Platelet Function in Diabetic Patients With and Without Renal Impairment, and the Effects of Lipid Lowering Treatment

Phase 4

Completed

• Conditions: Impaired Renal Function; Diabetes Mellitus
• Interventions: Drug: Ezetimibe

• Registration Number: NCT01035320
• Lead Sponsor: Karolinska Institutet

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.

Study Timeline

• Study Start: 2006-01
• Study First Submitted: 2009-12-17
• Study First Submitted QC: 2009-12-17
• Study First Posted: 2009-12-18
• Primary Completion: 2012-06
• Study Completion: 2012-06
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-25
• Last Update Posted: 2021-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 39

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
simvastatin + ezetimibe	Ezetimibe	Cross-over study with placebo only run-in period. All patients participate in this arm with simvastatin + ezetimibe either as first treatment period (8-10 weeks)or second treatment period (8-10 weeks). The primary comparison is ezetimibe vs. placebo on top of simvastatin. A secondary comparison will be simvastatin vs. placebo run-in.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Department of Medicine, Clinical Pharmacology Unit, Karolinska University Hospital (Solna); 🇸🇪 Stockholm, Sweden