Chronic NephropathyPhase 3ESPLANADENCT00199927
Statins in Proteinuric Nephropathies
A Phase 3 study testing Fluvastatin and standard therapy in people with Chronic Nephropathy and Proteinuria, run by Mario Negri Institute for Pharmacological Research at 16 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 80 years
- Conditions the study is for
- Chronic Nephropathy, Proteinuria, Hypertension
- What is being tested?
- Fluvastatin and standard therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 217 participants
- Where
- 16 sitesItaly
- Study dates
- Mar 2003to Mar 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Italy16 sites
Hospital "S.Marte e S.Venere" - Unit of Nephrology and Dialysis
Acireale, Catania, 95024
Hospital "Santa Maria dell'Annunziata" - Unit of Nephrology
Bagno a Ripoli, Firenze, 50011
Hospital "S.Giacomo Apostolo"
Castelfranco Veneto, Treviso, 31033
Hospital "Vittorio Emanuele II, S. Bambino, Ferrarotto" - Unit of Nephrology and Dialisys
Catania, Catania, 95100
Hospital "Ciaccio" - Unit of Nephrolofy and Dialysis
Catanzaro, Catanzaro, 88100
Hospital "Careggi Monna Tessa" - Unit of Nephrology and Dialysis
Florence, Firenze
Hospital "Santa Maria della Gruccia" - Unit of Nephrology and Dialysis
Montevarchi, Arezzo, 52100
Hospital of Padova - Unit of Nephrology and Dialysis
Padova, Padova, 31033
Hospital "Civico e Benefratelli" - Unit of Nephrology and Hemodialysis
Palermo, Palermo, 90100
Hospital of Parma - Department of Medical Clinic
Parma, Parma, 43100
Clinical Research Center for Rare Diseases
Ranica, Bergamo, 24020
"Ospedali Riuniti" CNR I.B.I.M. - Unit of Nephrology
Reggio Calabria, 89124
Hospital "Casa Sollievo della Sofferenza" - Unit of Nephrology and Dialysis
San Giovanni Rotondo, Foggia, 71013
University of Sassari - Institute of Medical Pathology
Sassari, Sassari, 07100
Hospital "G.Mazzini" - Unit of Nephrology and Dialysis
Teramo, Teramo, 64100
Hospital of Mestre - Unit of Nephrology and Dialysis
Venezia, Venezia, 30174
About this study
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
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.
Read the 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.
- Conditions
- Chronic Nephropathy, Proteinuria, Hypertension
- Being tested
- Fluvastatin, standard therapy
- Medical subject headings
- Proteinuria, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FluvastatinDrug
Starting dose of Fluvastatin of 40 mg/day uptitrated to 80 mg/day
standard therapyDrug
standard therapy
| Study group | Role | What they receive |
|---|---|---|
| standard therapy | Active comparator | Standard therapy Receives: Drug: standard therapy |
| fluvastatin | Active comparator | 40-80 mg/day Receives: Drug: Fluvastatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
24-hour urinary protein excretion rate, at the end of 6 months treatment phase
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startMar 2003
- Primary completionDec 2007
- Study completionMar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic NephropathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 217 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mario Negri Institute for Pharmacological Research
- Sponsor type
- University, hospital or other
- Investigators
- Piero Ruggenenti, MD, Principal investigator, Mario Negri Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00199927
- Sponsor's protocol ID
- ESPLANADE
- Acronym
- ESPLANADE
- Status last verified
- Apr 2010
- First submitted
- 12 Sep 2005
- Last updated
- 28 Apr 2010
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 38018702Ruggenenti 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.
PubMed 20671225
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00199927
- Acronym / sponsor ID
- ESPLANADE / ESPLANADE
- Conditions
- Chronic Nephropathy, Proteinuria, Hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 217 participants (actual)
- Lead sponsor
- Mario Negri Institute for Pharmacological ResearchUniversity, hospital or other
- Study start
- Mar 2003
- Primary completion
- Dec 2007 (actual)
- Study completion
- Mar 2008 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| standard therapy | Active comparator | Drug: standard therapyStandard therapy |
| fluvastatin | Active comparator | Drug: Fluvastatin40-80 mg/day |
Who may qualify
- Ages
- 16 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FluvastatinStarting dose of Fluvastatin of 40 mg/day uptitrated to 80 mg/day | Drug | fluvastatin |
| standard therapystandard therapy | Drug | standard therapy |
Primary outcome
24-hour urinary protein excretion rate, at the end of 6 months treatment phase
Time frame: At 0, 2,3,4,5,6,7,8,9,10 months.
1 secondary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2010.
- Derived from this study: PubMed 38018702Tunnicliffe 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.
- Derived from this study: PubMed 20671225Ruggenenti 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Piero Ruggenenti, MD principal investigator
Mario Negri Institute
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fluvastatin and standard therapy in people with Chronic Nephropathy and Proteinuria, run by Mario Negri Institute for Pharmacological Research at 16 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Apr 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
24-hour urinary protein excretion rate, at the end of 6 months treatment phase (time frame: At 0, 2,3,4,5,6,7,8,9,10 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00199927, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2010.