Comparison of Low-Intensity Statin Plus Ezetimibe Versus High-Intensity Statin Therapy on Risk of New-Onset Diabetes Mellitus (PROVE-DM)

  • End date
    Dec 30, 2027
  • participants needed
  • sponsor
    Seung-Whan Lee, M.D., Ph.D.
Updated on 9 April 2023


This study is to evaluating the impact of low-intensity statin plus ezetimibe versus high-intensity statin therapy on risk of new-onset diabetes mellitus in patients with atherosclerotic cardiovascular disease who have prediabetes.


The PROVE-DM trial is a multi-center, open-labeled, randomized controlled trial comparing two different lipid lowering strategies in patients with prediabetes and established atherosclerosis. Patients with prediabetes and documented atherosclerosis, either clinical or unequivocal on imaging are eligible for enrollment. The detailed information for inclusion and exclusion criteria is described below in the session 4. Patients meeting inclusion criteria without any exclusion criteria are assessed to be able to tolerate high-intensity statin therapy while achieving the target LDL level (LDL cholesterol < 70 mg/dL for established atherosclerotic cardiovascular disease or LDL cholesterol < 100 mg/dL for mild to moderate coronary artery disease) through a run-in period of 2 to 6 months. (Run in period was set as a screening process to reduce drop-out cases that cannot withstand high-intensity statins or cannot accomplished target LDL levels) Eligible patients will be randomized to high-intensity statin (rosuvastatin 20 mg qd) or low-intensity statin plus ezetimibe (rosuvastatin 5/10mg/ ezetimibe 10 mg qd). Patients will be followed-up clinically at 6, 12 months and then annually up to 3 years after randomization. Follow-up measurement of DM diagnostic criteria (fasting plasma glucose, plasma Hb A1c, oral glucose tolerance test) and lipid profile is intended to 1) provide evidence of new onset DM, 2) evaluate effectiveness of lowering LDL cholesterol. To ensure the accurate assessment of the clinical outcomes, cardiovascular safety end point (death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke), any arterial revascularization, any potential side effects of statin and all-cause mortality were also investigated.

Condition Pre Diabetes, ASCVD
Treatment high-intensity statin arm, low-intensity statin plus ezetimibe
Clinical Study IdentifierNCT05579626
SponsorSeung-Whan Lee, M.D., Ph.D.
Last Modified on9 April 2023


Yes No Not Sure

Inclusion Criteria

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

Exclusion Criteria

Patient's pregnant or breast-feeding or child-bearing potential
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
Hypersensitivity to any of statin and ezetimibe
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