Simvastatin and Fenofibrate vs Simvastatin Alone in Patients With Type 2 Diabetes Mellitus and Acute Coronary Syndrome

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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 2; Acute Coronary Syndrome; Hypertriglyceridemia
• Intervention / Treatment: Drug: Fenofibrate; Drug: Simvastatin

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.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Ukraine
  • Dnipropetrovsk, Ukraine
    • State Institution "Dnipropetrovsk Medical Academy of Health Ministry of Ukraine"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Simvastatin and Fenofibrate; Simvastatin 40 mg once daily and fenofibrate 145 mg once daily orally for 52 weeks (1 year)	Drug: Fenofibrate; Other Names: Tricor; Drug: Simvastatin; Other Names: Zocor-forte
ACTIVE_COMPARATOR: Simvastatin; Simvastatin 40 mg once daily orally for 52 weeks (1 year)	Drug: Simvastatin; Other Names: Zocor-forte

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage change from baseline in triglycerides (TG) at week 12	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients who achieved non-High-Density Lipoprotein-Cholesterol (non-HDL-C) level less than 2,6 mmol/l at week 12	Week 12
Percentage changes from baseline in apoB/apoA1 ratio at week 12	Baseline, Week 12
Percentage changes from baseline in non-High-Density Lipoprotein-Cholesterol (non-HDL-C) at week 12	Baseline, Week 12
Percentage changes from baseline in High-Density Lipoprotein-Cholesterol (HDL-C) at week 12	Baseline, Week 12
Percentage changes from baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) at week 12	Baseline, Week 12
Percentage changes from baseline in uric acid at week 12	Baseline, Week 12
Percentage of patients who achieved non-High-Density Lipoprotein-Cholesterol (non-HDL-C) level less than 2,6 mmol/l at week 52	Week 52
Percentage changes from baseline in apoB/apoA1 ratio at week 52	Baseline, Week 52
Percentage changes from baseline in non-High-Density Lipoprotein-Cholesterol (non-HDL-C) at week 52	Baseline, Week 52
Percentage changes from baseline in High-Density Lipoprotein-Cholesterol (HDL-C) at week 52	Baseline, Week 52
Percentage changes from baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) at week 52	Baseline, Week 52
Percentage changes from baseline in uric acid at week 52	Baseline, Week 52

Other Outcome Measures

Outcome Measure	Time Frame
Number of adverse events (AE) caused discontinuations of investigational products	Up to 52 week

Collaborators and Investigators

• Sponsor: Koval' O., MD
• Investigators: Principal Investigator: Olena A Koval', MD, PhD, State Institution "Dnipropetrovsk Medical Academy of Health Ministry of Ukraine"

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ANTICIPATED): September 1, 2016
• Study Completion (ANTICIPATED): May 1, 2017

Study Registration Dates

• First Submitted: December 14, 2013
• First Submitted That Met QC Criteria: December 14, 2013
• First Posted (ESTIMATE): December 19, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): August 4, 2016
• Last Update Submitted That Met QC Criteria: August 3, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Acute coronary syndrome; Diabetes Mellitus, Type 2; Simvastatin; Fenofibrate; Hypertriglyceridemia
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Disease; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Diabetes Mellitus; Diabetes Mellitus, Type 2; Syndrome; Acute Coronary Syndrome; Hypertriglyceridemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Fenofibrate
• Other Study ID Numbers: A14-284