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

Type 2 Diabetes Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03403556
• Other study ID #: CREATE
• Status: Recruiting
• Phase: Phase 4
• Start date: March 27, 2018
• Est. completion date: December 2021

Study information

• Verified date: December 2020
• Source: Yuhan Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: December 2021
• Est. primary completion date: October 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 74 Years

Eligibility

• = 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

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Rosuvamibe
Rosuvastatin 10mg/Ezetimibe10mg qd for 24 weeks
• Monorova
Rosuvastatin 20mg qd for 24 weeks

Locations

Country	Name	City	State
Korea, Republic of	Daegu Catholic University Medical Center	Daegu
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Yeungnam University Medical Center	Daegu
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Gyeonggi-do
Korea, Republic of	Korea University Anam Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yuhan Corporation

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean percent change from baseline to week 24 in low-density lipoprotein cholesterol (LDL-C)		Up to 24 weeks
Secondary	Proportion of subjects achieving < 7.5% 10-year ASCVD risk without withdrawn due to adverse events		Up to 24 weeks
Secondary	Mean change from baseline to week 12 and to week 24 in 10-year ASCVD risk		Up to 12 weeks, Up to 24 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mean change from baseline to week 24 in non-alcoholic fatty liver disease liver fat score (NAFLD-LFS)		Up to 24 weeks
Secondary	Mean change from baseline to week 24 in HbA1c		Up to 24 weeks
Secondary	Mean change from baseline to week 24 in fasting plasma glucose (FPG)		Up to 24 weeks
Secondary	Mean change from baseline to week 24 in sCD36		Up to 24 weeks
Secondary	Mean change from baseline to week 24 in HOMA-IR		Up to 24 weeks
Secondary	Mean change from baseline to week 24 in HOMA-B		Up to 24 weeks