High-intensity Rosuvastatin vs. Moderate-intensity Rosuvastatin/Ezetimibe in High Atherosclerotic Cardiovascular Disease Risk Patients With Type 2 Diabetes

A Randomized, Multicenter, Open, Parallel, Phase 4 Study to Compare the Efficacy and Safety Between High-intensity Rosuvastatin and Moderate-intensity Rosuvastatin/Ezetimibe in High ASCVD Risk Patients With Type 2 diabEtes (CREATE Study)

To assess the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe compared to high-intensity rosuvastatin in high atherosclerotic cardiovascular disease risk patients with type 2 diabetes

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes; Atherosclerotic Cardiovascular Disease
• Intervention / Treatment: Drug: Rosuvamibe; Drug: Monorova

Detailed Description

This study is to assess the efficacy and safety of Rosuvamibe® (rosuvastatin 10mg/ezetimibe 10mg) vs. rosuvastatin 20mg treated for 24 weeks in atherosclerotic cardiovascular disease risk (≥ 7.5%) patients with type 2 diabetes

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daegu, Korea, Republic of
    • Not yet recruiting
    • Keimyung University Dongsan Medical Center
  • Daegu, Korea, Republic of
    • Recruiting
    • Yeungnam University Medical Center
    • Contact: Kyuchang Won; Phone Number: 82 53-620-3846; Email: kcwon@med.yu.ac.kr
  • Daegu, Korea, Republic of
    • Not yet recruiting
    • Daegu Catholic University Medical Center
  • Daegu, Korea, Republic of
    • Not yet recruiting
    • Kyungpook National University Hospital
  • Gyeonggi-do, Korea, Republic of
    • Not yet recruiting
    • The Catholic University of Korea, St. Vincent'S Hospital
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Korea University Anam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• ≥ 40 and < 75 years of age at the time of informed consent
• Estimated 10-year ASCVD (atherosclerotic cardiovascular disease) risk ≥ 7.5% with type 2 diabetes according to the American Diabetes Association criteria in screening
• HbA1c ≥ 6% and < 10% in screening
• Body mass index (BMI) ≤ 35kg/m2 in screening
• Female of childbearing with a negative pregnancy test who must agree to use contraception (including those not medically pregnant) during the study period
• Written consent after being informed of the purpose and contents of the clinical trial and the characteristics and risks of IPs

Exclusion Criteria:

• Type 1 diabetes
• Chronic hepatitis B or chronic hepatitis C, severe hepatic dysfunction (AST, ALT, ALP or CPK ≥ 3 x ULN) in screening
• Heavy drinking > 210g per week in screening
• Estimated GFR < 30mL/min/1.73m2 using the CKD-EPI formula in screening
• Undergoing renal replacement therapy (hemodialysis or peritoneal dialysis) in screening
• Having used other statin (HMG-CoA converting enzyme inhibitors) than Rosuvastatin or fibrate drugs in the last 3 months before screening

• Taking any medication (ex. Fenofibrate, Omega 3 fatty acid, etc.) that may affect LDL

  * Can be enrolled after 4 week-washout

• Having used thiazolidinedione drugs in the last 3 months before screening
• Taking cyclosporine concomitantly
• Positive HIV test in screening
• Pregnant, breastfeeding, or childbearing women who are not likely to use the appropriate contraceptive methods as judged by investigator
• Subjects with a medical history of myopathy and rhabdomyolysis due to use of statin
• Hypersensitive to statin and ezetimibe

• Having endocrine or metabolic disease known to affect serum lipids or lipoproteins

  • Uncontrolled diabetes (HbA1c ≥ 10%)
  • Uncontrolled thyroid dysfunction (TSH ≥ 3 x ULN)
• Subjects with a medical history of acute arterial diseases such as unstable angina, myocardial infarction, transient ischemic attack, cerebrovascular disease, coronary artery bypass graft or percutaneous coronary intervention in the last 6 months before screening
• Subjects with a surgical history of gastrointestine or drug absorption disorders due to gastrointestinal disorders
• Insulin-treated
• Taking other IPs in the last 30 days before screening
• Subjects who cannot discontinue contraindications that may affect the treatment of all types of diabetes and/or hypercholesterolemia during the study period
• Subjects with a significant or unstable medical or psychological condition that is judged by investigator to be detrimental to safety or to successful participation in the trial
• Other conditions than the above who is deemed to be ineligible to participate in the trial by investigator

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: Rosuvamibe ® Tab.; Rosuvastatin 10mg/Ezetimibe10mg	Drug: Rosuvamibe; Rosuvastatin 10mg/Ezetimibe10mg qd for 24 weeks
Active Comparator: Monorova ® Tab.; Rosuvastatin 20mg	Drug: Monorova; Rosuvastatin 20mg qd for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean percent change from baseline to week 24 in low-density lipoprotein cholesterol (LDL-C)	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving < 7.5% 10-year ASCVD risk without withdrawn due to adverse events		Up to 24 weeks
Mean change from baseline to week 12 and to week 24 in 10-year ASCVD risk		Up to 12 weeks, Up to 24 weeks
Proportion of subjects achieving the comprehensive lipid target (LDL-C < 70mg/dL, Non-HDL-C < 100mg/dL, and Apolipoprotein B < 80mg/dL) without withdrawn due to adverse events		Up to 24 weeks
Mean change from baseline to week 24 in calculated LDL cholesterol(mg/dL), HDL cholesterol(mg/dL), Triglyceride(mg/dL), non-HDL cholesterol(mg/dL), Apolipoprotein B(mg/dL), Apolipoprotein A1(mg/dL)		Up to 24 weeks
Mean change from baseline to week 24 in Hepatic Steatosis Index (HSI)	hepatic steatosis index (HSI)= 8x(ALT/AST ratio)+BMI (+2, if female; +2, if diabetes mellitus)	Up to 24 weeks
Mean change from baseline to week 24 in Fatty Liver Index (FLI)	FLI scores will be calculated based on triglycerides, BMI, r-GT and Waist circumference. BMI(kg/m^2) will be calculated based on height(m) and weight(kg).	Up to 24 weeks
Mean change from baseline to week 24 in non-alcoholic fatty liver disease liver fat score (NAFLD-LFS)		Up to 24 weeks
Mean change from baseline to week 24 in HbA1c		Up to 24 weeks
Mean change from baseline to week 24 in fasting plasma glucose (FPG)		Up to 24 weeks
Mean change from baseline to week 24 in sCD36		Up to 24 weeks
Mean change from baseline to week 24 in HOMA-IR		Up to 24 weeks
Mean change from baseline to week 24 in HOMA-B		Up to 24 weeks

Collaborators and Investigators

• Sponsor: Yuhan Corporation

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2018
• Primary Completion (Anticipated): October 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: December 11, 2017
• First Submitted That Met QC Criteria: January 10, 2018
• First Posted (Actual): January 18, 2018

Study Record Updates

• Last Update Posted (Actual): December 14, 2020
• Last Update Submitted That Met QC Criteria: December 11, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: High ASCVD risk patients with type 2 diabetes
• Additional Relevant MeSH Terms: Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Endocrine System Diseases; Cardiovascular Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Atherosclerosis
• Other Study ID Numbers: CREATE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No