Diabetes and Combined Lipid Therapy Regimen (DIACOR) Study
The primary study hypothesis of this study is to determine whether there is a greater percentage of patients achieving a triglyceride level of <200 mg/dL with the combination of simvastatin 20 mg and fenofibrate 160mg than with either simvastatin 20 mg monotherapy or fenofibrate 160mg monotherapy.
Type II Diabetes Mellitus
Drug: fenofibrate 160 mg and placebo
Drug: simvastatin 20 mg and placebo
Drug: fenofibrate 160 mg and simvastatin 20 mg
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Official Title:||Diabetes and Combined Lipid Therapy Regimen (DIACOR) Study: A Randomized, Double-Blind Study of Simvastatin, Fenofibrate, and Combined Fenofibrate and Simvastatin in Patients With Controlled Type II Diabetics Without Evidence of Coronary Disease|
- percent of patients achieving study goal oftriglycerides <200 mg/dL
- Percent of patients achieving all study goals: LDL-C < 100 mg/dL, HDL-C:40 mg/dL, Triglycerides <200 mg/dL and the Percent of patients achieving non-HDL cholesterol <130 mg/dL
|Study Start Date:||August 2002|
|Estimated Study Completion Date:||September 2006|
Diabetes is a strong risk factor for atherosclerosis and is often characterized by dyslipidemia with hypertriglyceridemia,low high-density lipoprotein (HDL), and modestly elevated low-density lipoprotein (LDL). Both HMG-CoA reductase inhibitors (statins) and fibrates improve lipoprotein metabolism and decrease coronary disease risk. Statins and fibrates affect different aspects of lipoprotein metabolism and each improve lipid metabolism complimentarily. Statins lower total cholesterol and LDL while fibrates decrease triglyceride concentrations and elevateHDL cholesterol. Since individual lipid parameters have been shown to be independent cardiovascular risk factors, it is especially important to target all lipid parameters to levels outlined in treatment guidelines.
The National Cholesterol Education Program Adult Treatment Panel ill (NCEP ill) guidelines have set target therapeutic levels for coronary heart disease (CHD) and CHD risk equivalents (including diabetes).Many patients, however, are not able to achieve optimal levels with a single lipid-controlling agent.
This is particularly evident among diabetics, who often have multiple dyslipidemias and are less likely to achieve effective lipid control.
Several small clinical trials have demonstrated that fibrate and statin dual therapy combine the specific effects of the two drugs by significantlyreducing total and LDL cholesterol while increasing HDL cholesterol, though problems are associated. Previous studies, conducted mainly with a gemfibrozil/cerivastatin combination, showed an increased incidence of side effects (myopathy, hepatotoxicity) and high cost. This problem was again addressed in a small study of74 patients randomized to combined or alternate-day simvastatin and fenofibrate therapy. Surprisingly, in this study, no cases of myopathy were reported, even among patients receiving combined simvastatin and fenofibrate therapy.
The Lipids in Diabetes Study (LDSH Study) examined the fenofibrate and cerivastatin combination in a large-scale trial of 4,000 patients. This study was stopped early because study treatment included cerivastatin, which was withdrawn from the United States market in 2001. Consequently, the results' utility will be limited in the United States.
Additional studies evaluating lipid therapies capable of meeting more aggressive treatment guidelines outlined in NCEP ill, especially among diabetic patients, are required. We propose a twelve-month study of simvastatin, micronized fenofibrate, and combination therapy among patients with controlled Type 2 diabetes mellitus. The primary objectives ofthis study will be to assess the safety and efficacy of combined micronized fenofibrate and simvastatin therapy versus micronized fenofibrate or simvastatin monotherapy. Secondary objectives will include evaluation of combined micronized fenofibrate and simvastatin therapy versus micronized fenofibrate or simvastatin monotherapy on novel lipid parameters and serological markers associated with significantly increased cardiovascular risk. The benefits of the study will be numerous. First, we will be able to detennine the efficacy of each treatment arm in achieving the more aggressive lipid level targets outlined in NCEP ill. Second, this trial, unlike previous studies, will assess the safety and efficacy of each treatment arm specifically among diabetic patients. Third, the length of therapy will allow adequate, yet efficient, evaluation of the tertiary endpoints, which include novel risk factors not previously assessed with combination therapy.
|United States, Utah|
|McKay Dee Hospital|
|Ogden, Utah, United States, 84403|
|Salt Lake City, Utah, United States, 84143|
|Principal Investigator:||Joseph B Muhlestein, MD||Intermountain Health Care, Inc.|