Comparison of Low-Intensity Statin Plus Ezetimibe Versus High-Intensity Statin Therapy on Risk of New-Onset Diabetes Mellitus (PROVE-DM)
Pre Diabetes, ASCVD
About this trial
This is an interventional prevention trial for Pre Diabetes
Eligibility Criteria
Inclusion Criteria:
Men or women between the ages of 18 and 75 years who have prediabetes
-Prediabetes consists of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or HbA1c
- IFG: fasting plasma glucose (FPG) 100 to 125 mg/dL
- IGT: 2 hours post-load glucose on the 75g OGTT (oral glucose tolerance test) 140 to 199 mg/dL
- HbA1c: 5.7 to 6.4%
Patient requiring high-intensity statin due to high risk of a future cardiovascular event if at least one of the following criteria is present via patient history, physical examination, or medical records at the time of screening (Clinically documented ASCVD)
- acute coronary syndrome (MI or unstable angina)
- stable angina
- coronary revascularization (PCI, CABG, and other arterial revascularization procedure)
- stroke or TIA
peripheral arterial disease (<0.9 performed by a vascular lab or angiogram (including CTA) showing ≥ 50%) Unequivocally documented ASCVD on imaging
- significant plaque on coronary angiography on CT (mild, moderate, severe coronary artery disease)
- significant plaque on carotid ultrasound (mild, moderate, severe carotid disease)
- Patients who were not given statins (statin naive) or who were taking statins below the moderate -intensity.
- Patient must have been on a stable diet prior to randomization and willing to follow the NCEP (national Cholesterol Education Program) TLC (therapeutic lifestyle changes) diet, or equivalent diet, throughout the study.
- The patient or guardian agrees to the study protocol and the schedule of clinical follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site.
Exclusion Criteria:
- Patient's pregnant or breast-feeding or child-bearing potential.
- The one who used to take high intensity statins. (40mg or more of atorvastatin, 20mg or more of rosuvastatin)
- Concomitant administration of potent inhibitors of CYP3A4 (itraconazole, ketoconazole, protease inhibitors, erythromycin, clarithromycin, telithromycin and nefazodone) or CYP2C9 (relative contraindication not dependent on CYP450 statins).
- Chronic kidney disease (eGFR<30 ml/min/1.73m2) or dialysis-dependent renal failure
- Uncontrolled hypothyroidism.
- Personal or family history of hereditary muscular disorders.
- History of muscular toxicity with a statin
- Alcoholism.
- Hypersensitivity to any of statin and ezetimibe.
- Hemodynamic unstable conditions at the time of inclusion: cardiogenic shock at the time of randomization, refractory ventricular arrhythmias, or congestive heart failure (New York Heart Association class IV).
- Any history of hemorrhagic stroke or intracranial hemorrhage within the past 6 months
- Any surgery requiring discontinuation of statin and/or ezetimibe is planned within 6 months after randomization
- A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer.
- Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study.
- Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 3 times upper limit of normal).
- Life expectancy < 1 years for any non-cardiac or cardiac causes
- Unwillingness or inability to comply with the procedures described in this protocol.
- Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.
- People who have previously been diagnosed with diabetes and are taking lifestyle modification and oral hypoglycemic agent (OHA) or insulin
Sites / Locations
- Bycheon Sejong Hospital
- Gyeongsang National University Changwon Hospital
- Chungbuk National University Hospital
- Gangwon National University Hospital
- Daegu Catholic University Medical Center
- Keimyung University Dongsan Medical Center
- Chungnam National University Sejong Hospital
- Gangneung Asan Hospital
- Gachon University Gil Medical Center
- Jeju National University Hospital
- Gyeongsang National University Hospital
- Dong-A Medical Center
- Inje University Busan Paik Hospital
- Kosin University Gospel Hospital
- Pusan National University Yangsan Hospital
- Asan Medical CenterRecruiting
- Hallym University Medical Center-Kangdong
- Korea University Anam Hospital
- The Catholic Univ. of Korea Eunpyeong St. Mary's hospital
- The Catholic University of Korea, St. Vincent's Hospital
- Ulsan University Hospital
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
high-intensity statin arm
low-intensity statin plus ezetimibe arm
(high-intensity statin arm): rosuvastatin 20 mg PO qd, once daily
(low-intensity statin plus ezetimibe arm ): rosuvastatin 5mg /ezetimibe 10mg PO qd), once daily