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

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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Chronic Kidney Disease, Proteinuria

Intervention / Treatment
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* Drug: aliskiren, eplerenon, telmisartan


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: C - A - B<br>(A) telmisartan 80 mg + aliskiren 300 mg - (B) telmisartan 80 mg + eplerenon 50 mg - (C) telmisartan 160 mg | Drug: aliskiren, eplerenon, telmisartan<br>* aliskiren (Rasilez 300 mg, Novartis Europharm eplerenon (Inspra 50 mg, Pfizer Europe) telmisartan (Micardis 80 mg, Boehringer Ingelheim)<br>|
| Active Comparator: B - A - C<br>(A) telmisartan 80 mg + aliskiren 300 mg - (B) telmisartan 80 mg + eplerenon 50 mg - (C) telmisartan 160 mg | Drug: aliskiren, eplerenon, telmisartan<br>* aliskiren (Rasilez 300 mg, Novartis Europharm eplerenon (Inspra 50 mg, Pfizer Europe) telmisartan (Micardis 80 mg, Boehringer Ingelheim)<br>|
| Active Comparator: A - B - C<br>(A) telmisartan 80 mg + aliskiren 300 mg - (B) telmisartan 80 mg + eplerenon 50 mg - (C) telmisartan 160 mg | Drug: aliskiren, eplerenon, telmisartan<br>* aliskiren (Rasilez 300 mg, Novartis Europharm eplerenon (Inspra 50 mg, Pfizer Europe) telmisartan (Micardis 80 mg, Boehringer Ingelheim)<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aliskiren, eplerenon, telmisartan, direct renin inhibitor, ACE inhibitor, mineralocorticoid inhibitor, proteinuria, chronic kidney diseases, renin-angiotensin-aldosterone system