Comparison of Pitavastatin Plus Ezetimibe Versus High-Intensity Statin Therapy on Risk of New-Onset Diabetes Mellitus

April 24, 2025 updated by: Dr. Cheol Woong Yu, Korea University Anam Hospital

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

The AVOID-DM trial is a multicenter, prospective, randomized study comparing the risk of new-onset diabetes mellitus (DM) between two cholesterol-lowering strategies in patients with prediabetes and established atherosclerotic cardiovascular disease (ASCVD). The study evaluates pitavastatin plus ezetimibe combination therapy versus high-intensity statin monotherapy (rosuvastatin 20 mg). Enrolling 2,000 non-diabetic participants with ASCVD, subjects are randomized 1:1 into the two treatment arms. The primary outcome is the incidence of new-onset DM over a follow-up period of up to 36 months. Secondary outcomes include cardiovascular events, changes in LDL cholesterol, fasting glucose, HbA1c, and insulin resistance. This trial hypothesizes that the combination therapy will achieve LDL targets with a lower risk of new-onset DM compared to high-intensity statin monotherapy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

2000

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of, 02841
        • Recruiting
        • Korea University Anam Hospital
        • Contact:
          • Korea Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age Requirement:

    • Patients aged 18 years or older.

Glycemic Status:

  • Patients who are not taking oral hypoglycemic agents (OHAs) and meet all of the following criteria:

    • Fasting glucose less than 126 mg/dL.*
    • HbA1c less than 6.5%.
    • Plasma glucose less than 200 mg/dL after 2 hours during a 75 g oral glucose tolerance test (OGTT).*Note: For fasting glucose, two measurements of 126 mg/dL or greater within 3 months are required for a diagnosis of diabetes.

Cardiovascular Disease:

  • Patients with established atherosclerotic cardiovascular disease, defined as having at least one of the following:

    • Coronary Heart Disease (CHD):

      • Documented history of myocardial infarction (MI).

      • History of coronary revascularization.

        • 50% stenosis of a major epicardial coronary artery confirmed by cardiac catheterization, computed tomography (CT), or coronary angiography.

    • Cerebrovascular Disease:

      >History of stroke of atherosclerotic origin.

      • History of carotid revascularization.

        >≥50% stenosis of the carotid artery confirmed by X-ray angiography, magnetic resonance (MR) angiography, CT angiography, or Doppler ultrasound.

    • Symptomatic Peripheral Arterial Disease (PAD):

      >Intermittent claudication with an ankle-brachial index (ABI) of 0.90 at rest.

      • Intermittent claudication with ≥50% stenosis of a peripheral artery (excluding the carotid artery) confirmed by X-ray angiography, MR angiography, CT angiography, or Doppler ultrasound.
      • History of revascularization of peripheral arteries (excluding carotid arteries).
      • Lower extremity amputation at or above the ankle due to atherosclerotic disease (excluding trauma or osteomyelitis).

Dietary Requirements:

  • Patients must be on a stable diet prior to randomization and able to adhere to the National Cholesterol Education Program (NCEP) Therapeutic Lifestyle Change (TLC) diet or an equivalent throughout the study.

Informed Consent:

  • Subjects or their legal representatives must provide written informed consent to the study protocol and clinical follow-up schedule.
  • An informed consent form approved by the institutional review board (IRB)/ethics committee of the study site must be signed.

Exclusion Criteria:

  • Patient is pregnant or breastfeeding or of childbearing potential.
  • Requires concomitant administration of strong 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 an inherited muscle disorder.
  • History of statin-induced muscle toxicity.
  • Alcohol-dependent person.
  • Hypersensitivity to statins and ezetimibe.
  • Hemodynamic instability at the time of enrollment: cardiogenic shock, refractory ventricular arrhythmia, or congestive heart failure (New York Heart Association class IV) at randomization.
  • History of hemorrhagic stroke or intracranial hemorrhage, TIA, or ischemic stroke within the past 6 months.
  • Planned surgery requiring discontinuation of statins or ezetimibe within 6 months of randomization.
  • Current treatment for active cancer.
  • Clinically significant abnormal findings identified at the screening visit, physical examination, laboratory tests, or electrocardiogram that, in the investigator's judgment, may interfere with safe completion of the study.
  • Liver disease or biliary obstruction, elevated liver enzymes (ALT or AST > the upper limit of normal) or elevated total bilirubin (total bilirubin > 2 times the upper limit of normal) at screening.
  • Life expectancy for noncardiac or cardiac causes < 1 year.
  • Unwillingness or inability to comply with the procedures described in this protocol.
  • Previously diagnosed with diabetes mellitus and compliant with lifestyle modification and taking oral hypoglycemic agents (OHAs) or insulin.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combination therapy
fixed dose single-pill combination of pitavastatin 4mg plus ezetimibe 10mg
Drug: Combination therapy
  • pitavastatin 4mg
  • ezetimibe 10mg
Active Comparator: High intensity statin monotherapy
Rosuvastatin 20mg
Drug: High intensity statin monotherapy
rosuvastatin 20mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
new-onset diabetes mellitus meeting diagnostic criteria for conventional diabetes during the treatment period
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
1. Composite of major clinical events of cardiovascular disease (death from cardiovascular disease, nonfatal myocardial infarction or nonfatal stroke)
Time Frame: 3 years
3 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Death from any cause
Time Frame: 3 years
3 years
Reperfusion procedure for any type of artery
Time Frame: 3 years
3 years
3. Individual components of the composite of major clinical events of cardiovascular disease
Time Frame: 3 years
3 years
An element of the criteria met at diagnosis of diabetes mellitus
Time Frame: 3 years
3 years
HOMA-IR
Time Frame: 3 years
3 years
Incidence of statin side effect
Time Frame: 3 years
3 years
Drug Adherence
Time Frame: 3 years
Proportion of patients achieving ≥80% adherence to prescribed medication from baseline to 3 years
3 years
Change in LDL cholesterol during follow-up
Time Frame: 3 years
3 years
Change in HbA1c during follow-up
Time Frame: 3 years
3 years
Change in Fasting glucose during follow-up
Time Frame: 3 years
3 years
Change in Insulin during follow-up
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Korea University Anam Hospital

Collaborators

Daewon Pharmaceutical Co., Ltd.
Samjin Pharmaceutical Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 25, 2025

Primary Completion (Estimated)

August 31, 2029

Study Completion (Estimated)

January 31, 2030

Study Registration Dates

First Submitted

January 5, 2025

First Submitted That Met QC Criteria

January 5, 2025

First Posted (Actual)

January 10, 2025

Study Record Updates

Last Update Posted (Actual)

April 27, 2025

Last Update Submitted That Met QC Criteria

April 24, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AVOIDM

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

The corresponding author had full access to all the data in the study and takes responsibility for its integrity and the data analysis. The data are available upon reasonable request.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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