Ezetimibe/Simvastatin Combination in Proteinuric Nephropathy (VICTORY)

April 27, 2009 updated by: Azienda Ospedaliero Universitaria di Sassari

The Metabolic and Anti-Inflammatory Effects of Combined Ezetimibe and Simvastin Therapy, as Compared to Simvastatin Alone, in Patients With Chronic Proteinuric Nephropathy

The purpose of this study is to determine whether, in patients with chronic proteinuric nephropathy and dyslipidemia, ezetimibe-simvastatin combined therapy is more effective than statin alone to achieve the optimum lipid control, and if this translates to an improvement of the markers of vascular damage. Thirty hypertensive patients in stable therapy with RAS inhibitors, with low-density lipoprotein (LDL) cholesterol superior to 100 mg/ml, are treated with three different hypolipidemic regimens: Simvastatin alone (40 mg/day) or ezetimibe/simvastatin combined therapy (10/20 or 10/40 mg/day).

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Patients with chronic kidney disease (CKD) have an increased incidence of cardiovascular morbidity and mortality. Presence of hypertension, lipid abnormalities and inflammation each contribute to increased cardiovascular risk. Therefore blood pressure control slows the progression of CKD towards End Stage Renal Failure (ESRF) improving clinical outcome.

Instead the contribution of lipid abnormalities is still not completely understood, mainly because dyslipidemia interferes with a number of non-traditional cardiovascular risk factors, particularly the activated acute-phase response.

In proteinuric patients, dyslipidemia has a highly atherogenic profile, with increased total and low-density lipoprotein (LDL) cholesterol, triglyceride, and lipoprotein(a) serum levels, as well as decreased HDL cholesterol. Numerous studies have indicated that treatment of dyslipidemia with a statin decreases cardiovascular morbidity and mortality. Experimental and clinical evidences show that statin, in addition to ameliorate lipid profile, may have specific renoprotective properties and, combined to Renin-Angiotensin System (RAS) inhibitor therapy, may synergize their antiproteinuric effects.

Preliminary data are also available data that the combination of statin to ezetimibe (EZE), a cholesterol absorption inhibitor, produces an additional decrease in LDL cholesterol and C-reactive protein levels, over that achieved with statin monotherapy.

Thus, adding the potential antinflammatory effect to hypolipidemic efficacy, combined therapy may expand the renal and cardioprotective potentiality. It may also permit a reduction of statin therapeutic dose improving safety profile. Therefore EZE-statin combination therapy may be an effective therapeutic option to statin alone in patients with high cardiovascular risk, such as chronic proteinuric patients.

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Sassari, Italy, 07100
        • Istituto di Patologia Medica - Azienda Ospedaliero Universitaria

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age >18 years
  • LDL-cholesterol > 100 mg/dl (without concomitant hypolipidemic drugs) in patients whit high cardiovarscular risk for the concomitant presence of:
  • proteinuric chronic nephropathy defined as creatinine clearance > 20 ml/min/1,73 m2 combined to a urinary protein excretion rate > 0,3 g/24h, without evidence of urinary tract infection or overt heart failure (New York Heart Association class III or more)
  • hypertension defined as a systolic or diastolic blood pressure > 140 or 90 mmHg respectively (or less in patients with concomitant antihypertensive therapy)

Exclusion Criteria:

  • previous or concomitant treatment with steroids, anti-inflammatory and immunosuppressive agents
  • evidence or suspicion of renovascular disease, obstructive uropathy, type I diabetes mellitus, vasculitides, history of poor tolerance or allergy to ACEi and ATA, statin or EZE, drug abuse or pregnancy
  • inability to fully understand the purposes/risks of the study and to provide a written informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
hypolipidemic treatment
Drug: simvastatin
simvasatin therapy alone at the dose of 40 mg/day
Sham Comparator: 2
hypolipidemic treatment
Drug: EZE/simvastatin
EZE/simvastatin combined therapy at the dose of 10/20 mg/day
Drug: EZE/simvastatin
EZE/simvastatin combined therapy at the dose of 10/40 mg/day
Sham Comparator: 3
hypolipidemic treatment
Drug: EZE/simvastatin
EZE/simvastatin combined therapy at the dose of 10/20 mg/day
Drug: EZE/simvastatin
EZE/simvastatin combined therapy at the dose of 10/40 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To assess whether EZE-statin combined therapy is more effective than statin alone to achieve the optimum lipid control (LDL-cholesterol < 70 mg/dl) in chronic proteinuric nephropathy.
Time Frame: at baseline and every 4 months after therapy start
at baseline and every 4 months after therapy start

Secondary Outcome Measures

Outcome Measure
Time Frame
To assess the effect of EZE-statin combined therapy vs statin monotherapy on other outcome variables including: - renal parameters - inflammatory status - markers of endothelial dysfunction
Time Frame: after one year observational period
after one year observational period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Ospedaliero Universitaria di Sassari

Investigators

  • Principal Investigator: Andrea E Satta, MD, Istituto di Patologia Medica -Azienda Ospedaliero Universitaria di Sassari

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (Anticipated)

July 1, 2009

Study Completion (Anticipated)

July 1, 2009

Study Registration Dates

First Submitted

March 12, 2009

First Submitted That Met QC Criteria

March 12, 2009

First Posted (Estimate)

March 13, 2009

Study Record Updates

Last Update Posted (Estimate)

April 28, 2009

Last Update Submitted That Met QC Criteria

April 27, 2009

Last Verified

April 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AOUSS-Nefologia-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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