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This is a multicenter, randomized, double-blind, placebo-controlled clinical trial evaluating the efficacy and safety of finerenone, a nonsteroidal mineralocorticoid receptor antagonist, for the early regression of albuminuria in adults with type 2 diabetes mellitus and chronic kidney disease (eGFR >= 30 mL/min/1.73 m^2 and UACR 30-2000 mg/g) who are already receiving a maximum tolerated dose of an ACE inhibitor or ARB. A total of 148 participants are randomized 1:1, stratified by baseline UACR (<300 vs >=300 mg/g), to oral finerenone (10 or 20 mg once daily, titrated by serum potassium and eGFR) or matching placebo, on top of standard background therapy, for 180 days, followed by a 30-day off-treatment follow-up. Albuminuria regression is defined as both an improvement in Kidney Disease: Improving Global Outcomes albuminuria category, from A3 to A2 or A1, or from A2 to A1, and a more than 30% reduction in urinary albumin-to-creatinine ratio from baseline. The outcome will be reported as the percentage of participants meeting this definition at Day 180.
Background and rationale: Finerenone is an oral, highly selective nonsteroidal mineralocorticoid receptor antagonist approved in China for the treatment of chronic kidney disease associated with type 2 diabetes (with albuminuria). In the phase III FIDELIO-DKD and FIGARO-DKD trials, finerenone added to a maximum tolerated dose of a renin-angiotensin system inhibitor significantly and durably reduced the urine albumin-to-creatinine ratio (UACR) and lowered the risk of kidney and cardiovascular events, with a manageable hyperkalemia risk. A meaningful reduction in albuminuria is an established early surrogate for slowing CKD progression and reducing cardiovascular risk. This study evaluates whether finerenone can achieve early regression of albuminuria in patients with type 2 diabetes and CKD.
Design: This is a multicenter, randomized, double-blind, placebo-controlled trial conducted at up to 12 sites in China. A planned 148 participants are allocated 1:1 to finerenone or matching placebo using central, block randomization (interactive response technology), stratified by baseline UACR (<300 vs >=300 mg/g). Participants and investigators are blinded; placebo tablets are identical in appearance to finerenone, and intervention-period UACR samples are assayed centrally after study completion to preserve blinding.
Population: Eligible participants are adults with type 2 diabetes and CKD (eGFR >= 30 mL/min/1.73 m^2 and UACR 30-2000 mg/g) who have received a maximum tolerated dose of an ACE inhibitor or ARB for at least 90 days and have serum potassium <= 5.0 mmol/L.
Intervention and dose titration: The starting dose is determined by screening eGFR: 10 mg once daily for 30 <= eGFR < 60 mL/min/1.73 m^2, or 20 mg once daily for eGFR >= 60 mL/min/1.73 m^2. The dose is up-titrated to 20 mg, maintained, interrupted, or down-titrated to 10 mg based on serum potassium and eGFR at scheduled and, if needed, unscheduled safety visits. Treatment continues for 180 days.
Visit schedule: a screening period (Day -30 to -1; V1); a treatment period ; and an off-treatment follow-up at Day 210 +/- 5 (V7). Unscheduled safety visits and early-discontinuation visits are performed as needed.
Endpoints: The primary endpoint is the albuminuria regression rate at 180 days, defined as a reduction in UACR KDIGO albuminuria category (A3 to A2 or A1, or A2 to A1) together with a >=30% reduction in UACR from baseline. Secondary endpoints include the change in UACR, the rate of regression to normoalbuminuria, the proportions achieving >=30/40/50% UACR reduction, KDIGO GFR-Albuminuria category improvement, the change in UACR 30 days after discontinuation, the change in eGFR slope, and the change in blood pressure. Safety endpoints include adverse events, serious adverse events, and adverse events of special interest (notably serum potassium changes and hyperkalemia). Exploratory endpoints also included.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Finerenone | Experimental | Finerenone film-coated tablets, orally once daily, on top of standard background therapy. Starting dose determined by screening eGFR: 10 mg if 30 <= eGFR < 60 mL/min/1.73 m^2, or 20 mg if eGFR >= 60 mL/min/1.73 m^2. Dose up-titrated to 20 mg, maintained, interrupted, or down-titrated to 10 mg based on serum potassium and eGFR. Treatment duration 180 days. |
|
| Placebo | Placebo Comparator | Matching placebo tablets identical in appearance to finerenone, orally once daily, on top of standard background therapy, following the same dosing and titration schedule. Treatment duration 180 days. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Finerenone (BAY 94-8862) | Drug | Oral finerenone 10 mg or 20 mg once daily, with dose titration by serum potassium and eGFR, for 180 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Albuminuria regression rate | Proportion of participants achieving albuminuria regression, defined as a reduction in UACR KDIGO albuminuria category (A3 to A2 or A1, or A2 to A1) together with a >=30% reduction in UACR from baseline. | 180 days |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Urinary Albumin-to-Creatinine Ratio | Urinary albumin-to-creatinine ratio will be measured in mg/g. Percent change from baseline will be calculated as: (Day 180 UACR - baseline UACR) / baseline UACR × 100%. | Baseline and 180 days |
| Percentage of Participants With Normoalbuminuria |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Adverse Events | The outcome will be reported as the percentage of participants experiencing at least one adverse event from first dose through the end of the 30-day off-treatment follow-up period. | From first dose through Day 210 |
| Percentage of Participants With Serious Adverse Events |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yuejun Liu | Contact | +8613472844268 | yuejunliu7@126.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The First Affiliated Hospital of Chongqing Medical University | Chongqing | Chongqing Municipality | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24191305 | Background | Heerspink HJ, Gao P, de Zeeuw D, Clase C, Dagenais GR, Sleight P, Lonn E, Teo KT, Yusuf S, Mann JF. The effect of ramipril and telmisartan on serum potassium and its association with cardiovascular and renal events: results from the ONTARGET trial. Eur J Prev Cardiol. 2014 Mar;21(3):299-309. doi: 10.1177/2047487313510678. Epub 2013 Nov 4. | |
| 34059333 |
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Individual participant data will not be shared publicly.
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| Placebo | Drug | Matching placebo tablets, identical in appearance to finerenone, orally once daily, following the same dosing and titration schedule, for 180 days. |
|
Normoalbuminuria is defined as urinary albumin-to-creatinine ratio less than 30 mg/g at Day 180. |
| 180 days |
| Percentage of Participants by UACR Reduction Response Category at Day 180 | Percent reduction in urinary albumin-to-creatinine ratio (UACR) from baseline to Day 180 will be calculated for each participant. Participants will be classified into one of four mutually exclusive UACR reduction response categories: no more than 30% reduction, more than 30% to no more than 40% reduction, more than 40% to no more than 50% reduction, and more than 50% reduction. Participants with no reduction or an increase in UACR will be included in the no more than 30% reduction category. The outcome will be reported as the percentage of participants in each response category. | Baseline to Day 180 |
| Percentage of Participants With Improvement in Kidney Disease: Improving Global Outcomes Albuminuria Category at Day 180 | Improvement in albuminuria category is defined as a change from A3 to A2 or A1, or from A2 to A1, according to Kidney Disease: Improving Global Outcomes urinary albumin-to-creatinine ratio categories. | Baseline to Day 180 |
| Change From Day 180 to Day 210 in Urinary Albumin-to-Creatinine Ratio | Change in urinary albumin-to-creatinine ratio from Day 180 to Day 210 will be assessed in mg/g, corresponding to the 30-day off-treatment follow-up period. | Day 180 to Day 210 |
| Estimated Glomerular Filtration Rate Slope Through Day 180 | Estimated glomerular filtration rate will be calculated using the CKD-EPI equation. The eGFR slope through Day 180 will be estimated from serial eGFR measurements and reported in mL/min/1.73 m2 per year. | Baseline through Day 180 |
| Change From Baseline in Systolic Blood Pressure at Day 180 | Change in systolic blood pressure from baseline to Day 180 will be assessed in mmHg. | Baseline to Day 180 |
| Change From Baseline in Diastolic Blood Pressure at Day 180 | Change in diastolic blood pressure from baseline to Day 180 will be assessed in mmHg. | Baseline to Day 180 |
The outcome will be reported as the percentage of participants experiencing at least one serious adverse event from first dose through the end of the 30-day off-treatment follow-up period. |
| From first dose through Day 210 |
| Adverse events of special interest (AESI) | Including change in serum potassium and incidence of hyperkalemia, incidence of eGFR decline >30% at Day 30, reversibility of eGFR after discontinuation, acute kidney injury, urogenital infection, severe hypoglycemia, symptomatic hypotension, and ketoacidosis | Up to 210 days |
| Change in Composite MRI-PDFF-derived Peri-organ Visceral Fat Fraction | Abdominal magnetic resonance imaging proton density fat fraction will be used to quantify visceral fat fraction (%) in prespecified perirenal, peripancreatic, and perihepatic regions of interest. A composite peri-organ visceral fat fraction will be calculated for each participant as the arithmetic mean of the region-specific MRI-PDFF values from the perirenal, peripancreatic, and perihepatic regions. The outcome will be reported as the percentage-point change in the composite peri-organ visceral fat fraction from baseline to Day 180. | Baseline and 180 days |
| Change in Urine Metabolomic Composite Score | Urine metabolomic features will be measured using a prespecified metabolomics platform. Normalized metabolite feature intensities will be standardized, and a urine metabolomic composite score will be calculated according to the statistical analysis plan. The outcome will be reported as change in composite score from baseline to Day 180. | Baseline to Day 180 |
| Fujian Provincial Hospital | Fuzhou | Fujian | China |
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| Sanshui Hospital, Zhujiang Hospital, Southern Medical University | Foshan | Guangdong | China |
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| Nanfang Hospital, Southern Medical University | Guangzhou | Guangdong | China |
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| Nantong First People's Hospital | Nantong | Jiangsu | China |
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| The First People's Hospital of Suqian | Suqian | Jiangsu | China |
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| Suzhou Science and Technology City Hospital | Suzhou | Jiangsu | China |
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| Xi'an Daxing Hospital | Xi'an | Shaanxi | China |
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| Shanghai Municipal Hospital of Traditional Chinese Medicine | Shanghai | Shanghai Municipality | China |
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| Zhongshan Hospital, Fudan University | Shanghai | Shanghai Municipality | China |
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| The First Affiliated Hospital, Zhejiang University School of Medicine | Hangzhou | Zhejiang | 310003 | China |
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| The First Affiliated Hospital of Ningbo University | Ningbo | Zhejiang | China |
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| The First Affiliated Hospital of Wenzhou Medical University | Wenzhou | Zhejiang | China |
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| Coresh J, Grams ME, Chen TK. Using GFR, Albuminuria, and Their Changes in Clinical Trials and Clinical Care. Am J Kidney Dis. 2021 Sep;78(3):333-334. doi: 10.1053/j.ajkd.2021.04.003. Epub 2021 May 28. No abstract available. |
| 33775708 | Result | Inker LA, Heerspink HJL, Tighiouart H, Chaudhari J, Miao S, Diva U, Mercer A, Appel GB, Donadio JV, Floege J, Li PKT, Maes BD, Locatelli F, Praga M, Schena FP, Levey AS, Greene T. Association of Treatment Effects on Early Change in Urine Protein and Treatment Effects on GFR Slope in IgA Nephropathy: An Individual Participant Meta-analysis. Am J Kidney Dis. 2021 Sep;78(3):340-349.e1. doi: 10.1053/j.ajkd.2021.03.007. Epub 2021 Mar 26. |
| 25887073 | Result | Lambers Heerspink HJ, Gansevoort RT. Albuminuria Is an Appropriate Therapeutic Target in Patients with CKD: The Pro View. Clin J Am Soc Nephrol. 2015 Jun 5;10(6):1079-88. doi: 10.2215/CJN.11511114. Epub 2015 Apr 17. |
| 31473020 | Result | Levey AS, Gansevoort RT, Coresh J, Inker LA, Heerspink HL, Grams ME, Greene T, Tighiouart H, Matsushita K, Ballew SH, Sang Y, Vonesh E, Ying J, Manley T, de Zeeuw D, Eckardt KU, Levin A, Perkovic V, Zhang L, Willis K. Change in Albuminuria and GFR as End Points for Clinical Trials in Early Stages of CKD: A Scientific Workshop Sponsored by the National Kidney Foundation in Collaboration With the US Food and Drug Administration and European Medicines Agency. Am J Kidney Dis. 2020 Jan;75(1):84-104. doi: 10.1053/j.ajkd.2019.06.009. Epub 2019 Aug 28. |
| 30635226 | Result | Heerspink HJL, Greene T, Tighiouart H, Gansevoort RT, Coresh J, Simon AL, Chan TM, Hou FF, Lewis JB, Locatelli F, Praga M, Schena FP, Levey AS, Inker LA; Chronic Kidney Disease Epidemiology Collaboration. Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials. Lancet Diabetes Endocrinol. 2019 Feb;7(2):128-139. doi: 10.1016/S2213-8587(18)30314-0. Epub 2019 Jan 8. |
| 23013602 | Result | Fox CS, Matsushita K, Woodward M, Bilo HJ, Chalmers J, Heerspink HJ, Lee BJ, Perkins RM, Rossing P, Sairenchi T, Tonelli M, Vassalotti JA, Yamagishi K, Coresh J, de Jong PE, Wen CP, Nelson RG; Chronic Kidney Disease Prognosis Consortium. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet. 2012 Nov 10;380(9854):1662-73. doi: 10.1016/S0140-6736(12)61350-6. Epub 2012 Sep 24. |
| 38186886 | Result | Marup FH, Thomsen MB, Birn H. Additive effects of dapagliflozin and finerenone on albuminuria in non-diabetic CKD: an open-label randomized clinical trial. Clin Kidney J. 2023 Sep 26;17(1):sfad249. doi: 10.1093/ckj/sfad249. eCollection 2024 Jan. |
| 40470996 | Result | Agarwal R, Green JB, Heerspink HJL, Mann JFE, McGill JB, Mottl AK, Rosenstock J, Rossing P, Vaduganathan M, Brinker M, Edfors R, Li N, Scheerer MF, Scott C, Nangaku M; CONFIDENCE Investigators. Finerenone with Empagliflozin in Chronic Kidney Disease and Type 2 Diabetes. N Engl J Med. 2025 Aug 7;393(6):533-543. doi: 10.1056/NEJMoa2410659. Epub 2025 Jun 5. |
| 38048573 | Result | Agarwal R, Tu W, Farjat AE, Farag YMK, Toto R, Kaul S, Lawatscheck R, Rohwedder K, Ruilope LM, Rossing P, Pitt B, Filippatos G, Anker SD, Bakris GL; FIDELIO-DKD and FIGARO-DKD Investigators. Impact of Finerenone-Induced Albuminuria Reduction on Chronic Kidney Disease Outcomes in Type 2 Diabetes : A Mediation Analysis. Ann Intern Med. 2023 Dec;176(12):1606-1616. doi: 10.7326/M23-1023. Epub 2023 Dec 5. |
| 35023547 | Result | Agarwal R, Filippatos G, Pitt B, Anker SD, Rossing P, Joseph A, Kolkhof P, Nowack C, Gebel M, Ruilope LM, Bakris GL; FIDELIO-DKD and FIGARO-DKD investigators. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022 Feb 10;43(6):474-484. doi: 10.1093/eurheartj/ehab777. |
| 34449181 | Result | Pitt B, Filippatos G, Agarwal R, Anker SD, Bakris GL, Rossing P, Joseph A, Kolkhof P, Nowack C, Schloemer P, Ruilope LM; FIGARO-DKD Investigators. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. N Engl J Med. 2021 Dec 9;385(24):2252-2263. doi: 10.1056/NEJMoa2110956. Epub 2021 Aug 28. |
| 33264825 | Result | Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P, Kolkhof P, Nowack C, Schloemer P, Joseph A, Filippatos G; FIDELIO-DKD Investigators. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med. 2020 Dec 3;383(23):2219-2229. doi: 10.1056/NEJMoa2025845. Epub 2020 Oct 23. |
| Result | 中华医学会糖尿病学分会, 国家基层公共卫生服务项目基础糖尿病防治管理办公室. 国家基层糖 尿病肾脏病防治技术指南 (2023). 中华内科杂志, 2023, 62(12): 1394-1405 |
| 38078592 | Result | American Diabetes Association Professional Practice Committee. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2024. Diabetes Care. 2024 Jan 1;47(Suppl 1):S179-S218. doi: 10.2337/dc24-S010. |
| 31492486 | Result | Yang C, Wang H, Zhao X, Matsushita K, Coresh J, Zhang L, Zhao MH. CKD in China: Evolving Spectrum and Public Health Implications. Am J Kidney Dis. 2020 Aug;76(2):258-264. doi: 10.1053/j.ajkd.2019.05.032. Epub 2019 Sep 3. |
| 34962526 | Result | Wang L, Peng W, Zhao Z, Zhang M, Shi Z, Song Z, Zhang X, Li C, Huang Z, Sun X, Wang L, Zhou M, Wu J, Wang Y. Prevalence and Treatment of Diabetes in China, 2013-2018. JAMA. 2021 Dec 28;326(24):2498-2506. doi: 10.1001/jama.2021.22208. |
| Result | IDF ATLAS REPORTS: Diabetes and Kidney Disease- 2023. www.diabetesatlas.org |
| ID | Term |
|---|---|
| D000419 | Albuminuria |
| D003924 | Diabetes Mellitus, Type 2 |
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D011507 | Proteinuria |
| D014555 | Urination Disorders |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| C576501 | finerenone |
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