Effects of Combined Therapy With Statin Plus Fenofibrate on Coronary Atherosclerotic Plaque Compared With Statin Alone

The Comparative Analysis of the Effects on Plaque Volume and Tissue Characteristics Between Combined Therapy With STAatin Plus FENOfibrate and Statin Alone in Mild to Moderate, Non- Intervened Coronary Artery Stenosis (STAFENO Trial)

The purpose of this study is to determine effects of combination therapy with rosuvastatin and fenofibrate on atheromatous plaques and its tissue characteristics of de novo coronary lesions with intermediate stenosis in patient with coronary artery disease, compared with rosuvastatin alone therapy.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Rosuvastatin and fenofibrate; Drug: Rosuvastatin alone

Detailed Description

Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. In the past few decades, optimal pharmacological therapies with statins targeting LDL-cholesterol substantially reduce the risks of cardiovascular disease. However, the residual cardiovascular risk is still high, requiring need for additional preventive therapies to achieve even greater risk reduction.

Recent meta-analysis demonstrated fibrates can reduce the risk of coronary events and might have a role in patients with high cardiovascular risks or combined dyslipidemia. Likewise, fenofibrate had a possible benefit for patients with high triglyceride level and low HDL-cholesterol level in the post-hoc analysis of ACCORD or FIELD trials.

Thus, investigators tried to determine effects of combination therapy with rosuvastatin and fenofibrate on atheromatous plaques and its tissue characteristics of de novo coronary lesions with intermediate stenosis in patient with coronary artery disease, compared with rosuvastatin alone therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 106
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daejeon, Korea, Republic of
    • Not yet recruiting
    • Konyang University Hospital
    • Contact: Jang Ho Bae, MD
    • Principal Investigator: Jang Ho Bae, MD
  • Gwangju, Korea, Republic of
    • Recruiting
    • Chonnam National University Medical School and Hospital
    • Contact: Young-joon Hong, MD
    • Principal Investigator: Young-joon Hong, MD
  • Ilsan, Korea, Republic of
    • Recruiting
    • Inje University IlsanPaik Hospital
    • Contact: Sung Yoon Lee, MD
    • Principal Investigator: Sung Yoon Lee, MD
  • Incheon, Korea, Republic of, 405-760
    • Recruiting
    • Gachon University Gil Medical Center
    • Contact: Seung Hwan Han, MD, PhD; Phone Number: 82-32-460-3054; Email: shhan@gilhospital.com
    • Principal Investigator: Seung Hwan Han, MD
  • Seoul, Korea, Republic of
    • Recruiting
    • Chung-Ang University Hospital
    • Contact: Sang-wook Kim, MD
    • Principal Investigator: Sang-wook Kim, MD
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Seoul National Univesity Boramae Medical Center
    • Contact: Sang Hyun Kim, MD
    • Principal Investigator: Sang Hyun Kim, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with coronary artery disease who were 20 years of age or older and needed coronary angiography
• Intermediate coronary artery stenosis (diameter stenosis ≥30% to ≤60% by visual estimation, diameter ≥2.0 mm to ≤4.0 mm, de novo lesion in native coronary artery) in which virtual histology-intravascular ultrasound (VH-IVUS) could be feasible

• Combined dyslipidemia

  • Stain-naive patients - LDL-cholesterol ≥70 mg/dL and non-HDL-cholesterol ≥130 mg/dL
  • Patients taking statin within 2 weeks - LDL-cholesterol < 100 mg/dL and non-HDL-cholesterol ≥100 mg/dL
• Patients who gave written informed consent

Exclusion Criteria:

• Diabetic patients
• Cardiogenic shock
• Heart failure with symptoms of New York Heart Association class III/IV or left ventricular ejection fraction <35%
• Renal dysfunction (creatinine level ≥1.7 mg/dL or dependence of dialysis
• Hepatic dysfunction (transaminase level > 3 times of normal within limit)
• Pregnancy or breast-feeding women
• Familial hypercholesterolemia
• Hypertriglyceridemia (triglyceride level >500 mg/dL)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin and fenofibrate; Combination therapy: rosuvastatin 10 mg and fenofibrate 160 mg per day	Drug: Rosuvastatin and fenofibrate; Combination therapy: rosuvastatin 10 mg and fenofibrate 160 mg per day; Other Names: Combination therapy with rosuvastatin and fenofibrate
Active Comparator: Rosuvastatin alone; Rosuvastatin 10 mg per day	Drug: Rosuvastatin alone; Rosuvastatin 10mg per day; Other Names: Rosuvastatin alone therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent and Absolute changes of Necrotic Core volume in non-culprit intermediate lesions	Percent and Absolute changes of Necrotic Core volume in non-culprit intermediate lesions by VH-IVUS	After 12±2 months treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent and Absolute changes of area of necrotic core, dense calcium, fibrous plaque in non-culprit intermediate lesions	Percent and Absolute changes of area of necrotic core, dense calcium, fibrous plaque in non-culprit intermediate lesions by VH-IVUS	After 12±2 months treatment
Presence of thin-cap fibroatheroma	change of plaque phenotype by VH-IVUS	After 12±2 months treatment
Absolute and percent changes of volume/area of external elastic membrane, lumen and plaque volume	Absolute and percent changes of volume/area of external elastic membrane, lumen and plaque volume by VH-IVUS	After 12±2 months treatment
Remodeling index	Remodeling index by VH-IVUS	After 12±2 months treatment
Major adverse cardiovascular events (MACE)	The composites of all-cause death, non-fatal myocardial infarction, stroke, culprit lesion revascularization, or non-culprit lesion revascularization	After 12 months treatment
Adverse drug events	Adverse drug events related by study drugs	After 12±2 months treatment
Creatine phosphokinase	measurement of muscular side effects related by study drugs	After 12±2 months treatment

Collaborators and Investigators

• Sponsor: Gachon University Gil Medical Center
• Collaborators: Daewoong Pharmaceutical Co. LTD.
• Investigators: Principal Investigator: Seung Hwan Han, MD, Gachon University Gil Medical Center

Publications and helpful links

General Publications

• Kwon TG, Jang AY, Kim SW, Hong YJ, Bae JH, Lee SY, Kim SH, Han SH. Design and rationale of a randomized control trial testing the effectiveness of combined therapy with STAtin plus FENOfibrate and statin alone in non-diabetic, combined dyslipidemia patients with non-intervened intermediate coronary artery disease - STAFENO study. Trials. 2020 Apr 22;21(1):353. doi: 10.1186/s13063-020-04291-5.

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: September 2, 2014
• First Submitted That Met QC Criteria: September 2, 2014
• First Posted (Estimate): September 5, 2014

Study Record Updates

• Last Update Posted (Actual): May 15, 2019
• Last Update Submitted That Met QC Criteria: May 12, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Coronary artery disease; Atherosclerotic plaque; Rosuvastatin; Fenofibrate; Virtual histology intravascular ultrasound; Plaque composition
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Fenofibrate
• Other Study ID Numbers: STAFENO