Exploring Approaches With Lower Targets of Blood Pressure and Lipid for Improving Renal Outcome in Advanced Chronic Kidney Disease

NCT ID: NCT06322056

Last Updated: 2024-12-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 642 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-05-13
• Study Completion Date: 2029-08-31

Brief Summary

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.

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.

Conditions

Chronic Kidney Diseases; Hypertension; Dyslipidemias

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intensive SBP control and Intensive LDL-C control

Targeting SBP \<120 mmHg and targeting LDL-C \<70 mg/dL

Group Type: ACTIVE_COMPARATOR

Intensive control of SBP and intensive control of LDL-C

Intervention Type: DRUG

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.

Intensive SBP control and Standard LDL-C control

Targeting SBP \<120 mmHg and targeting LDL-C \<100 mg/dL

Group Type: ACTIVE_COMPARATOR

Intensive control of SBP and standard control of LDL-C

Intervention Type: DRUG

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.

Standard SBP control and Intensive LDL-C control

Targeting SBP \<140 mmHg and targeting LDL-C \<70 mg/dL

Group Type: ACTIVE_COMPARATOR

Standard control of SBP and intensive control of LDL-C

Intervention Type: DRUG

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.

Standard SBP control and Standard LDL-C control

Targeting SBP \<140 mmHg and targeting LDL-C \<100 mg/dL

Group Type: ACTIVE_COMPARATOR

Standard control of SBP and standard control of LDL-C

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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%

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Yonsei University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Severance Hospital

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Seung Hyeok Han

Role: CONTACT

Phone: 82-2-2228-1984

Email: hansh@yuhs.ac

Facility Contacts

Seung Hyeok Han, MD, Ph.D

Role: primary

References

Park CH, Kim HW, Park JT, Chang TI, Yoo TH, Oh KH, Anderson AH, Yang W, Cohen JB, Rahman M, Kang SW, Han SH; on the behalf of CRIC Study and KNOW-CKD Investigators. BP and Kidney Disease Progression in Advanced CKD: Findings from the Chronic Renal Insufficiency Cohort and KoreaN Cohort Study for Outcome in Patients with CKD Studies. Clin J Am Soc Nephrol. 2025 Jun 6;20(9):1179-1189. doi: 10.2215/CJN.0000000760.

Reference Type: DERIVED

PMID: 40478754 (View on PubMed)

Other Identifiers

4-2023-1654

Identifier Type: -

Identifier Source: org_study_id