Investigation on the Impact of Finerenone on Myocardial Remodeling in Patients With Diabetic Kidney Disease and Heart Failure

Обзор

The goal of this clinical trial is to evaluate the impact of Finerenone on myocardial remodeling in patients with diabetic kidney disease (DKD) and heart failure with a left ventricular ejection fraction (LVEF) ≥ 40%. The main questions it aims to answer are: 1. Does 6-month treatment with Finerenone significantly reduce myocardial fat infiltration (measured by MR Spectroscopy) and myocardial fibrosis (measured by extracellular volume fraction on CMR)? 2. Does Finerenone improve global left ventricular longitudinal systolic strain (GLS) and other structural remodeling indices in this patient population? Researchers will compare cardiac imaging parameters after 6 months of treatment to baseline values to see if Finerenone effectively reverses or slows down pathological cardiac changes. Participants will: 1. Take Finerenone (Kerendia) 10 mg or 20 mg orally once daily for a total of 6 months. 2. Undergo advanced cardiac imaging, including Cardiac Magnetic Resonance (CMR) and MR Spectroscopy (MRS), at the beginning of the study and after 6 months of treatment. 3. Receive regular clinical follow-up and blood tests to monitor safety (such as potassium levels and kidney function) and treatment efficacy.

Подробное описание

I. Research Objectives This study is a prospective, open-label, single-arm cardiac imaging trial. It focuses on patients with diabetic kidney disease (DKD) and heart failure with a left ventricular ejection fraction (LVEF) ≥ 40%. The objective is to quantitatively evaluate the changes in myocardial fat infiltration, myocardial fibrosis (Extracellular Volume fraction, ECV), global left ventricular longitudinal systolic strain (GLS), and other myocardial remodeling indices using advanced imaging techniques-Cardiac Magnetic Resonance (CMR) and MR Spectroscopy (MRS)-following 6 months of Finerenone treatment.

II. Research Background Mineralocorticoid receptor (MR) activation is considered a key factor in the pathophysiological mechanism of heart failure. MR activation triggers downstream intracellular signaling, leading to sodium and water retention, systemic hypertension, endothelial dysfunction, as well as pathological fibrosis, hypertrophy, and inflammatory responses in both the heart and kidneys. Conventional mineralocorticoid receptor antagonists (MRAs), such as Spironolactone and Eplerenone, have been proven to improve survival rates and clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF, LVEF \< 40%). However, the efficacy and role of MRAs in non-systolic heart failure, particularly heart failure with preserved ejection fraction (HFpEF), remain controversial.

Post-hoc analysis of the TOPCAT trial indicated that Spironolactone could reduce the risk of heart failure hospitalization and cardiovascular death in HFpEF patients, but it was accompanied by side effects such as hyperkalemia and worsening renal function. Finerenone is a next-generation non-steroidal MRA with higher MR selectivity and a balanced tissue distribution between the heart and kidneys. Clinical studies have shown that compared to Spironolactone, Finerenone carries a lower risk of inducing hyperkalemia and renal function impairment in patients with chronic kidney disease (CKD). Finerenone has been approved by the U.S. FDA and Taiwan TFDA for use in patients with type 2 diabetes and chronic kidney disease to delay the progression of renal failure and reduce cardiovascular risks. The FINEARTS-HF multinational, multicenter, phase 3 clinical trial published in 2024 was the first to evaluate Finerenone in heart failure patients with LVEF \> 40% (including both mildly reduced and preserved ejection fraction). The results showed that Finerenone significantly reduced the risk of worsening heart failure events and cardiovascular death; however, the underlying pathophysiological mechanisms are not yet fully elucidated, necessitating further research. The study drug, Finerenone (trade name: Kerendia®, Taiwan FDA No. 028326), is approved and marketed in Europe, the United States, and Taiwan, with a dosage of once-daily oral administration. Kerendia® is currently indicated for the treatment of chronic kidney disease associated with type 2 diabetes, effectively slowing the decline in glomerular filtration rate (eGFR) and reducing the risks of cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure.

Myocardial remodeling, especially left ventricular remodeling, refers to the structural and functional changes triggered by myocardial injury and hemodynamic alterations during the progression of heart failure. Improvements in left ventricular remodeling are closely linked to patient prognosis. In clinical practice, conventional echocardiography is commonly used to assess indices such as left ventricular internal diameter, ejection fraction, and diastolic function (e.g., E/e' ratio). However, its sensitivity is often insufficient to detect early myocardial functional changes in patients with heart failure with mildly reduced or preserved ejection fraction. This study utilizes advanced imaging techniques-Cardiac Magnetic Resonance (CMR) and MR Spectroscopy (MRS)-to further quantitatively assess the degree of myocardial fat infiltration and myocardial fibrosis. Therefore, this study aims to explore the effects of Finerenone treatment on myocardial fat infiltration, myocardial fibrosis, GLS, and other myocardial remodeling indicators in DKD patients with heart failure and LVEF ≥ 40%, while further analyzing the correlation between these changes and clinical prognosis.

III. Research Design and Process This is a domestic multicenter, prospective, open-label, single-arm cardiac imaging study. The study focuses on DKD patients with heart failure and LVEF ≥ 40%. It compares and quantitatively evaluates the degree of myocardial fat infiltration and myocardial fibrosis utilizing Cardiac Magnetic Resonance (CMR) and MR Spectroscopy (MRS) after 6 months of Finerenone treatment.

Вмешательства

• Препарат Finerenone
  Finerenone is a non-steroidal, selective mineralocorticoid receptor antagonist (MRA). In this study, participants will receive Finerenone in tablet form, administered orally once daily for a duration of 6 months. The dosage (10 mg or 20 mg) will be determined and adjusted according to the participant's baseline estimated glomerular filtration rate (eGFR) and serum potassium levels, following the approved clinical guidelines.

Первичные конечные точки

• Change from baseline in Myocardial Extracellular Volume fraction (ECV) [Срок оценки: Baseline and 6 months]

Критерии участия

Критерии включения

• 1\. \*\*Age and Consent:\*\*
• Age ≥ 18 years at the time of signing informed consent.
• Capable of giving signed informed consent and willing to comply with all study requirements and restrictions.
• 2\. \*\*Type 2 Diabetes and Chronic Kidney Disease (CKD):\*\*
• Diagnosis of Type 2 Diabetes Mellitus with chronic kidney disease, defined by either:
• Urine albumin-to-creatinine ratio (UACR) 30 to 300 mg/g AND estimated glomerular filtration rate (eGFR) 25 to 90 mL/min/1.73 m², OR
• UACR ≥ 300 mg/g AND eGFR ≥ 60 mL/min/1.73 m².
• 3\. \*\*Heart Failure Status:\*\*
• Clinical diagnosis of Heart Failure (NYHA Class II to IV) currently receiving inpatient or outpatient treatment.
• Diagnosis must be confirmed by meeting at least 2 \*\*Major Criteria\*\* OR 1 \*\*Major Criterion\*\* plus 2 \*\*Minor Criteria\*\* (Framingham Criteria):
• \*\*Major Criteria:\*\* Orthopnea or paroxysmal nocturnal dyspnea; Jugular venous distension; Hepatojugular reflux; Pulmonary rales; Third heart sound (S3) gallop; Pulmonary edema; Cardiomegaly.
• \*\*Minor Criteria:\*\* Decreased exercise tolerance; Night cough; Dependent (ankle) edema; Tachycardia (heart rate > 120 bpm); Hepatomegaly; Pleural effusion.
• 4\. \*\*Left Ventricular Function:\*\*
• Documented Left Ventricular Ejection Fraction (LVEF) ≥ 40% measured by transthoracic echocardiography within the last 12 months.
• 5\. \*\*Structural Heart Disease:\*\*
• Confirmed by echocardiography, meeting at least one of the following findings:
• LV mass index ≥ 95 g/m² in females or ≥ 115 g/m² in males.
• Left atrial (LA) volume index > 29 mL/m² (for sinus rhythm) or > 40 mL/m² (for atrial fibrillation).
• Average E/e' ratio > 14.
• Tricuspid regurgitation (TR) velocity > 2.8 m/s.
• 6\. \*\*Elevated Biomarkers:\*\*
• Elevated NT-proBNP levels within 90 days prior to enrollment:
• NT-proBNP ≥ 300 pg/mL for participants in sinus rhythm.
• NT-proBNP ≥ 600 pg/mL for participants with atrial fibrillation.
• 7\. \*\*Reproductive Status:\*\*
• Women of childbearing potential must have a negative pregnancy test and agree to use highly effective contraception during the study.

Критерии исключения

• 1\. \*\*Renal and Electrolyte Stability:\*\*
• eGFR < 25 mL/min/1.73 m² (One re-evaluation is permitted prior to enrollment).
• Serum potassium > 5.0 mmol/L at any screening or enrollment visit (One re-evaluation is permitted prior to enrollment).
• 2\. \*\*Recent Cardiovascular Events (within 90 days prior to enrollment):\*\*
• Acute inflammatory heart disease (e.g., acute myocarditis).
• Myocardial infarction or any event likely to reduce ejection fraction.
• Coronary artery bypass graft (CABG) surgery or Percutaneous Coronary Intervention (PCI).
• Stroke or Transient Ischemic Attack (TIA).
• 3\. \*\*Comorbidities Mimicking Heart Failure:\*\*
• Severe COPD requiring home oxygen therapy or chronic oral steroid therapy.
• Primary pulmonary hypertension.
• Hemoglobin < 10 g/dL.
• Clinically significant valvular heart disease.
• Body Mass Index (BMI) > 50 kg/m².
• 4\. \*\*Hemodynamic and Rhythm Instability:\*\*
• Uncontrolled hypertension (SBP ≥ 160 mmHg on ≥ 3 drugs, or SBP ≥ 180 mmHg regardless of treatment).
• Uncontrollable arrhythmia (Sustained VT, or AF/Flutter with resting HR > 110 bpm).
• Symptomatic hypotension or mean SBP < 90 mmHg.
• 5\. \*\*Specific Cardiomyopathies and Devices:\*\*
• Peripartum, chemotherapy-induced, viral, or infiltrative cardiomyopathy.
• Constrictive pericarditis or hereditary hypertrophic cardiomyopathy.
• Right heart failure not caused by left heart failure.
• Use of a Left Ventricular Assist Device (LVAD).
• 6\. \*\*Surgery and Acute Support:\*\*
• Planned surgery for heart failure-related etiologies (e.g., severe AS or MR).
• Use of IV vasodilators, IV inotropes, or mechanical hemodynamic support (e.g., IABP, ECMO, mechanical ventilation) within 24 hours prior to enrollment.
• 7\. \*\*Medication and Safety Concerns:\*\*
• History of hyperkalemia or acute renal failure resulting in discontinuation of MRA treatment lasting more than 7 days.
• Previous or continuous use (≥ 90 days) of MRAs within 12 months prior to enrollment.
• Inability to discontinue renin inhibitors or potassium-sparing diuretics (other than Finerenone).
• Concurrent use of strong CYP3A4 inhibitors or moderate/strong CYP3A4 inducers within 7 days prior to enrollment.
• Known hypersensitivity to Finerenone or its excipients.
• 8\. \*\*General Health and Other Exclusions:\*\*
• Pregnant or breastfeeding women.
• Hepatic impairment classified as Child-Pugh C.
• Addison's disease (primary adrenocortical insufficiency).
• Life expectancy < 12 months (e.g., active malignancy).
• Participation in other interventional clinical trials within 30 days prior to enrollment.
• Close relationship with the study site or investigators.
• Current alcohol or illicit drug abuse.
• Legal detention or incarceration.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Тайвань · 1 центр

• Cathay General Hospital — Taipei

Публикации

• Su MY, Lin LY, Tseng YH, Chang CC, Wu CK, Lin JL, Tseng WY. CMR-verified diffuse myocardial fibrosis is associated with diastolic dysfunction in HFpEF. JACC Cardiovasc Imaging. 2014 Oct;7(10):991-7. doi: 10.1016/j.jcmg.2014.04.022. Epub 2014 Sep 17. PMID 25240451
• Wu CK, Lee JK, Hsu JC, Su MM, Wu YF, Lin TT, Lan CW, Hwang JJ, Lin LY. Myocardial adipose deposition and the development of heart failure with preserved ejection fraction. Eur J Heart Fail. 2020 Mar;22(3):445-454. doi: 10.1002/ejhf.1617. Epub 2019 Sep 11. PMID 31696627
• Solomon SD, McMurray JJV, Vaduganathan M, Claggett B, Jhund PS, Desai AS, Henderson AD, Lam CSP, Pitt B, Senni M, Shah SJ, Voors AA, Zannad F, Abidin IZ, Alcocer-Gamba MA, Atherton JJ, Bauersachs J, Chang-Sheng M, Chiang CE, Chioncel O, Chopra V, Comin-Colet J, Filippatos G, Fonseca C, Gajos G, Goland S, Goncalvesova E, Kang S, Katova T, Kosiborod MN, Latkovskis G, Lee AP, Linssen GCM, Llamas-Espe PMID 39225278
• 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. PMID 34449181
• 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. PMID 33264825

Идентификаторы

NCT: NCT07442448 · CGH-P114066 · 202511026MINE

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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