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

• ClinicalTrials.gov Identifier: NCT02015988
• Recruitment Status: Unknown
• First Posted: December 19, 2013
• Last Update Posted: August 4, 2016
• Sponsor: Koval' O., MD
• Information provided by (Responsible Party): Koval' O., MD, Dnipropetrovsk State Medical Academy

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Acute Coronary Syndrome; Diabetes Mellitus, Type 2; Hypertriglyceridemia	Drug: Fenofibrate; Drug: Simvastatin	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: January 2014
• Estimated Primary Completion Date: September 2016
• Estimated Study Completion Date: May 2017

Arms and Interventions

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 Name: Tricor; Drug: Simvastatin; Other Name: Zocor-forte
Active Comparator: Simvastatin; Simvastatin 40 mg once daily orally for 52 weeks (1 year)	Drug: Simvastatin; Other Name: Zocor-forte

Outcome Measures

Primary Outcome Measures :

1. Percentage change from baseline in triglycerides (TG) at week 12 [ Time Frame: Baseline, Week 12 ]

Secondary Outcome Measures :

1. Percentage of patients who achieved non-High-Density Lipoprotein-Cholesterol (non-HDL-C) level less than 2,6 mmol/l at week 12 [ Time Frame: Week 12 ]
2. Percentage changes from baseline in apoB/apoA1 ratio at week 12 [ Time Frame: Baseline, Week 12 ]
3. Percentage changes from baseline in non-High-Density Lipoprotein-Cholesterol (non-HDL-C) at week 12 [ Time Frame: Baseline, Week 12 ]
4. Percentage changes from baseline in High-Density Lipoprotein-Cholesterol (HDL-C) at week 12 [ Time Frame: Baseline, Week 12 ]
5. Percentage changes from baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) at week 12 [ Time Frame: Baseline, Week 12 ]
6. Percentage changes from baseline in uric acid at week 12 [ Time Frame: Baseline, Week 12 ]
7. Percentage of patients who achieved non-High-Density Lipoprotein-Cholesterol (non-HDL-C) level less than 2,6 mmol/l at week 52 [ Time Frame: Week 52 ]
8. Percentage changes from baseline in apoB/apoA1 ratio at week 52 [ Time Frame: Baseline, Week 52 ]
9. Percentage changes from baseline in non-High-Density Lipoprotein-Cholesterol (non-HDL-C) at week 52 [ Time Frame: Baseline, Week 52 ]
10. Percentage changes from baseline in High-Density Lipoprotein-Cholesterol (HDL-C) at week 52 [ Time Frame: Baseline, Week 52 ]
11. Percentage changes from baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) at week 52 [ Time Frame: Baseline, Week 52 ]
12. Percentage changes from baseline in uric acid at week 52 [ Time Frame: Baseline, Week 52 ]

Other Outcome Measures:

1. Number of adverse events (AE) caused discontinuations of investigational products [ Time Frame: Up to 52 week ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Ukraine

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

Dnipropetrovsk, Ukraine

Sponsors and Collaborators

Koval' O., MD

Investigators

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

More Information

• Responsible Party: Koval' O., MD, PhD, Professor, Dnipropetrovsk State Medical Academy
• ClinicalTrials.gov Identifier: NCT02015988 History of Changes
• Other Study ID Numbers: A14-284
• First Posted: December 19, 2013
• Last Update Posted: August 4, 2016
• Last Verified: August 2016

Keywords provided by Koval' O., MD, Dnipropetrovsk State Medical Academy:

Acute coronary syndrome; Diabetes Mellitus, Type 2; Hypertriglyceridemia; Simvastatin; Fenofibrate

Additional relevant MeSH terms:

Acute Coronary Syndrome; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypertriglyceridemia; Syndrome; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Disease; Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Simvastatin; Fenofibrate; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors