Clinical trial NCT03403556: High-intensity Rosuvastatin vs. Moderate-intensity Rosuvastatin/Ezetimibe in High Atherosclerotic Cardiovascular Disease Risk Patients With Type 2 Diabetes
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Atherosclerotic Cardiovascular Disease
Type 2 Diabetes
Keywords: High ASCVD risk patients with type 2 diabetes
Lead sponsor: Yuhan Corporation
Sponsor class: INDUSTRY
First posted: 2018-01-18
Enrollment: 140
Sex: ALL
Minimum age (years): 40
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

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

Eligibility criteria: * ≥ 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

Primary outcomes:
measure: Mean percent change from baseline to week 24 in low-density lipoprotein cholesterol (LDL-C)
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Proportion of subjects achieving < 7.5% 10-year ASCVD risk without withdrawn due to adverse events
timeFrame: Up to 24 weeks
measure: Mean change from baseline to week 12 and to week 24 in 10-year ASCVD risk
timeFrame: Up to 12 weeks, Up to 24 weeks
measure: 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
timeFrame: Up to 24 weeks
measure: 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)
timeFrame: Up to 24 weeks
measure: Mean change from baseline to week 24 in Hepatic Steatosis Index (HSI)
timeFrame: Up to 24 weeks
measure: Mean change from baseline to week 24 in Fatty Liver Index (FLI)
timeFrame: Up to 24 weeks
measure: Mean change from baseline to week 24 in non-alcoholic fatty liver disease liver fat score (NAFLD-LFS)
timeFrame: Up to 24 weeks
measure: Mean change from baseline to week 24 in HbA1c
timeFrame: Up to 24 weeks
measure: Mean change from baseline to week 24 in fasting plasma glucose (FPG)
timeFrame: Up to 24 weeks
measure: Mean change from baseline to week 24 in sCD36
timeFrame: Up to 24 weeks
measure: Mean change from baseline to week 24 in HOMA-IR
timeFrame: Up to 24 weeks
measure: Mean change from baseline to week 24 in HOMA-B
timeFrame: Up to 24 weeks
Other outcomes:
Locations:
city: Daegu
country: Korea, Republic of
facility: Daegu Catholic University Medical Center
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
Study officials:
References: