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

Launched by SEUNG-WHAN LEE, M.D., PH.D. · Oct 12, 2022

Keywords

ClinConnect Summary

The PROVE-DM clinical trial is studying how different types of cholesterol-lowering medications affect the risk of developing diabetes in patients who have prediabetes and a history of heart disease. Specifically, it compares a low-intensity statin combined with ezetimibe (another cholesterol-lowering medication) to a high-intensity statin alone. This research aims to find out which treatment is better at preventing new-onset diabetes in these patients.

To participate in the trial, you need to be between 18 and 75 years old and diagnosed with prediabetes, which means your blood sugar levels are higher than normal but not high enough to be diabetes. You should also have a history of heart disease, such as a heart attack or stroke. Participants will follow a healthy diet throughout the study and have regular check-ups to monitor their health. It’s important to know that individuals with certain medical conditions, like severe kidney disease or those who are pregnant, will not be eligible for this trial. If you qualify and decide to participate, you’ll be helping researchers understand how to better manage heart health and diabetes risk.

Gender

ALL

Eligibility 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%)
• • ThoracoAbdominal Aortic Aneurysm
• • 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 have never taken a statin or who do not have problems adhering to statin therapy
• • 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. 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).
• • 3. Chronic kidney disease (eGFR\<30 ml/min/1.73m2) or dialysis-dependent renal failure
• • 4. Uncontrolled hypothyroidism.
• • 5. Personal or family history of hereditary muscular disorders.
• • 6. History of muscular toxicity with a statin
• • 7. Alcoholism.
• • 8. Hypersensitivity to any of statin and ezetimibe.
• • 9. 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).
• • 10. Any history of hemorrhagic stroke or intracranial hemorrhage within the past 6 months
• • 11. Any surgery requiring discontinuation of statin and/or ezetimibe is planned within 6 months after randomization
• • 12. 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.
• • 13. 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.
• • 14. Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST \> 3 times upper limit of normal) or (Total bilirubin\> 2 times upper limit of normal).
• • 15. Life expectancy \< 1 years for any non-cardiac or cardiac causes
• • 16. Unwillingness or inability to comply with the procedures described in this protocol.
• • 17. People who have previously been diagnosed with diabetes and are taking lifestyle modification and oral hypoglycemic agent (OHA) or insulin (In woman, gestational diabetes is included)