Moderate-Intensity Statin Plus Ezetimibe in CKD and ASCVD

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular Diseases; Renal Insufficiency; Atherosclerosis; Dyslipidemia; Hypercholesterolemia
• Intervention / Treatment: Drug: High-intensity statin monotherapy; Drug: Moderate-intensity statin and ezetimibe combination therapy

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 1952
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jung-Sun Kim, Professor; Phone Number: +82-2-2228-8460; Email: kjs1218@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 19-85 years.
2. Chronic kidney disease stage III, IV, or V (CKD-EPI eGFR <60 / <30 / <15 mL/min/1.73 m² or on dialysis).

3. 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:

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Moderate-intensity statin and ezetimibe combination therapy; 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.	Drug: Moderate-intensity statin and ezetimibe combination therapy; 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.
Active Comparator: High-intensity statin monotherapy; Participants will receive high-intensity statin monotherapy (atorvastatin 40 mg once daily), with 36-month follow-up.	Drug: High-intensity statin monotherapy; Participants will receive high-intensity statin monotherapy (atorvastatin 40 mg once daily), with 36-month follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse cardiovascular events	Composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CKD progression	CKD progression: ≥40% decline in eGFR from baseline, confirmed on at least two consecutive measurements during follow-up.	3 years
Cardiovascular death.	Death due to cardiovascular causes during follow-up.	3 years
Myocardial infarction.	Occurrence of myocardial infarction during follow-up.	3 years
Stroke.	Occurrence of stroke during follow-up	3 years
Hospitalization for unstable angina.	Hospitalization due to unstable angina during follow-up.	3 years
Coronary revascularization.	Any coronary revascularization procedure, including percutaneous coronary intervention or coronary artery bypass graft surgery, during follow-up.	3 years
Composite of cardiovascular death, myocardial infarction, and stroke.	First occurrence of cardiovascular death, myocardial infarction, or stroke during follow-up.	3 years
Composite of cardiovascular death, myocardial infarction, stroke, and hospitalization for unstable angina	First occurrence of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina during follow-up	3 years
Composite of cardiovascular death, myocardial infarction, stroke, and coronary revascularization.	First occurrence of cardiovascular death, myocardial infarction, stroke, or coronary revascularization during follow-up.	3 years
Composite of all-cause death, myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization.	First occurrence of all-cause death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization during follow-up.	3 years
Proportion of participants achieving the LDL-C <70 mg/dL in each group.	Proportion of participants achieving a low-density lipoprotein cholesterol (LDL-C) level below 70 mg/dL in each treatment group during follow-up.	3 years
Proportion of participants achieving LDL-C <55 mg/dL in each group.	Proportion of participants achieving a low-density lipoprotein cholesterol (LDL-C) level below 55 mg/dL in each treatment group during follow-up.	3 years
Proportion of participants crossing over to the non-assigned treatment group in each group.	Proportion of participants who crossed over from the assigned treatment group to the non-assigned treatment group during follow-up.	3 years
New-onset diabetes mellitus.	Occurrence of new-onset diabetes mellitus during follow-up.	3 years
New-onset diabetes mellitus requiring initiation of antidiabetic medication.	Occurrence of new-onset diabetes mellitus requiring initiation of antidiabetic medication during follow-up.	3 years
Worsening glycemic control.	Occurrence of worsening glycemic control during follow-up	3 years
Marked decline in kidney function	eGFR <10 mL/min/1.73 m², confirmed on at least two consecutive measurements during follow-up.	3 years
Initiation of dialysis or kidney transplantation.	Initiation of maintenance dialysis or receipt of kidney transplantation during follow-up.	3 years
Statin-associated muscle symptoms requiring a change in regimen or dose.	Occurrence of statin-associated muscle symptoms requiring a change in statin regimen or dose during follow-up.	3 years
Rhabdomyolysis.	Occurrence of rhabdomyolysis during follow-up.	3 years
Elevated creatine phosphokinase (CK >4 × the upper limit of normal)	Elevation of creatine phosphokinase greater than 4 times the upper limit of normal during follow-up.	3 years
Cancer diagnosis	New diagnosis of cancer during follow-up.	3 years
Cataract surgery.	Occurrence of cataract surgery during follow-up.	3 years
Hemorrhagic stroke.	Occurrence of hemorrhagic stroke during follow-up.	3 years
Major bleeding (BARC type 2, 3, or 5 bleeding), assessed among participants who underwent percutaneous coronary intervention with new stent implantation at study enrollment.	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.	3 years
Elevated liver enzymes (AST and/or ALT ≥3 × the upper limit of normal)	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.	3 years

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): January 22, 2031
• Study Completion (Estimated): January 22, 2031

Study Registration Dates

• First Submitted: April 3, 2026
• First Submitted That Met QC Criteria: April 3, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 17, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Hyperlipidemias; Lipid Metabolism Disorders; Arteriosclerosis; Arterial Occlusive Diseases; Nutritional and Metabolic Diseases; Cardiovascular Diseases; Hypercholesterolemia; Renal Insufficiency; Dyslipidemias; Atherosclerosis
• Other Study ID Numbers: 4-2025-1647

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No