Comparing low-intensity statin plus ezetimibe to high-intensity statin therapy for diabetes risk in prediabetic patients with heart disease

Comparison of Low-Intensity Statin Plus Ezetimibe Versus High-Intensity Statin Therapy on Risk of New-Onset Diabetes Mellitus in Prediabetic Patients With Atherosclerotic Cardiovascular Disease

This study is testing if a lower dose of a cholesterol-lowering medication combined with another drug can help people with prediabetes and heart disease avoid developing diabetes compared to a higher dose of the cholesterol medication.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 4000 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Asan Medical Center (Academic / other)
• Locations: 23 sites (Bucheon and 22 other locations)
• Trial ID: NCT05579626 on ClinicalTrials.gov

What this trial studies

This study evaluates the effects of low-intensity statin therapy combined with ezetimibe versus high-intensity statin therapy on the risk of developing new-onset diabetes mellitus in patients with prediabetes and atherosclerotic cardiovascular disease (ASCVD). It aims to determine whether a lower intensity of statin therapy can mitigate the risk of diabetes, which has been associated with higher doses of statins. Participants will be men and women aged 18 to 75 who meet specific criteria for prediabetes and ASCVD. The study will involve monitoring the incidence of diabetes over a defined period.

Who should consider this trial

Good fit: Ideal candidates are men and women aged 18 to 75 with prediabetes and a history of atherosclerotic cardiovascular disease.

Not a fit: Patients who do not have prediabetes or those who do not require statin therapy for cardiovascular risk may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could help identify safer treatment options for patients at risk of diabetes while managing cardiovascular disease.

How similar studies have performed: Previous studies have indicated that high-intensity statin therapy is associated with an increased risk of diabetes, suggesting that this approach to comparing therapies is both relevant and necessary.

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)

Where this trial is running

Bucheon and 22 other locations

• Bycheon Sejong Hospital — Bucheon, Korea, Republic of (Recruiting)
• Gyeongsang National University Changwon Hospital — Changwon, Korea, Republic of (Recruiting)
• Chungbuk National University Hospital — Cheonju, Korea, Republic of (Recruiting)
• Gangwon National University Hospital — Chuncheon, Korea, Republic of (Recruiting)
• Daegu Catholic University Medical Center — Daegu, Korea, Republic of (Recruiting)
• Keimyung University Dongsan Medical Center — Daegu, Korea, Republic of (Recruiting)
• Yungnam universury Hospital — Daegu, Korea, Republic of (Not_yet_recruiting)
• Chungnam National University Sejong Hospital — Daejeon, Korea, Republic of (Recruiting)
• Konyang University Hospital — Daejeon, Korea, Republic of (Recruiting)
• Gangneung Asan Hospital — Gangneung, Korea, Republic of (Recruiting)
• Gachon University Gil Medical Center — Incheon, Korea, Republic of (Not_yet_recruiting)
• Jeju National University Hospital — Jeju, Korea, Republic of (Not_yet_recruiting)
• Gyeongsang National University Hospital — Jinju, Korea, Republic of (Recruiting)
• Dong-A Medical Center — Pusan, Korea, Republic of (Recruiting)
• Inje University Busan Paik Hospital — Pusan, Korea, Republic of (Recruiting)
• Kosin University Gospel Hospital — Pusan, Korea, Republic of (Enrolling_by_invitation)
• Pusan National University Yangsan Hospital — Pusan, Korea, Republic of (Not_yet_recruiting)
• Asan Medical Center — Seoul, Korea, Republic of (Recruiting)
• Ewha womans university seoul hospital — Seoul, Korea, Republic of (Not_yet_recruiting)
• Kangdong Sacred Heart Hospital — Seoul, Korea, Republic of (Not_yet_recruiting)
• Korea University Anam Hospital — Seoul, Korea, Republic of (Recruiting)
• The Catholic Univ. of Korea Eunpyeong St. Mary's hospital — Seoul, Korea, Republic of (Recruiting)
• The Catholic University of Korea, St. Vincent's Hospital — Suwon, Korea, Republic of (Not_yet_recruiting)

Study contacts

• Principal investigator: Seung-Whan Lee, MD — Asan Medical Center
• Study coordinator: Su-Bin Shin, RN

Conditions Pre Diabetes; ASCVD