACTIVE_COMPARATOR: B - A - C; (A) telmisartan 80 mg + aliskiren 300 mg - (B) telmisartan 80 mg + eplerenon 50 mg - (C) telmisartan 160 mg	Drug: aliskiren, eplerenon, telmisartan; aliskiren (Rasilez 300 mg, Novartis Europharm eplerenon (Inspra 50 mg, Pfizer Europe) telmisartan (Micardis 80 mg, Boehringer Ingelheim)
ACTIVE_COMPARATOR: A - B - C; (A) telmisartan 80 mg + aliskiren 300 mg - (B) telmisartan 80 mg + eplerenon 50 mg - (C) telmisartan 160 mg	Drug: aliskiren, eplerenon, telmisartan; aliskiren (Rasilez 300 mg, Novartis Europharm eplerenon (Inspra 50 mg, Pfizer Europe) telmisartan (Micardis 80 mg, Boehringer Ingelheim)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in urinary albumin-to-creatinine ratio (UACR) between treatment arms	changes of UACR	baseline and the end of 8 week treatments

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in transforming growth factor beta (TGF-beta) between treatment arms	Changes of urinary excretion of transforming growth factor beta (TGF-beta)	baseline and the end of 8 week treatments
Difference in serum potassium and creatinine between treatment arms		baseline and the end of 8 week treatments

Collaborators and Investigators

• Sponsor: Medical University of Gdansk
• Investigators: Principal Investigator: Bolesław Rutkowski, Professor, Departmen of Nephrology, Transplantation adn Internal Medicine, Medical University of Gdańsk, Poland

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (ACTUAL): May 1, 2011
• Study Completion (ACTUAL): November 1, 2011

Study Registration Dates

• First Submitted: February 11, 2012
• First Submitted That Met QC Criteria: February 28, 2012
• First Posted (ESTIMATE): February 29, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): February 29, 2012
• Last Update Submitted That Met QC Criteria: February 28, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: proteinuria; ACE inhibitor; aliskiren; renin-angiotensin-aldosterone system; telmisartan; chronic kidney diseases; direct renin inhibitor; eplerenon; mineralocorticoid inhibitor
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Renal Insufficiency; Urination Disorders; Kidney Diseases; Renal Insufficiency, Chronic; Proteinuria; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Telmisartan
• Other Study ID Numbers: ST-4/Aliskiren/2011