Exploring Approaches With Lower Targets of Blood Pressure and Lipid for Improving Renal Outcome in Advanced Chronic Kidney Disease (EXCELSIOR-CKD)

The purpose of this study is to prevent kidney disease progression in adults with advanced chronic kidney disease (estimated glomerular filtration rate [eGFR] between 15-45 mL/min/1.73 m2) using intensive blood pressure control and intensive lipid management with 2X2 factorial design.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Chronic Kidney Diseases; Dyslipidemias
• Intervention / Treatment: Drug: Intensive control of SBP and intensive control of LDL-C; Drug: Intensive control of SBP and standard control of LDL-C; Drug: Standard control of SBP and intensive control of LDL-C; Drug: Standard control of SBP and standard control of LDL-C

Detailed Description

The EXploring approaChEs with Lower targets of blood preSsure and lIpid for impOving Renal outcome in advanced Chronic Kidney Disease (EXCELSIOR-CKD) strived to enroll about 642 participants aged ≥19 years with eGFR 15-45 mL/min/1.73 m2, systolic blood pressure (SBP) ≥130 mmHg, and low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL.

The EXCELSIOR-CKD study is a 2X2 factorial design with factors consisting of: intensive versus standard SBP control (120 vs 140 mmHg), and intensive versus standard LDL-C control (70 vs 100 mg/dL).

The primary hypothesis was that kidney disease progression event rates would be lower in the intensive arms. Participants would be recruited at 13 clinics over approximately a 2-year period, and are planned to be followed for 3 years.

• Study Type: Interventional
• Enrollment (Estimated): 642
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Seung Hyeok Han; Phone Number: 82-2-2228-1984; Email: hansh@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
    • Contact: Seung Hyeok Han, MD, Ph.D; Phone Number: 82-2-2228-1984; Email: hansh@yuhs.ac

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Fulfillment of all of followings

  1. At least 19 years old
  2. Evidence of CKD defined at least 3 months before and at the time of screening visit with CKD-EPI eGFR ≥15 to <45 mL/min/1.73 m2

  3. SBP of

     • 130-180 mmHg on 0 or 1 medication
     • 130-170 mmHg on upto 2 medications
     • 130-160 mmHg on more than 3 medications
  4. LDL-C ≥100 mg/dL

Exclusion Criteria:

• Any of followings

  1. Resistant hypertension or poorly controlled hypertension

     • Failure to achieve SBP of <140 mmHg despite using 4 or more antihypertensive medications including diuretics
  2. Known secondary cause of hypertension
  3. History of renal devervation procedure
  4. Glomerulonephritis requiring immunosuppresive agents
  5. Autosomal dominant polycystic kidney disease receiving tolvaptan
  6. CKD-EPI < 15 mL/min/1.73 m2 or receiving kidney replacement therapy
  7. Familial hypercholesterolemia
  8. Cardiovascular event or precedure (as defined as myocardial infarction, unstable angina, coronary revascularization, or stroke) within last 3 months or planning to cardiovascular procedure upcoming 3 months at the time of screening visit
  9. Symptomatic heart failure within 6 months of left ventricular ejection fraction <45%
  10. A medical condition likely to limit survival to less thant 3 years
  11. Diagnosis of malignancy within the last 5 years or undergoing chemotherepy or radiotherapy
  12. Any organ transplant
  13. Advanced cirrhosis (Child-Pugh class B or C) or abnormal liver function test (alanine transaminase or aspartate transaminase ≥1.5 X upper normal limit)
  14. Evidence of active inflammatory muscle disease (polymyositis or dermatomyositis) or creatine kinase elevation (≥3 X upper normal limit)
  15. History of adverse reaction to HMG-CoA reductase inhibitors or ezetimibe

  16. Using any drugs as followings:

      • Nicotinic acid
      • Macrolide antibiotics
      • Systemic imidazole or triazole antifungal agent
      • Protease inhibitor
      • Nefazodone
      • Immunosuppressive agents (glucocorticoid [equivalent to prednisone 10 mg/day over 4 weeks], cyclosporin, mycofenolate, azathioprine, methotrexate, cyclophosphamide, or rituximab)
  17. Pregnancy or trying to become pregnant
  18. Diabetes mellitus, type I
  19. Diabetes mellitus, type II with HbA1c ≥10.0%

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intensive SBP control and Intensive LDL-C control; Targeting SBP <120 mmHg and targeting LDL-C <70 mg/dL	Drug: Intensive control of SBP and intensive control of LDL-C; Eligible participants would be assigned to a SBP target of less than 120 mmHg and a LDL-C target of less than 70 mg/dL.
Active Comparator: Intensive SBP control and Standard LDL-C control; Targeting SBP <120 mmHg and targeting LDL-C <100 mg/dL	Drug: Intensive control of SBP and standard control of LDL-C; Eligible participants would be assigned to a SBP target of less than 120 mmHg and a LDL-C target of less than 100 mg/dL.
Active Comparator: Standard SBP control and Intensive LDL-C control; Targeting SBP <140 mmHg and targeting LDL-C <70 mg/dL	Drug: Standard control of SBP and intensive control of LDL-C; Eligible participants would be assigned to a SBP target of less than 140 mmHg and a LDL-C target of less than 70 mg/dL.
Active Comparator: Standard SBP control and Standard LDL-C control; Targeting SBP <140 mmHg and targeting LDL-C <100 mg/dL	Drug: Standard control of SBP and standard control of LDL-C; Eligible participants would be assigned to a SBP target of less than 140 mmHg and a LDL-C target of less than 100 mg/dL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal composite outcome	Renal composite outcome would be defined as one of followings: A sustained decline in eGFR of 40%,; Initiation of kidney replacement therapy (dialysis or kidney transplantation),; A sustained eGFR <10 mL/min/1.73 m2, or; Death from renal causes	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Individual components of renal composite outcome	A sustained decline in eGFR of 40%; Initiation of kidney replacement therapy (dialysis or kidney transplantation),; A sustained eGFR <10 mL/min/1.73 m2; Death from renal causes; Rate of change of eGFR during chronic phase I (12 week to 3 year); Rate of change of eGFR during chronic phase II (24 week to 3 year); Rate of change of eGFR during study period (0 week to 3 year); Cardiovascular composite outcome (defined as one of followings):Death from cardiovascular causes,Non-fatal myocardial infarction,Non-fatal stroke (ischemic or hemorrhagic),Hospitalization for heart failure, orRevascularization (coronary, carotid, or peripheral artery)	up to 3 years
eGFR slopes	A sustained decline in eGFR of 40%; Initiation of kidney replacement therapy (dialysis or kidney transplantation),; A sustained eGFR <10 mL/min/1.73 m2; Death from renal causes; Rate of change of eGFR during chronic phase I (12 week to 3 year); Rate of change of eGFR during chronic phase II (24 week to 3 year); Rate of change of eGFR during study period (0 week to 3 year); Cardiovascular composite outcome (defined as one of followings):Death from cardiovascular causes,Non-fatal myocardial infarction,Non-fatal stroke (ischemic or hemorrhagic),Hospitalization for heart failure, orRevascularization (coronary, carotid, or peripheral artery)	up to 3 years
Cardiovascular composite outcome	A sustained decline in eGFR of 40%; Initiation of kidney replacement therapy (dialysis or kidney transplantation),; A sustained eGFR <10 mL/min/1.73 m2; Death from renal causes; Rate of change of eGFR during chronic phase I (12 week to 3 year); Rate of change of eGFR during chronic phase II (24 week to 3 year); Rate of change of eGFR during study period (0 week to 3 year); Cardiovascular composite outcome (defined as one of followings):Death from cardiovascular causes,Non-fatal myocardial infarction,Non-fatal stroke (ischemic or hemorrhagic),Hospitalization for heart failure, orRevascularization (coronary, carotid, or peripheral artery)	up to 3 years

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2024
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): August 31, 2029

Study Registration Dates

• First Submitted: March 13, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Metabolic Diseases; Renal Insufficiency; Lipid Metabolism Disorders; Kidney Diseases; Renal Insufficiency, Chronic; Dyslipidemias
• Other Study ID Numbers: 4-2023-1654

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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