Statins in Proteinuric Nephropathies

NCT00199927 | Completed Phase 3

• 1 other identifier: ESPLANADE
• Study Type: interventional
• Target: 217
• Locations: 1 country
• Sites: 16

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 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.

Conditions

Chronic Nephropathy; Proteinuria; Hypertension

Outcome Measures

Primary Outcomes (1)

• 24-hour urinary protein excretion rate, at the end of 6 months treatment phase

  At 0, 2,3,4,5,6,7,8,9,10 months.

Secondary Outcomes (1)

• Urinary protein/creatinine ratio; glomerular filtration rate (GFR); lipid profile. In a subgroup: renal plasma flow (RPF); filtration fraction albumin; IgG and IgM fractional clearance; insulin sensitivity; urinary endothelin excretion.

Study Arms (2)

standard therapy

ACTIVE COMPARATOR

Standard therapy

Drug: standard therapy

fluvastatin

ACTIVE COMPARATOR

40-80 mg/day

Drug: Fluvastatin

Interventions

Fluvastatin DRUG

Starting dose of Fluvastatin of 40 mg/day uptitrated to 80 mg/day

fluvastatin

standard therapy DRUG

standard therapy

standard therapy

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• age \>16 years
• hypertension, defined as a systolic or diastolic blood pressure \> 140 or 90 mmHg respectively (or less in patients with concomitant antihypertensive therapy)
• creatinine clearance \>20 ml/min/1.73m2 (with variation of less than 30% in the 3 months prior to study entry)
• urinary protein excretion rate persistently \> 1 g/24 hours (average of at least two measurements in two urine collections two weeks apart) without evidence of urinary tract infection or overt heart failure (New York Heart Association class III or more)
• written informed consent

You may not qualify if:

• specific contraindication to statin therapy because of a previous coronary event or serum LDL-cholesterol levels \> 190 mg/dL despite a low cholesterol (\<200 mg/day) diet and a saturated fatty acid in take less than 7% of total calories will not be included
• chronic treatment with corticosteroids, nonsteroidal anti-inflammatory drugs, or immunosuppressive drugs
• acute myocardial infarction or cerebrovascular accident in the six months preceding the study - severe uncontrolled hypertension (diastolic blood pressure \>115 and/or systolic blood pressure \>220 mmHg)
• evidence or suspicion of renovascular disease, obstructive uropathy, type 1 diabetes mellitus, vasculitides, cancer
• elevated serum aminotransferase concentrations - chronic cough
• history of poor tolerance or allergy to ACEi, ATA or statins
• drug or alcohol abuse
• pregnancy, breast feeding and ineffective contraception
• legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the trial.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (16)

Hospital "Santa Maria della Gruccia" - Unit of Nephrology and Dialysis

Montevarchi, Arezzo, 52100, Italy

Location

Clinical Research Center for Rare Diseases

Ranica, Bergamo, 24020, Italy

Location

Hospital "S.Marte e S.Venere" - Unit of Nephrology and Dialysis

Acireale, Catania, 95024, Italy

Location

Hospital "Vittorio Emanuele II, S. Bambino, Ferrarotto" - Unit of Nephrology and Dialisys

Catania, Catania, 95100, Italy

Location

Hospital "Ciaccio" - Unit of Nephrolofy and Dialysis

Catanzaro, Catanzaro, 88100, Italy

Location

Hospital "Santa Maria dell'Annunziata" - Unit of Nephrology

Bagno a Ripoli, Firenze, 50011, Italy

Location

Hospital "Careggi Monna Tessa" - Unit of Nephrology and Dialysis

Florence, Firenze, Italy

Location

Hospital "Casa Sollievo della Sofferenza" - Unit of Nephrology and Dialysis

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Hospital of Padova - Unit of Nephrology and Dialysis

Padua, Padova, 31033, Italy

Location

Hospital "Civico e Benefratelli" - Unit of Nephrology and Hemodialysis

Palermo, Palermo, 90100, Italy

Location

Hospital of Parma - Department of Medical Clinic

Parma, Parma, 43100, Italy

Location

University of Sassari - Institute of Medical Pathology

Sassari, Sassari, 07100, Italy

Location

Hospital "G.Mazzini" - Unit of Nephrology and Dialysis

Teramo, Teramo, 64100, Italy

Location

Hospital "S.Giacomo Apostolo"

Castelfranco Veneto, Treviso, 31033, Italy

Location

Hospital of Mestre - Unit of Nephrology and Dialysis

Venezia, Venezia, 30174, Italy

Location

"Ospedali Riuniti" CNR I.B.I.M. - Unit of Nephrology

Reggio Calabria, 89124, Italy

Location

Related Publications (2)

• Tunnicliffe DJ, Palmer SC, Cashmore BA, Saglimbene VM, Krishnasamy R, Lambert K, Johnson DW, Craig JC, Strippoli GF. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2023 Nov 29;11(11):CD007784. doi: 10.1002/14651858.CD007784.pub3.

  PMID: 38018702 DERIVED

• Ruggenenti P, Perna A, Tonelli M, Loriga G, Motterlini N, Rubis N, Ledda F, Rota S Jr, Satta A, Granata A, Battaglia G, Cambareri F, David S, Gaspari F, Stucchi N, Carminati S, Ene-Iordache B, Cravedi P, Remuzzi G; ESPLANADE Study Group. Effects of add-on fluvastatin therapy in patients with chronic proteinuric nephropathy on dual renin-angiotensin system blockade: the ESPLANADE trial. Clin J Am Soc Nephrol. 2010 Nov;5(11):1928-38. doi: 10.2215/CJN.03380410. Epub 2010 Jul 29.

  PMID: 20671225 DERIVED

MeSH Terms

Conditions

Proteinuria; Hypertension

Interventions

Fluvastatin; Standard of Care

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Piero Ruggenenti, MD

  Mario Negri Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: March 1, 2003
• Primary Completion: December 1, 2007
• Study Completion: March 1, 2008
• Last Updated: April 28, 2010

Record last verified: 2010-04

Locations

IT (16)