AzTrials
AzTrials

Pre DiabetesPhase 4NCT05579626

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

A Phase 4 study testing high-intensity statin arm and low-intensity statin plus ezetimibe in people with Pre Diabetes and ASCVD, run by Seung-Whan Lee, M.D., Ph.D. at 31 sites in South Korea.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Pre Diabetes, ASCVD
What is being tested?
high-intensity statin arm and low-intensity statin plus ezetimibe
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4,000 participants
Where
31 sitesSouth Korea
Study dates
14 Mar 2023to 31 Dec 2030
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 18Show fewer
  • 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)
  • Patients who have never taken a statin or who do not have problems adhering to statin therapy
  • 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.
  • 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.

Who cannot join

  • 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
Show all 17Show fewer
  • Alcoholism.
  • Hypersensitivity to any of statin and ezetimibe.
  • 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).
  • 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.
  • 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)

Trial locations and contacts

31 sites in 1 country. Contact the study team or a site near you to ask about taking part.

31 sites in 1 country

South Korea31 sites

  • Bycheon Sejong Hospital

    Bucheon-si

  • Gyeongsang National University Changwon Hospital

    Changwon

  • Chungbuk National University Hospital

    Cheonju

  • Gangwon National University Hospital

    Chuncheon

  • Daegu Catholic University Medical Center

    Daegu

  • Keimyung University Dongsan Medical Center

    Daegu

  • Yungnam universury Hospital

    Daegu

  • Chungnam National University Sejong Hospital

    Daejeon

  • Konyang University Hospital

    Daejeon

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

    Daejeon

  • Gangneung Asan Hospital

    Gangneung

  • Chonnam National University Hospital

    Gwangju

  • Inje University Haeundae Paik Hospital

    Haeundae

  • Hallym University Dongtan Sacred Heart Hospital

    Hwaseong-si

  • Gachon University Gil Medical Center

    Incheon

  • Jeju National University Hospital

    Jeju City

  • Gyeongsang National University Hospital

    Jinju

  • Chungnam National University Hospital

    Jungnam

  • Dong-A Medical Center

    Pusan

  • Inje University Busan Paik Hospital

    Pusan

  • Kosin University Gospel Hospital

    Pusan

  • Pusan National University Yangsan Hospital

    Pusan

  • Asan Medical Center

    Seoul

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

    Seoul

  • Ewha womans university seoul hospital

    Seoul

  • Kangdong Sacred Heart Hospital

    Seoul

  • Korea University Anam Hospital

    Seoul

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

    Seoul

  • VHS Medical Center

    Seoul

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

    Suwon

  • Ulsan university hospital

    Ulsan

Other trials in South Korea

About this study

Official title: 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 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.

Read the detailed description

Statins [3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA) inhibitors] decreases the risk of death and cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). The cardiovascular benefits of high-intensity compared to low-intensity statin therapy are well demonstrated, and current guidelines recommend high-intensity statin therapy for high-risk patients with ASCVD . However, statin-related side effects are usually dose-dependent, and more frequent in patients receiving high-intensity statin therapy. A meta-analysis of 13 statin trials with 91,140 individuals reported that statin therapy is associated with an increased risk of developing diabetes mellitus (DM) over a 4-year period compared to patients randomized to placebo (odds ratio [OR] 1.09; 95% confidence interval [CI] 1.02-1.17). The high-intensity statin was associated with an increased risk of new onset DM compared with low doses of statins (HR 1.22, 95% CI 1.15 to 1.29). In addition, meta-analysis of five intensive-dose statin trials suggested the likelihood of developing DM is also higher with high-intensity statins compared to moderate-intensity statins in 32,752 subjects over a mean follow-up of 4.9 years (OR 1.12; 95% CI 1.04-1.22).

Prediabetes is a risk factor for ASCVD with a rapidly increasing prevalence worldwide (7.5% in 2019 and projected to reach 8.0% by 2030). Every year about 6.4-12.1% of these people develop diabetes and the risk increase further in the elderly, obese patients, and patients with metabolic syndrome. Considering that the risk of ASCVD increases even before the onset of DM, prediabetes patients need aggressive statin therapy for primary and secondary prevention. However, high-intensity therapy may increase the risk of new-onset DM, especially in patients with pre-diabetes. For this reason, caution is required in determining statin treatment strategies. An effectiveness of statins in reducing cardiovascular events depends on an absolute reduction in low-density lipoprotein (LDL) cholesterol levels and the duration of statin administration A combination therapy of low-dose statin and ezetimibe is an equivalent approach to high-dose statin therapy for decreasing LDL cholesterol level by 50% and achieving LDL cholesterol target level. This strategy is therefore considered attractive to reduce the risk of new-onset DM, and often used because of concerns regarding statin-induced diabetes in pre-diabetic patients. However, there are no data to compare the incidence of new onset DM as a pre-specified primary outcome between two lipid lowering strategies among prediabetic patients with ASCVD. Herein, we designed the study of comparison of low-intensity statin plus ezetimibe versus high-intensity statin therapy on risk of new-onset DM (PROVE-DM), a phase 4 trial involving patients with established atherosclerosis requiring lipid lowering (statin or ezetimibe) agents, comparing a regimen of high-intensity statin (rosuvastatin 20 mg) with the low intensity statin and ezetimibe (rosuvastatin 5 mg plus ezetimibe 10 mg)

Conditions
Pre Diabetes, ASCVD
Being tested
high-intensity statin arm, low-intensity statin plus ezetimibe
Medical subject headings
Glucose Intolerance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • high-intensity statin armDrug

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

  • low-intensity statin plus ezetimibeDrug

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

Study groups in NCT05579626
Study groupRoleWhat they receive
high-intensity statin armActive comparator(high-intensity statin arm): rosuvastatin 20 mg PO qd, once daily
Receives: Drug: high-intensity statin arm
low-intensity statin plus ezetimibe armActive comparator(low-intensity statin plus ezetimibe arm ): rosuvastatin 5mg /ezetimibe 10mg PO qd), once daily
Receives: Drug: low-intensity statin plus ezetimibe

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 36months after randomization

  2. Number of Participants with death

    Major adverse cardiac events are defined as all-cause death

    Measured: 36months after randomization

Secondary outcomes (5)

  1. Composite cardiovascular safety

    death from cardiovascular cause, non fatal myocardial infarction of nom fatal stroke

    Measured: 36months after randomization

  2. Any arterial revascularization

    Any arterial revascularization (carotid, coronary aorta or peripheral artery) Any arterial revascularization (carotid, coronary aorta or peripheral artery)

    Measured: 36months after randomization

  3. Any potential side effect

    Any potential side effect

    Measured: 36months after randomization

  4. Each component of the diabetes-mellitus diagnosis criteria

    Each component of the diabetes-mellitus diagnosis criteria

    Measured: 36months after randomization

  5. All cause mortality

    All cause mortality

    Measured: 36months after randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Oct 2022
  2. Study start14 Mar 2023
  3. Primary completion31 Dec 2030 (estimated)
  4. Study completion31 Dec 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
4,000 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05579626
Sponsor's protocol ID
2022-1275
Status last verified
Jan 2026
First submitted
11 Oct 2022
Last updated
7 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing high-intensity statin arm and low-intensity statin plus ezetimibe in people with Pre Diabetes and ASCVD, run by Seung-Whan Lee, M.D., Ph.D. at 31 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants with New-onset-DM (time frame: 36months after randomization). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05579626.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in