Statins in Proteinuric Nephropathies
Condition: Chronic Nephropathy; Proteinuria; Hypertension
MeSH terms: Kidney Diseases; Proteinuria
Study type: Interventional
Phase: Phase 3

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 statins,in 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 mg/day) treatment YES or NO.Twenty
      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-term.The
      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 disease.Moreover, 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
      humans.Whether 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 protein/creatinine 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 control(systolic/diastolic blood pressure <130/80 mmHg)
           and life-style recommendations such as stop smoking and controlled protein and sodium
           intake.

           180 patients will be enrolled in the study.
    

Intervention name(s): Fluvastatin; standard therapy
Intervention type(s): Drug; Drug
Intervention description(s): Starting dose of Fluvastatin of 40 mg/day uptitrated to 80 mg/day; standard therapy
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment