Ignite Creation Date:
2024-05-05 @ 11:58 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00199927
Status:
COMPLETED
Last Update Posted:
2010-04-28
First Post:
2005-09-12
Brief Title:
Statins in Proteinuric Nephropathies
Sponsor:
Mario Negri Institute for Pharmacological Research
Organization:
Mario Negri Institute for Pharmacological Research
Study Overview
Official Title:
A Prospective Randomized Multicenter Trial Testing the Antiproteinuric Effect of Statins Added to Combined ACE-inhibitor and Angiotensin Receptor Antagonist Therapy in Proteinuric Chronic Nephropathies
Status:
COMPLETED
Status Verified Date:
2010-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ESPLANADE
Brief Summary:
End stage renal disease ESRD is rapidly growing worldwide Patients with ESRD have increased morbidity and mortality mostly because of a dramatic excess of cardiovascular disease Thus preventing or limiting the progression of chronic nephropathies in addition to limit the incidence of ESRD may also postpone death Drugs that inhibit the renin angiotensin system such as Angiotensin-Converting-Enzyme inhibitors ACEi and Angiotensin II receptor antagonists ATA are reno- and cardio-protective in the long-term There are data that statinsin addition to limit cardiovascular events may have specific reno-protective properties
Thus we designed a study aimed to evaluate whether statins associated to ACEi and ATA may have an additional reno-protective effect
ESPLANADE is a multicenter prospective randomized parallel group study in which after 2 months treatment with ACEi and ATA two groups of 90 patients with or without type 2 diabetes are randomized to 6 months Fluvastatin 40 or 80 mgday treatment YES or NOTwenty Italian Nephrology Units are involved in the trial The study is fully coordinated by the Clinical Research Center for Rare Disease Aldo e Cele Daccò Villa Camozzi Ranica
Thus we designed a study aimed to evaluate whether statins associated to ACEi and ATA may have an additional reno-protective effect
ESPLANADE is a multicenter prospective randomized parallel group study in which after 2 months treatment with ACEi and ATA two groups of 90 patients with or without type 2 diabetes are randomized to 6 months Fluvastatin 40 or 80 mgday treatment YES or NOTwenty Italian Nephrology Units are involved in the trial The study is fully coordinated by the Clinical Research Center for Rare Disease Aldo e Cele Daccò Villa Camozzi Ranica
Detailed Description:
INTRODUCTION End stage renal disease ESRD is rapidly growing worldwide and costs of providing ESRD care will soon outstrip the available resources In addition to a poor quality of life patients with ESRD have 10 to 20 timer higher mortality than age- race- and gender-matched healthy controls with 50 of this excess burden being attributable to cardiovascular risk Thus preventing or limiting progression of chronic nephropathies may serve to limit the incidence not only of ESRD but also the excess of cardiovascular complications associated with chronic renal disease
Several data are available that proteinuria is an important determinant of progression to ESRD and a risk factor for increased cardiovascular morbidity and mortality Drugs such as Angiotensin-Converting-Enzyme inhibitors ACEi and Angiotensin II receptor antagonists ATA that decrease proteinuria are also reno- and cardio-protective in the long-termThe combination of these drugs may reduce proteinuria more effectively than the two drugs alone Preliminary data are also available that statins in addition to ameliorate the lipid profile may have specific renoprotective properties and combined to ACEi and ATA may synergize their antiproteinuric effects in experimental models of chronic renal diseaseMoreover the addition of statins to antihypertensive treatment with or without inhibitors of the renin-angiotensin system has an additive effect on reducing proteinuria also in humansWhether also in humans combining statins to ACEi and ATA may reduce proteinuria more effectively than ACEi and ATA alone is therefore worth investigating
AIMS Primary
- To assess whether statins combined to ACEi and ATA more effectively than ACEi and ATA alone reduce urinary protein excretion rate in chronic proteinuric nephropathies
Secondary
To assess the effect of statins combined to ACEi and ATA vs the combination of ACEi and ATA alone on other outcome variables including urinary proteincreatinine ratio glomerular filtration rate GFR lipid profile and in a subgroup endothelial function - To evaluate by correlation and multivariate analyses the relationship between baseline follow-up covariates and the above outcome variables in the study group as a whole and within each treatment group
To assess treatment tolerability DESIGN This is be a prospective randomized parallel group study in which following a 2 month Wash-out period from previous treatment if any with ACEi ATA potassium sparing diuretics or statins patients will enter a two-month Run-In phase on renin angiotensin system RAS inhibitor therapy ACE inhibition by benazepril for one month and ACE inhibition plus angiotensin II antagonism by combined treatment with benazepril and valsartan for one further month At completion of the Run-in period and after a baseline evaluation patients will be randomized to a six-month Treatment period with or without fluvastatin Regardless of the randomization group all patients will be offered optimal conservative treatment including optimal blood pressure controlsystolicdiastolic blood pressure 13080 mmHg and life-style recommendations such as stop smoking and controlled protein and sodium intake
180 patients will be enrolled in the study
Several data are available that proteinuria is an important determinant of progression to ESRD and a risk factor for increased cardiovascular morbidity and mortality Drugs such as Angiotensin-Converting-Enzyme inhibitors ACEi and Angiotensin II receptor antagonists ATA that decrease proteinuria are also reno- and cardio-protective in the long-termThe combination of these drugs may reduce proteinuria more effectively than the two drugs alone Preliminary data are also available that statins in addition to ameliorate the lipid profile may have specific renoprotective properties and combined to ACEi and ATA may synergize their antiproteinuric effects in experimental models of chronic renal diseaseMoreover the addition of statins to antihypertensive treatment with or without inhibitors of the renin-angiotensin system has an additive effect on reducing proteinuria also in humansWhether also in humans combining statins to ACEi and ATA may reduce proteinuria more effectively than ACEi and ATA alone is therefore worth investigating
AIMS Primary
- To assess whether statins combined to ACEi and ATA more effectively than ACEi and ATA alone reduce urinary protein excretion rate in chronic proteinuric nephropathies
Secondary
To assess the effect of statins combined to ACEi and ATA vs the combination of ACEi and ATA alone on other outcome variables including urinary proteincreatinine ratio glomerular filtration rate GFR lipid profile and in a subgroup endothelial function - To evaluate by correlation and multivariate analyses the relationship between baseline follow-up covariates and the above outcome variables in the study group as a whole and within each treatment group
To assess treatment tolerability DESIGN This is be a prospective randomized parallel group study in which following a 2 month Wash-out period from previous treatment if any with ACEi ATA potassium sparing diuretics or statins patients will enter a two-month Run-In phase on renin angiotensin system RAS inhibitor therapy ACE inhibition by benazepril for one month and ACE inhibition plus angiotensin II antagonism by combined treatment with benazepril and valsartan for one further month At completion of the Run-in period and after a baseline evaluation patients will be randomized to a six-month Treatment period with or without fluvastatin Regardless of the randomization group all patients will be offered optimal conservative treatment including optimal blood pressure controlsystolicdiastolic blood pressure 13080 mmHg and life-style recommendations such as stop smoking and controlled protein and sodium intake
180 patients will be enrolled in the study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None