Evaluating Finerenone and Empagliflozin for Kidney Function After Nephrectomy

A Multicenter, Open-Label, Factorial Design, Randomized Controlled Study to Explore the Efficacy and Safety of Finerenone and Empagliflozin, Alone or in Combination, in Delaying Renal Function Progression in High-Risk CKD Patients After Radical Nephrectomy for Renal Cell Carcinoma

This study is testing if the medications Finerenone and Empagliflozin can help protect kidney function in people at high risk for chronic kidney disease after having kidney surgery for cancer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jinling Hospital, China (other)
• Drugs / interventions: immunotherapy, radiation
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06818305 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to assess the efficacy and safety of Finerenone and Empagliflozin in delaying the decline of renal function in patients at high risk for chronic kidney disease (CKD) following radical nephrectomy for renal cell carcinoma (RCC). Participants will be randomly assigned to receive either the treatments, a combination of both, or a control group with no drug for one year. The study will monitor renal function and safety profiles through regular clinic visits every three months. The underlying hypothesis is that these medications can mitigate the adverse effects of nephron loss and the resulting compensatory mechanisms that lead to CKD.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with renal tumors scheduled for radical nephrectomy and a moderate to high risk of CKD.

Not a fit: Patients with severe renal impairment or those who do not meet the inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new therapeutic approach to preserve kidney function in patients at high risk for CKD after surgery.

How similar studies have performed: While the specific combination of Finerenone and Empagliflozin in this context is novel, similar studies have shown promise in using these agents for renal protection.

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).

Where this trial is running

Nanjing, Jiangsu

• Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing — Nanjing, Jiangsu, China (RECRUITING)

Study contacts

• Study coordinator: Qu Le M.D

Conditions: Renal Cell Carcinoma, Nephrectomy, Chronic Kidney Disease, Radical Nephrectomy, Renal Functional Compensation, Finerenone, Empagliflozin, Renal Protection