Efficacy and Safety of Finerenone and Empagliflozin in Delaying Renal Function Progression After Radical Nephrectomy in High-Risk CKD Patients: a Multicenter RCT

Launched by JINLING HOSPITAL, CHINA · Feb 4, 2025

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ClinConnect Summary

This clinical trial is investigating whether two medications, Finerenone and Empagliflozin, can help slow down kidney function decline in patients who are at high risk for chronic kidney disease (CKD) after having surgery to remove a kidney tumor, specifically for kidney cancer. Researchers want to find out if these treatments, either alone or together, are effective and safe for patients who have undergone a radical nephrectomy (surgery to remove the entire kidney).

To be eligible for this trial, participants must be at least 18 years old, scheduled for kidney surgery due to a tumor, and have certain medical criteria indicating they are at moderate to high risk for CKD. Participants will take the medications or a placebo (a pill with no active drug) daily for one year and will visit the clinic every three months for check-ups and tests. They will also keep a diary to track any health changes. This study is currently looking for volunteers, and it's important for interested individuals to discuss their eligibility with their healthcare provider.

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Eligibility criteria

• Inclusion Criteria:
• • 1、Voluntary participation in the study and signing of the informed consent form, with the ability to comply with the study or follow-up procedures.
• • 2、Age ≥ 18 years (at the time of signing the informed consent form), regardless of sex.
• • 3、Patients with renal tumors (T1-T2) who are scheduled to undergo radical nephrectomy; no specific surgical procedure requirements.
• • 4、Normal imaging of the healthy kidney at screening. 5、csCKD score ≥ 7 (moderate risk: 7-8 points; high risk: 9-10 points). 6、Preoperative difference in renal function of \<10% (healthy kidney function - affected kidney function).
• • 7、Serum potassium ≤ 5.0 mmol/L. 8、Urinary albumin-to-creatinine ratio (UACR) \< 30 mg/g (3 mg/mmol). 9、ECOG performance status score of 0-2. 10、Normal cardiovascular, pulmonary, and liver function. 11、Women of non-reproductive potential are not required to undergo pregnancy testing or provide consent for appropriate contraceptive use. Non-reproductive potential is defined as women who have undergone hysterectomy, bilateral salpingectomy, oophorectomy, or are postmenopausal (with no other medical reasons for amenorrhea for 12 months).
• • 12、Women of reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to enrollment, and must agree to use appropriate contraception during the study and for 8 weeks after the last dose of study intervention. Appropriate contraception is defined as an intrauterine device (IUD) or physical barriers (e.g., condoms)
• Exclusion Criteria:
• * Patients who meet any of the following conditions:
• • 1. Preoperative eGFR \< 60 mL/min/1.73m² (calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation).
• • 2. eGFR of the healthy kidney \< 30 mL/min/1.73m².
• • 3. Type 1 diabetes (T1D) or diabetic ketoacidosis.
• • 4. Pregnant or breastfeeding women.
• • 5. Patients with a desire to conceive during the study period or within 2 months after the study; male patients planning to conceive or donate sperm during the study period or within 3 months after the study.
• • 6. Body mass index (BMI) \< 18.5 kg/m² or \> 30 kg/m².
• • 7. Previous or concurrent participation in another clinical study (≤30 days before randomization).
• • 8. Communication disorders preventing full understanding or cooperation, or poor compliance.
• * Patients with the following medical or surgical history:
• • 1. Urological structural abnormalities or unresolved functional abnormalities (e.g., duplicated kidney, polycystic kidney, horseshoe kidney, solitary kidney, renal artery stenosis, urinary tract obstruction, kidney stones, benign prostatic hyperplasia, prostatitis, or previous kidney surgery, etc.), long-term catheterization, etc.
• • 2. History of or planned kidney replacement therapy (dialysis or kidney transplant) within 12 weeks or kidney transplant planned within 12 months.
• • 3. Uncontrolled blood glucose: HbA1c ≥ 12%.
• • 4. Uncontrolled blood pressure: Initial or follow-up seated systolic blood pressure (SBP) ≥ 180 mmHg or seated diastolic blood pressure (DBP) ≥ 110 mmHg, or symptomatic hypotension and/or systolic blood pressure \< 90 mmHg, or clinically judged hypovolemic patients.
• • 5. Previous radiation therapy or ablation therapy to the healthy kidney or other surgical procedures.
• • 6. History of heart failure (NYHA Class III-IV) or hospitalization due to fluid retention.
• • 7. Clinical history of cerebrovascular disease (transient ischemic attack or stroke) or coronary artery disease (hospitalization for myocardial infarction or unstable angina, new-onset angina, or coronary angiography showing stenosis, coronary artery revascularization) within the last 6 months.
• • 8. History of pulmonary hypertension, pulmonary fibrosis, or any lung condition requiring oxygen therapy (e.g., chronic obstructive pulmonary disease, emphysema).
• • 9. Severe peripheral edema or facial edema within 4 weeks of screening, requiring diuretic treatment, or history of myxedema.
• • 10. Liver function impairment, with any of the following: history of hepatic encephalopathy, esophageal varices, portal vein shunt surgery, severe liver dysfunction (Child-Pugh Class C), ALT or AST \> 3 times the upper limit of normal (ULN), or total bilirubin \> 2 times the ULN at screening.
• • 11. Primary adrenal insufficiency (Addison's disease).
• • 12. Recurrent urinary tract infections within the past 6 months.
• • 13. Organ or bone marrow transplant history.
• • 14. History of malignancy, except for those with: cured or in remission for ≥5 years, or radically excised basal cell carcinoma, squamous cell carcinoma, or any in situ carcinoma at any site.
• • 15. Received cytotoxic drugs, immunosuppressive therapy, or other immunotherapy for primary or secondary kidney disease within the last 6 months.
• • 16. Hematocrit ≤ 30%.
• • 17. Conditions that may significantly affect drug absorption, distribution, metabolism, or excretion, including but not limited to: 1) active inflammatory bowel disease in the last 6 months; 2) history of gastric surgery (e.g., gastrectomy, gastrointestinal anastomosis, or bowel resection); 3) history of gastrointestinal ulcers and/or gastrointestinal or rectal bleeding in the last 6 months; 4) history of pancreatic injury or pancreatitis in the last 6 months.
• • 18. Other complex medical conditions that may interfere with the study behavior or increase risks, such as organ failure, immunodeficiency diseases or HIV-positive status, viral hepatitis, cognitive disorders, or severe physical or mental illnesses.
• • 19. Any disease with a life expectancy of less than 12 months.
• • 20. Known allergy to the study drug or any drugs with a similar chemical structure or excipients. Note: Finerenone contains lactose; patients with galactose intolerance or malabsorption, or lactase deficiency are contraindicated.
• * Current or past use of the following medications:
• • 1. Currently using potassium-sparing diuretics (e.g., amiloride, triamterene), other mineralocorticoid receptor antagonists (e.g., eplerenone, esaxerenone, spironolactone, canrenone), and unable to stop the medication ≥ 4 weeks before screening.
• • 2. Strong CYP3A4 inhibitors or inducers (e.g., itraconazole, ketoconazole, ritonavir, nelfinavir, cobicistat, telithromycin, naftifine, or grapefruit/grapefruit juice), and unable to stop at least 7 days before randomization.
• • 3. Currently receiving systemic treatment for malignancy.
• • 4. History of drug or alcohol abuse within the last 12 months.
• • 5. Received Empagliflozin treatment within 8 weeks prior to dosing or known intolerance to Empagliflozin.
• • 6. Received Finerenone treatment within 12 months prior to dosing.
• • 7. Kidney transplant patients or those on high-dose steroids or immunosuppressive therapy (e.g., systemic lupus erythematosus, ANCA-associated vasculitis, glomerulonephritis, nephrotic syndrome).