Ezetimibe and Simvastatin in Dyslipidemia of Diabetes
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|ClinicalTrials.gov Identifier: NCT00157482|
Recruitment Status : Completed
First Posted : September 12, 2005
Last Update Posted : February 13, 2007
|First Submitted Date ICMJE||September 8, 2005|
|First Posted Date ICMJE||September 12, 2005|
|Last Update Posted Date||February 13, 2007|
|Study Start Date ICMJE||January 2005|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||LDL-cholesterol, at 16 weeks of treatment. LDL-cholesterol is measured at -4, 0, 8, 12 and 16 weeks.|
|Original Primary Outcome Measures ICMJE
||LDL-cholesterol, at 16 weeks of treatment.LDL-cholesterol is measured at -4, 0, 8, 12 and 16 weeks|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||Ezetimibe and Simvastatin in Dyslipidemia of Diabetes|
|Official Title ICMJE||A Randomized, Prospective, Double-Blind Study to Evaluate the Effects on Lipid Profile of Combined Ezetimibe and Simvastatin Therapy as Compared to Simvastatin Alone in People With Type 2 Diabetes|
Diabetes mellitus is becoming a global epidemic burden. Its chronic cardiovascular complications, myocardial infarction and stroke, are the main causes of death in diabetic patients. It was found that low density lipoprotein (LDL) cholesterol concentration is related to the increased coronary disease risk that could be successfully reduced by cholesterol-lowering therapy. Furthermore, preliminary evidence suggests that ameliorating dyslipidemia may be renoprotective in diabetic patients with proteinuria.
Ezetimibe is the first selective inhibitor of cholesterol absorption and it has demonstrated a high efficacy in lowering cholesterol concentration and an excellent safety profile. Preliminary data suggest that ezetimibe, combined with a drug that blocks the cholesterol synthesis (statins), could be even more effective in decreasing cholesterol concentration. The aim of this study is to evaluate whether ezetimibe-simvastatin combined therapy is superior to simvastatin monotherapy in ameliorating the lipid profile and albuminuria in type 2 diabetic patients.
Diabetes mellitus contributes substantially to the global burden of disease, with an estimated 150 million people affected worldwide and its prevalence is expected to double by 2025. Myocardial infarction and stroke are common causes of major morbidity in people with diabetes, most of whose deaths are attributed to cardiovascular causes. Recent findings provide definitive evidences that cholesterol-lowering therapy can produce substantial reductions in the risk of heart attacks, stroke and revascularizations in diabetic patients even if they do not have high blood cholesterol concentrations.
Also preliminary evidence is available that ameliorating dyslipidemia may be renoprotective in diabetic patients with proteinuria.
Ezetimibe is the first member of a class of highly selective cholesterol absorption inhibitors that effectively and potently prevents the absorption of cholesterol by inhibiting the passage of biliary and dietary cholesterol across the wall of the small intestine, without affecting absorption of other fat-soluble nutrients.
Many pre-clinical models have demonstrated the lipid-lowering and anti-atherosclerotic properties of ezetimibe as a single agent, and showed its synergistic effect in combination with HMGCoA reductase inhibitors (statins).
Phase I/II studies on patients with hypercholesterolemia have explored the safety and efficacy of ezetimibe monotherapy and co-administration with simvastatin. In these studies, combined therapy was safely and invariably more effective than single therapy in ameliorating the lipid profile.
Ezetimibe had an excellent safety profile in standard toxicity studies in pre-clinical models. Clinical studies in patients with primary hyperlipidemia have also indicated that monotherapy with ezetimibe and coadministration with a statin were both well tolerated. Whether ezetimibe-simvastatin combined therapy more effectively than simvastatin monotherapy ameliorates the lipid profile and albuminuria in people with diabetes is worth investigating. Evidence of a superior efficacy of ezetimibe-simvastatin would provide the rationale for a prospective trial aimed to explore the possibility of a superior cardioprotective and renoprotective effect of the combined therapy.
To explore the hypothesis that ameliorating dyslipidemia therapy may also result in a reduction of urinary albumin excretion rate.
This will be a randomized, prospective, double-blind, parallel group study. Following a 4-week wash-out period from previous lipid-lowering therapy (if any) with HMGCoA reductase inhibitors or any other kinds of lipid-lowering drugs, patients will enter a two-month run-in phase with simvastatin 40mg per day. At completion of the run-in period, patients will be randomly allocated into two double-blind treatment arms, ezetimibe 10mg + simvastatin 40mg per day or placebo + simvastatin 40mg per day for a two-month treatment period.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 2|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Diagnostic
|Condition ICMJE||Type 2 Diabetes|
|Study Arms ICMJE||Not Provided|
|Publications *||Ruggenenti P, Cattaneo D, Rota S, Iliev I, Parvanova A, Diadei O, Ene-Iordache B, Ferrari S, Bossi AC, Trevisan R, Belviso A, Remuzzi G; Ezetimibe and Simvastatin in Dyslipidemia of Diabetes (ESD) Study Group. Effects of combined ezetimibe and simvastatin therapy as compared with simvastatin alone in patients with type 2 diabetes: a prospective randomized double-blind clinical trial. Diabetes Care. 2010 Sep;33(9):1954-6. doi: 10.2337/dc10-0320. Epub 2010 Jun 21.|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||December 2006|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years to 70 Years (Adult, Older Adult)|
|Accepts Healthy Volunteers ICMJE||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Italy|
|Removed Location Countries|
|NCT Number ICMJE||NCT00157482|
|Other Study ID Numbers ICMJE||ESD|
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Mario Negri Institute for Pharmacological Research|
|Collaborators ICMJE||Not Provided|
|PRS Account||Mario Negri Institute for Pharmacological Research|
|Verification Date||December 2006|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP