Ignite Creation Date:
2024-05-05 @ 11:51 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00157482
Status:
COMPLETED
Last Update Posted:
2007-02-13
First Post:
2005-09-08
Brief Title:
Ezetimibe and Simvastatin in Dyslipidemia of Diabetes
Sponsor:
Mario Negri Institute for Pharmacological Research
Organization:
Mario Negri Institute for Pharmacological Research
Study Overview
Official Title:
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
Status:
COMPLETED
Status Verified Date:
2006-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
Detailed Description:
INTRODUCTION
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 III 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
AIM
Primary
To compare the effect of ezetimibe-simvastatin combination 10-40mgday and simvastatin 40mgday alone on LDL-cholesterol concentrations in type 2 diabetic patients with basal total cholesterol 135mgdl andor concomitant lipid lowering therapy with HMGCoA reductase inhibitors
Secondary
To compare the effect of the above treatments on total cholesterol apolipoprotein A1 and B lipoprotein a and triglyceride concentrations
To evaluate the safety profile of these two treatments
Explorative
To explore the hypothesis that ameliorating dyslipidemia therapy may also result in a reduction of urinary albumin excretion rate
DESIGN
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
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 III 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
AIM
Primary
To compare the effect of ezetimibe-simvastatin combination 10-40mgday and simvastatin 40mgday alone on LDL-cholesterol concentrations in type 2 diabetic patients with basal total cholesterol 135mgdl andor concomitant lipid lowering therapy with HMGCoA reductase inhibitors
Secondary
To compare the effect of the above treatments on total cholesterol apolipoprotein A1 and B lipoprotein a and triglyceride concentrations
To evaluate the safety profile of these two treatments
Explorative
To explore the hypothesis that ameliorating dyslipidemia therapy may also result in a reduction of urinary albumin excretion rate
DESIGN
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None