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

• Status: Not yet recruiting
• Trial end date: 2027-12-30
• Target enrollment: 0
• Participant gender: All

Summary

A multicenter, prospective randomized study 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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: CardioVascular Research Foundation, Korea
• Collaborator: Yuhan Corporation
• Treatments: Ezetimibe; Hydroxymethylglutaryl-CoA Reductase Inhibitors

Criteria

Inclusion Criteria:

1. 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

1. IFG: fasting plasma glucose (FPG) 100 to 125 mg/dL

2. IGT: 2 hours post-load glucose on the 75g OGTT (oral glucose tolerance test) 140 to 199 mg/dL

3. HbA1c: 5.7 to 6.4%

2. 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)

3. Patients who were not given statins (statin naive) or who were taking statins below the moderate -intensity.

4. 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.

5. 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:

1. Patient's pregnant or breast-feeding or child-bearing potential.

2. The one who used to take high intensity statins. (40mg or more of atorvastatin, 20mg or more of rosuvastatin)

3. 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).

4. Chronic kidney disease (eGFR<30 ml/min/1.73m2) or dialysis-dependent renal failure

5. Uncontrolled hypothyroidism.

6. Personal or family history of hereditary muscular disorders.

7. History of muscular toxicity with a statin

8. Alcoholism.

9. Hypersensitivity to any of statin and ezetimibe.

10. 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).

11. Any history of hemorrhagic stroke or intracranial hemorrhage within the past 6 months

12. Any surgery requiring discontinuation of statin and/or ezetimibe is planned within 6 months after randomization

13. 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.

14. 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.

15. Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 3 times upper limit of normal).

16. Life expectancy < 1 years for any non-cardiac or cardiac causes

17. Unwillingness or inability to comply with the procedures described in this protocol.

18. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period.

19. People who have previously been diagnosed with diabetes and are taking lifestyle modification and oral hypoglycemic agent (OHA) or insulin