Efficacy and Safety of Combination Therapy of Moderate-intensity Statin and Ezetimibe Compared to High-intensity Statin

Phase 4

Completed

• Conditions: Cardiovascular Diseases
• Interventions: Drug: Efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin

• Registration Number: NCT04080310
• Lead Sponsor: Seoul National University Bundang Hospital

Brief Summary

This study is a multicenter, randomized, open-label, parallel, phase IV trial.

The purpose of this study efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin.

Detailed Description

The study is planned to include 272 patients with a clinical atherosclerotic cardiovascular disease requiring optimal statin therapy.

After enrollment, subjects are randomized into two groups in a 1:1 manner. The combination therapy group will receive a single-pill combination of rosuvastatin 10 mg and ezetimibe 10 mg once daily.

The subjects in the intensive statin group will receive rosuvastatin 20 mg once daily.

Subjects will visit at weeks 12 and 24 to identify medication adherence and clinical side effects.

The primary endpoint of this study is a % change of low-density lipoprotein cholesterol at 12 weeks.

Study Timeline

• Study Start: 2018-03-15
• Primary Completion: 2019-06-15
• Study First Submitted: 2019-08-28
• Study First Submitted QC: 2019-09-03
• Study First Posted: 2019-09-06
• Study Completion: 2019-09-17
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-19
• Last Update Posted: 2020-03-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 270

Inclusion Criteria

1. Aged between 19 and 75 years

2. Presence of atherosclerotic cardiovascular disease Coronary artery disease

   • History of acute coronary syndrome
   • Stable or unstable angina
   • History of coronary revascularization Stroke or TIA Peripheral arterial disease, history of peripheral arterial revascularization

3. Patients who have been taking lipid-lowering agents (statin or ezetimibe) for ≥4 weeks at the time of randomization

4. Patients who gave informed consent

Exclusion Criteria

1. Patients who have used lipid-lowering agents other than statin or ezetimibe within the last 3 months
2. A serum triglyceride on fasting >400 mg/dL
3. A history of muscular symptoms or rhabdomyolysis due to the use of statin
4. Hypersensitivity to rosuvastatin or ezetimibe
5. Labeled contraindications to rosuvastatin or rosuvastatin Severe renal impairment (CrCl <30 mL/min by Cockcroft-Gault formula or estimated GFR <30 mL/min / 1.73 m2 by MDRD equation) ALT, AST ≥3 × ULN or active liver disease CPK ≥3 × ULN
6. Enrollment of other clinical trials within 30 days
7. Any other issues that the treating physician assumes ineligible for participation in the trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
combination therapy group	Efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin	The combination therapy group will receive a single-pill combination of rosuvastatin 10 mg and ezetimibe 10 mg once daily.
intensive statin group	Efficacy and safety of combination therapy of moderate-intensity statin and ezetimibe compared to high-intensity statin	The subjects in the intensive statin group will receive rosuvastatin 20 mg once daily.

Primary Outcome Measures

Name	Time	Method
% change of low-density lipoprotein cholesterol	at 12 weeks	%change of LDL-C = (LDL-C at 12 weeks) - (LDL-C at baseline)/LDL-C at baseline \* 100

Secondary Outcome Measures

Name	Time	Method
% change of fasting glucose	at 12 and 24 weeks	fasting plasma glucose(mg/dL)
% change of serum cholesterol level	at 12 and 24 weeks	total cholesterol, LDL, HDL cholesterol, triglyceride (mg/dL)
proportion of participant with major adverse cardiovascular and cerebrovascular events(MACCE)	at 12 and 24 weeks	MACCE defined as a composite of the followings : cardiovascular death, acute myocardial infarction, unstable angina, stroke
% change of high-sensitivity C-reactive protein	at 12 and 24 weeks	hs-CRP(mg/dL)
% change of homeostatic model assessment for insulin resistance(HOMA-IR)	at 12 and 24 weeks	HOMA-IR = glucose \* insulin / 405(glucose mg/dL , insulin uIU/mL)
proportion of participant with statin-associated muscle symptoms	at 12 and 24 weeks	occurrence of statin-associated muscle symptoms
proportion of participant with creatinine phosphokinase elevation	at 12 and 24 weeks	proportion of CPK elevation ≥4 or ≥10 upper normal of limit
proportion of participant with liver function test abnormality	at 12 and 24 weeks	proportion of AST/ALT elevation ≥4 or ≥10 upper normal of limit

Trial Locations

Locations (1)

Seoul National University Bundang Hospital; 🇰🇷 Seongnam, Gyeonggi-do, Korea, Republic of