Clinical trial NCT02015988: Simvastatin and Fenofibrate vs Simvastatin Alone in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome
Official title: Effectiveness and Tolerability of Early Initiation of Combined Lipid -Lowering Therapy Included Simvastatin and Fenofibrate vs Simvastatin Alone in Patients With Type 2 Diabetes Mellitus, Hypertriglyceridemia and Acute Coronary Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Coronary Syndrome
Diabetes Mellitus, Type 2
Hypertriglyceridemia
Keywords: Acute coronary syndrome
Diabetes Mellitus, Type 2
Hypertriglyceridemia
Simvastatin
Fenofibrate
Lead sponsor: Dnipropetrovsk State Medical Academy
Sponsor class: OTHER
First posted: 2013-12-19
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To test the hypothesis that early (within 5-21 days after index event) administration of combined lipid-lowering therapy in extremely high risk population of patients with type 2 diabetes mellitus (T2DM) and hypertriglyceridemia (HTG) who experienced acute coronary syndrome (ACS) will be effective and well tolerated in achievement of contemporary strict requirements for triglyceride (TG) levels as an independent risk factor in the case of HTG with diabetes.

Detailed description: The primary objective of this parallel group study is to demonstrate that the combined therapy of simvastatin and fenofibrate is superior compared to monotherapy with simvastatin based on the comparisons of change of TG levels after 12 weeks of treatment compared to baseline.

Secondary objectives are to compare both treatment alternatives the combination therapy of simvastatin and fenofibrate to simvastatin monotherapy with respect to achievement the European Society of Cardiology 2011 (ESC 2011) non-HDL-C target (less than 2,6 mmol/l), change of apolipoprotein B/apolipoprotein A1 (apoB/apoA1) ratio, High-Density Lipoprotein-Cholesterol (HDL-C), Low-Density Lipoprotein-Cholesterol (LDL-C) and Uric Acid (UA) after 12 weeks and 52 weeks (1 year) of treatment compared to baseline.

Eligibility criteria: Inclusion Criteria:

* Type 2 Diabetes Mellitus
* Fasting triglycerides ≥ 1,7 mmol/l
* Acute coronary syndrome at least before 5 and maximum 21 days before the inclusion
* If previously treated with statin therapy, the dose should be equivalent to 40 mg of simvastatin at inclusion
* In case of previous statin therapy, last LDL-C measurement before event should be ≤ 2,6 mmol/l
* Written informed consent obtained

Exclusion Criteria:

* Heart failure IV class (NYHA)
* Acute decompensated heart failure
* Life expectancy no more than 1 year
* Chronic kidney disease (CKD) with Estimated glomerular filtration rate (eGFR) \< 30 ml/min/1.73m2
* Severe chronic liver diseases with Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) \> 3 Upper Limit of Normal (ULN)
* Known gallbladder disease, including cholecystolithiasis
* Creatinphosphokinase (CPK) \> 5 ULN at baseline
* Chronic or acute pancreatitis with the exception of acute pancreatitis due to severe hypertriglyceridemia
* Known photoallergy or phototoxic reaction during treatment with fibrates or ketoprofen,
* Known allergy to peanut or arachis oil or soya lecithin or related products
* Hypersensitivity to simvastatin or fenofibrate or to any of the excipients of the investigational drugs
* Concomitant administration of potent cytochrome P450 isoenzyme 3A4 inhibitors (e.g. itraconazole, ketoconazole, fluconazole, posaconazole, Human Immunodeficiency Virus (HIV) protease inhibitors (e.g. nelfinavir), erythromycin, clarithromycin, telithromycin and nefazodone)
* Pregnancy and lactation

Primary outcomes:
measure: Percentage change from baseline in triglycerides (TG) at week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Percentage of patients who achieved non-High-Density Lipoprotein-Cholesterol (non-HDL-C) level less than 2,6 mmol/l at week 12
timeFrame: Week 12
measure: Percentage changes from baseline in apoB/apoA1 ratio at week 12
timeFrame: Baseline, Week 12
measure: Percentage changes from baseline in non-High-Density Lipoprotein-Cholesterol (non-HDL-C) at week 12
timeFrame: Baseline, Week 12
measure: Percentage changes from baseline in High-Density Lipoprotein-Cholesterol (HDL-C) at week 12
timeFrame: Baseline, Week 12
measure: Percentage changes from baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) at week 12
timeFrame: Baseline, Week 12
measure: Percentage changes from baseline in uric acid at week 12
timeFrame: Baseline, Week 12
measure: Percentage of patients who achieved non-High-Density Lipoprotein-Cholesterol (non-HDL-C) level less than 2,6 mmol/l at week 52
timeFrame: Week 52
measure: Percentage changes from baseline in apoB/apoA1 ratio at week 52
timeFrame: Baseline, Week 52
measure: Percentage changes from baseline in non-High-Density Lipoprotein-Cholesterol (non-HDL-C) at week 52
timeFrame: Baseline, Week 52
measure: Percentage changes from baseline in High-Density Lipoprotein-Cholesterol (HDL-C) at week 52
timeFrame: Baseline, Week 52
measure: Percentage changes from baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) at week 52
timeFrame: Baseline, Week 52
measure: Percentage changes from baseline in uric acid at week 52
timeFrame: Baseline, Week 52
Other outcomes:
measure: Number of adverse events (AE) caused discontinuations of investigational products
timeFrame: Up to 52 week
Locations:
city: Dnipropetrovsk
country: Ukraine
facility: State Institution "Dnipropetrovsk Medical Academy of Health Ministry of Ukraine"
Study officials:
affiliation: State Institution "Dnipropetrovsk Medical Academy of Health Ministry of Ukraine"
name: Olena A Koval', MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: