Diabetes Mellitus, Impaired Renal Function
Conditions
Brief summary
The purpose of this study is compare the effects of simvastatin+ezetimibe with those of simvastatin alone on platelet activity, platelet-leukocyte interactions and inflammatory variables in diabetic patients with or without impaired renal function.
Detailed description
A detailed study protocol is available.
Interventions
DRUGEzetimibe
After a placebo only run-in period patients (two groups) are treated with simvastatin + ezetimibe and simvastatin + placebo in a cross-over trial. Ezetimibe effects on top of simvastatin will be evaluated as the primary aim; simvastatin effects compared to run-in on placebo will be evaluated as a secondary aim.
Sponsors
Danderyd Hospital
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diabetes mellitus type 1 or type 2 * With or without established microalbuminuria (albumin-to-creatinine ratio (ACR)2,5-25 mg/mmol for men, and 3,5-25 mg/mmol for women, according to ISH and ESC recommended criteria) * Glomerular filtration rate (GFR) between 15-60 ml/min/1.73m2 (measured the last 6 months) or GFR \>75ml/min/1.73m2. The abbreviated Modification of Diet in Renal Disease (MDRD) equation will be used to calculate GFR. * Age 18-80 years
Exclusion criteria
* Definite history of myocardial infarction, coronary revascularisation procedure or stroke. (i.e, a strong clinical indication for statin treatment) * Functioning renal transplant, or living donor-related transplant planned. * Patients on dialysis. * Poor metabolic control, i.e HbA1c \> 9% * Definite history of chronic liver disease, or abnormal liver function (i.e ALT \>1,5 x ULN or, if ALT not available, AST \> 1,5 x ULN). * Evidence of active inflammatory muscle disease (e.g dermatomyositis, polymyositis), or CK\>3 x ULN; * Definite previous adverse reaction to a statin or to ezetimibe * Definite previous adverse reaction to acetylsalicylic acid. * Definite previous adverse reaction to an ACE-inhibitor. * Need for concomitant treatment with a strong inhibitor of CYP3A4, such as itrokonazole, ketokonazole, erythromycin, clarithromycin, HIV-protease inhibitors or nefazodone (i.e. agents that may markedly elevate simvastatin levels).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Compare the effects of simvastatin + ezetimibe with those of simvastatin alone, on thrombogenic mechanisms, in patients with diabetes mellitus type 2. | 6 weeks, 14-18 weeks, 22-24 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Compare effects of simvastatin alone with those of placebo on thrombogenic mechanisms. Compare the effects of simvast. + ezetim. with those of simvast. alone on inflammatory variables. Assess how the treatment effect relate to renal function. | 6 weeks, 14-18 weeks, 22-24 weeks |
Countries
Sweden
Outcome results
None listed