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NCT Number: NCT07524101

Moderate-Intensity Statin Plus Ezetimibe in CKD and ASCVD

The ULTRA-CKD trial is a prospective, randomized, open-label, multicenter trial designed to compare the efficacy and safety of moderate-intensity statin plus ezetimibe combination therapy versus high-intensity statin monotherapy in patients with chronic kidney disease (CKD) and concomitant atherosclerotic cardiovascular disease (ASCVD).

Patients with CKD are at very high risk for ASCVD. In this population, it is important to establish a lipid-lowering strategy that optimizes cardiovascular outcomes while ensuring long-term safety. While high-intensity statins are generally considered as initial treatment option for secondary prevention, the optimal strategy for CKD patients remains to be clinicaly defined. This study aims to evaluate whether the combination of moderate-intensity statin and ezetimibe is non-inferior to high-intensity statin monotherapy in terms of 3-year composite of major adverse cardiovascular events.

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Key information

Conditions

Renal Insufficiency Arterial Occlusive Diseases Arteriosclerosis Atherosclerosis Cardiovascular Diseases Dyslipidemia Dyslipidemias Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Hypercholesterolemia Hyperlipidemias Kidney Diseases Lipid Metabolism Disorders Male Urogenital Diseases Metabolic Diseases Nutritional and Metabolic Diseases Urogenital Diseases Urologic Diseases Vascular Diseases

Age range

19 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

About this study

All eligible patients with chronic kidney disease (CKD) and concomitant atherosclerotic cardiovascular disease (ASCVD) will be enrolled according to inclusion/exclusion criteria after voluntary agreement with informed consent.

At the time of enrollment, we will stratify the patients according to diabetes mellitus and dialysis status, and randomly assign them in two groups according to lipid-lowering regimen with a 1:1 ratio: "Moderate-intensity statin plus ezetimibe group" vs. "High-intensity statin monotherapy group".

In this study, the combination therapy strategy will utilize Pitavastatin 1-4 mg plus Ezetimibe 10 mg once daily or Atorvastatin 10-20 mg plus Ezetimibe 10 mg once daily. The monotherapy strategy will utilize Atorvastatin 40 mg once daily.

Study visits are scheduled at 4 weeks and at 6, 12, 18, 24, 30, and 36 months. The primary outcome is the composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary outcome is CKD progression defined as a ≥40% decline in eGFR confirmed on at least two consecutive measurements

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 19-85 years.
  • Chronic kidney disease stage III, IV, or V (CKD-EPI eGFR <60 / <30 / <15 mL/min/1.73 m² or on dialysis).
  • Established ASCVD, meeting at least one of the following:
  • Prior acute coronary syndrome (myocardial infarction or unstable angina).
  • Stable angina confirmed by imaging studies.
  • History of coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting).
  • Peripheral artery disease.
  • Ischemic stroke or transient ischemic attack.

Exclusion criteria

  • Baseline LDL cholesterol <55 mg/dL in the absence of statin therapy.
  • Acute liver disease or persistently unexplained serum AST/ALT ≥2 × the upper limit of normal.
  • Allergy or hypersensitivity to statins.
  • Life expectancy <1 year.
  • Expected inability to complete at least 1 year of follow-up.
  • Inability to read or understand the informed consent form.

Treatment and study plan

Moderate-intensity statin and ezetimibe combination therapy

Drug

Participants will receive moderate-intensity statin plus ezetimibe (pitavastatin 1-4 mg + ezetimibe 10 mg once daily or atorvastatin 10-20 mg + ezetimibe 10 mg once daily), with 36-month follow-up.

High-intensity statin monotherapy

Drug

Participants will receive high-intensity statin monotherapy (atorvastatin 40 mg once daily), with 36-month follow-up.

Primary outcomes

  1. Major adverse cardiovascular events

    Time frame: 3 years

    Composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.

Secondary outcomes

  1. CKD progression

    Time frame: 3 years

    CKD progression: ≥40% decline in eGFR from baseline, confirmed on at least two consecutive measurements during follow-up.

  2. Cardiovascular death.

    Time frame: 3 years

    Death due to cardiovascular causes during follow-up.

  3. Myocardial infarction.

    Time frame: 3 years

    Occurrence of myocardial infarction during follow-up.

  4. Stroke.

    Time frame: 3 years

    Occurrence of stroke during follow-up

  5. Hospitalization for unstable angina.

    Time frame: 3 years

    Hospitalization due to unstable angina during follow-up.

  6. Coronary revascularization.

    Time frame: 3 years

    Any coronary revascularization procedure, including percutaneous coronary intervention or coronary artery bypass graft surgery, during follow-up.

  7. Composite of cardiovascular death, myocardial infarction, and stroke.

    Time frame: 3 years

    First occurrence of cardiovascular death, myocardial infarction, or stroke during follow-up.

  8. Composite of cardiovascular death, myocardial infarction, stroke, and hospitalization for unstable angina

    Time frame: 3 years

    First occurrence of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina during follow-up

  9. Composite of cardiovascular death, myocardial infarction, stroke, and coronary revascularization.

    Time frame: 3 years

    First occurrence of cardiovascular death, myocardial infarction, stroke, or coronary revascularization during follow-up.

  10. Composite of all-cause death, myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization.

    Time frame: 3 years

    First occurrence of all-cause death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization during follow-up.

  11. Proportion of participants achieving the LDL-C <70 mg/dL in each group.

    Time frame: 3 years

    Proportion of participants achieving a low-density lipoprotein cholesterol (LDL-C) level below 70 mg/dL in each treatment group during follow-up.

  12. Proportion of participants achieving LDL-C <55 mg/dL in each group.

    Time frame: 3 years

    Proportion of participants achieving a low-density lipoprotein cholesterol (LDL-C) level below 55 mg/dL in each treatment group during follow-up.

  13. Proportion of participants crossing over to the non-assigned treatment group in each group.

    Time frame: 3 years

    Proportion of participants who crossed over from the assigned treatment group to the non-assigned treatment group during follow-up.

  14. New-onset diabetes mellitus.

    Time frame: 3 years

    Occurrence of new-onset diabetes mellitus during follow-up.

  15. New-onset diabetes mellitus requiring initiation of antidiabetic medication.

    Time frame: 3 years

    Occurrence of new-onset diabetes mellitus requiring initiation of antidiabetic medication during follow-up.

  16. Worsening glycemic control.

    Time frame: 3 years

    Occurrence of worsening glycemic control during follow-up

  17. Marked decline in kidney function

    Time frame: 3 years

    eGFR <10 mL/min/1.73 m², confirmed on at least two consecutive measurements during follow-up.

  18. Initiation of dialysis or kidney transplantation.

    Time frame: 3 years

    Initiation of maintenance dialysis or receipt of kidney transplantation during follow-up.

  19. Statin-associated muscle symptoms requiring a change in regimen or dose.

    Time frame: 3 years

    Occurrence of statin-associated muscle symptoms requiring a change in statin regimen or dose during follow-up.

  20. Rhabdomyolysis.

    Time frame: 3 years

    Occurrence of rhabdomyolysis during follow-up.

  21. Elevated creatine phosphokinase (CK >4 × the upper limit of normal)

    Time frame: 3 years

    Elevation of creatine phosphokinase greater than 4 times the upper limit of normal during follow-up.

  22. Elevated liver enzymes (AST and/or ALT ≥3 × the upper limit of normal)

    Time frame: 3 years

    Elevation of aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) equal to or more than 3 times the upper limit of normal during follow-up.

  23. Cancer diagnosis

    Time frame: 3 years

    New diagnosis of cancer during follow-up.

  24. Cataract surgery.

    Time frame: 3 years

    Occurrence of cataract surgery during follow-up.

  25. Hemorrhagic stroke.

    Time frame: 3 years

    Occurrence of hemorrhagic stroke during follow-up.

  26. Major bleeding (BARC type 2, 3, or 5 bleeding), assessed among participants who underwent percutaneous coronary intervention with new stent implantation at study enrollment.

    Time frame: 3 years

    Major bleeding defined as BARC type 2, 3, or 5 bleeding, assessed among participants who underwent percutaneous coronary intervention with new stent implantation at study enrollment.

Study contacts

Contact information is provided by the study sponsor or research team.

Jung-Sun Kim, Professor

CONTACT

[email protected]

+82-2-2228-8460

Sponsors and collaborators

Lead sponsor

Yonsei University

Other

Registry information

Official study title

Utilizing Lipid-lowering Therapy With Moderate-intensity Statin Plus Ezetimibe in Chronic Kidney Disease Patients With Concomitant Atherosclerotic Cardiovascular Disease: ULTRA-CKD Trial

Important dates

Study start
2026
Primary completion
2031
Study completion
2031
First posted
Apr 13, 2026
Registry last updated
Jun 16, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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