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

NCT05579626 | Enrolling By Invitation Phase 4 DMC

• 1 other identifier: 2022-1275
• Study Type: interventional
• Target: 4,000
• Locations: 1 country
• Sites: 31

Brief Summary

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.

Conditions

Pre Diabetes; ASCVD

Outcome Measures

Primary Outcomes (2)

• Number of Participants with New-onset-DM

  New onset DM was defined on the the basis of the American Diabetes association guideline if two abnormal test results of following criteria are existed from the same sample or in two separate test samples. 1. fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours OR 2. 2 hour plasma glucose during a 75 g oral glucose tolerance test (OGTT) ≥200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water OR 3. HbA1C ≥6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP (National Glycohemoglobin Standardization Program) certified and standardized to the DCCT (Diabetes Control and Complication Trial) assay.

  36months after randomization

• Number of Participants with death

  Major adverse cardiac events are defined as all-cause death

  36months after randomization

Secondary Outcomes (5)

• Composite cardiovascular safety

  36months after randomization

• Any arterial revascularization

  36months after randomization

• Any potential side effect

  36months after randomization

• Each component of the diabetes-mellitus diagnosis criteria

  36months after randomization

• All cause mortality

  36months after randomization

Study Arms (2)

high-intensity statin arm

ACTIVE COMPARATOR

(high-intensity statin arm): rosuvastatin 20 mg PO qd, once daily

Drug: high-intensity statin arm

low-intensity statin plus ezetimibe arm

ACTIVE COMPARATOR

(low-intensity statin plus ezetimibe arm ): rosuvastatin 5mg /ezetimibe 10mg PO qd), once daily

Drug: low-intensity statin plus ezetimibe

Interventions

high-intensity statin arm DRUG

•high-intensity statin strategy (standard arm): rosuvastatin 20 mg PO qd, once daily

high-intensity statin arm

low-intensity statin plus ezetimibe DRUG

•low-intensity statin plus ezetimibe strategy (experimental arm): rosuvastatin 5mg /ezetimibe 10mg PO qd), once daily

low-intensity statin plus ezetimibe arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%)
• 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)

You may not qualify if:

• 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
• Alcoholism.
• Hypersensitivity to any of statin and ezetimibe.
• 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) or (Total bilirubin\> 2 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.

Sponsors & Collaborators

• Seung-Whan Lee, M.D., Ph.D.: lead
• Yuhan Corporation: collaborator

Study Sites (31)

Bycheon Sejong Hospital

Bucheon-si, South Korea

Location

Gyeongsang National University Changwon Hospital

Changwon, South Korea

Location

Chungbuk National University Hospital

Cheonju, South Korea

Location

Gangwon National University Hospital

Chuncheon, South Korea

Location

Daegu Catholic University Medical Center

Daegu, South Korea

Location

Keimyung University Dongsan Medical Center

Daegu, South Korea

Location

Yungnam universury Hospital

Daegu, South Korea

Location

Chungnam National University Sejong Hospital

Daejeon, South Korea

Location

Konyang University Hospital

Daejeon, South Korea

Location

the Catholic University of Korea, Daejeon St. Mary'S Hospital

Daejeon, South Korea

Location

Gangneung Asan Hospital

Gangneung, South Korea

Location

Chonnam National University Hospital

Gwangju, South Korea

Location

Inje University Haeundae Paik Hospital

Haeundae, South Korea

Location

Hallym University Dongtan Sacred Heart Hospital

Hwaseong-si, South Korea

Location

Gachon University Gil Medical Center

Incheon, South Korea

Location

Jeju National University Hospital

Jeju City, South Korea

Location

Gyeongsang National University Hospital

Jinju, South Korea

Location

Chungnam National University Hospital

Jungnam, South Korea

Location

Dong-A Medical Center

Pusan, South Korea

Location

Inje University Busan Paik Hospital

Pusan, South Korea

Location

Kosin University Gospel Hospital

Pusan, South Korea

Location

Pusan National University Yangsan Hospital

Pusan, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Catholic University of Korea, Seoul ST. Mary's Hospital.

Seoul, South Korea

Location

Ewha womans university seoul hospital

Seoul, South Korea

Location

Kangdong Sacred Heart Hospital

Seoul, South Korea

Location

Korea University Anam Hospital

Seoul, South Korea

Location

The Catholic Univ. of Korea Eunpyeong St. Mary's hospital

Seoul, South Korea

Location

VHS Medical Center

Seoul, South Korea

Location

The Catholic University of Korea, St. Vincent's Hospital

Suwon, South Korea

Location

Ulsan university hospital

Ulsan, South Korea

Location

MeSH Terms

Conditions

Glucose Intolerance

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Seung-Whan Lee, MD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 11, 2022
• First Posted: October 14, 2022
• Study Start: March 14, 2023
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (31)