FINE-FOCUS study is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effect of Finerenone versus placebo on myocardial fibrosis and cardiac structure/function as assessed by cardiac magnetic resonance (CMR) in symptomatic heart failure patients with a left ventricular ejection fraction (LVEF) ≥40%. A sub-study will include 18F-FAPI-PET/CT imaging to evaluate the effect of finerenone on myocardial fibrosis.
Heart failure (HF) with mildly reduced ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) are common and associated with high morbidity and mortality. A diverse range of pathophysiological mechanisms is involved in HFmrEF/HFpEF, and this heterogeneity has made it challenging to demonstrate a reduction in mortality in trials to date. Preclinical studies have established myocardial fibrosis as a key pathophysiological driver of heart failure. In patients with HFmrEF/HFpEF, myocardial fibrosis, assessed by cardiovascular magnetic resonance, is associated with mortality and heart failure hospitalization. Finerenone is a non-steroidal mineralocorticoid receptor antagonist and exhibits more potent anti-inflammatory and antifibrotic effects than steroidal mineralocorticoid receptor antagonists in preclinical models. Specifically targeting the extracellular matrix may represent a novel therapeutic approach for heart failure, the FINE-FOCUS study(A Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effect of Finerenone on Myocardial Fibrosis and Cardiac Structure and Function in Heart Failure Patients with Mildly Reduced or Preserved Ejection Fraction) was designed to test whether finerenone induces regression of myocardial fibrosis in patients with HFmrEF/HFpEF and evidence of myocardial fibrosis. PET-CT substudy: A subset of eligible patients will be enrolled into a sub-study to evaluate the effect of finerenone on myocardial fibrosis assessed by 18F-FAPI-PET/CT.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Standard heart failure therapy plus oral finerenone eGFR ≤60 mL/min/1.73 m²: Start 10 mg once daily, target 20 mg once daily. eGFR \>60 mL/min/1.73 m²: Start 20 mg once daily, target 40 mg once daily. Dose adjustments are mandated based on serum potassium levels and eGFR changes.
Standard heart failure therapy plus matching placebo
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Beijing, China
Change in CMR-measured extracellular volume (ECV) from baseline to Month 6 (∆ECV = ECV[post-treatment] - ECV[baseline])
Time frame: 6 months
Change from baseline to 6 months in CMR-measured parameter: left ventricular end-diastolic volume index
Time frame: 6 months
Change from baseline to 6 months in CMR-measured parameter: left ventricular end-systolic volume index
Time frame: 6 months
Change from baseline to 6 months in CMR-measured parameter: left ventricular mass index
Time frame: 6 months
Change from baseline to 6 months in CMR-measured parameter: left ventricular ejection fraction
Time frame: 6 months
Change from baseline to 6 months in CMR-measured parameter: left atrial volume index
Time frame: 6 months
Change from baseline to 6 months in CMR-measured parameter: left ventricular myocardial strain
Time frame: 6 months
Change from baseline to 6 months in echocardiography-measured parameter: tricuspid regurgitation velocity
Time frame: 6 months
Change from baseline to 6 months in echocardiography-measured parameter: E/e' ratio
Time frame: 6 months
Change in CMR native T1 mapping from baseline to 6 months
Time frame: 6 months
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Enrollment
104
Change in LGE mass from baseline to 6 months
Time frame: 6 months
Change in LGE percentage of left ventricular mass from baseline to 6 months
Time frame: 6 months
Change in Pulmonary artery pressure by echocardiography from baseline to 6 months
Time frame: 6 months
Change from baseline to 6 months in levels of NT-proBNP
Time frame: 6 months
Change from baseline to 6 months in levels of total PINP
Time frame: 6 months
Change from baseline to 6 months in levels of PIIINP
Time frame: 6 months
Change from baseline to 6 months in levels of β-crosslaps
Time frame: 6 months
Change from baseline to 6 months in levels of sST2
Time frame: 6 months