Heart Failure
Conditions
Keywords
Heart failure with mildly reduced ejection fraction, Heart failure with preserved ejection fraction, Myocardial fibrosis, Imaging
Brief summary
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.
Detailed description
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.
Interventions
DRUGOral finerenone
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.
DRUGPlacebo
Standard heart failure therapy plus matching placebo
Sponsors
China National Center for Cardiovascular Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18 to 80 years (inclusive), any gender. 2. Symptomatic heart failure (NYHA class II-IV). 3. Emergency department visit or hospitalization for HF within the past 3 months, or escalation of intravenous or oral diuretic therapy for worsening HF within the past 3 months. 4. LVEF ≥40% measured by echocardiography or CMR within the past 30 days prior to screening. 5. NT-proBNP ≥300 pg/mL for patients in sinus rhythm; NT-proBNP ≥900 pg/mL for patients with atrial fibrillation. 6. Presence of myocardial fibrosis, defined as ECV ≥27% measured by CMR at baseline. 7. Capable of providing voluntary written informed consent.
Exclusion criteria
* 1\. eGFR \<25 mL/min/1.73 m² at screening or enrollment. 2. Serum potassium concentration ≥5.0 mmol/L at screening or enrollment. 3. Prior confirmed diagnosis of HFrEF. 4. Acute inflammatory heart disease (e.g., acute myocarditis). 5. Acute myocardial infarction or other event likely to have reduced LVEF within 30 days prior to randomization. 6\. Coronary artery bypass grafting within 30 days prior to randomization. 7. Percutaneous coronary intervention within 30 days prior to randomization. 8. History of stroke or transient ischemic attack (TIA) within 90 days prior to randomization. 9\. Conditions where the investigator considers the primary cause of dyspnea (and thus heart failure symptoms) to be severe pulmonary disease, anemia, or obesity. Specific exclusions include: severe pulmonary disease requiring home oxygen therapy or long-term oral steroids; history of primary pulmonary hypertension; hemoglobin \<100 g/L; severe valvular heart disease; BMI ≥50 kg/m². 10\. Systolic blood pressure (SBP) \>160 mmHg despite combination therapy with 3 antihypertensive drugs, OR SBP \>180 mmHg on any treatment measured on (two consecutive occasions at least 2 minutes apart). 11\. Severe malignant ventricular arrhythmia or atrial fibrillation with resting ventricular rate \>100 bpm. 12\. Symptomatic hypotension with mean SBP \<90 mmHg. 13. Any HF condition requiring surgical intervention (e.g., severe aortic stenosis or mitral regurgitation). 14\. History of peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, viral myocarditis, primary right ventricular cardiomyopathy, constrictive pericarditis, hereditary hypertrophic cardiomyopathy, or infiltrative cardiomyopathy (including amyloidosis). 15\. Contraindications to CMR (e.g., magnetic metal implants, claustrophobia, contrast allergy). 16\. History of hyperkalemia or acute renal failure during prior MRA therapy. 17. Known allergy or severe adverse reaction to finerenone. 18. History of severe hepatic impairment (Child-Pugh C). 19. Requirement for any intravenous inotropic drugs or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) within 24 hours prior to randomization. 20\. Current or prior use (within 4 weeks before screening) of any MRA (e.g., spironolactone, eplerenone, canrenone, esaxerenone). 21\. Use of renin inhibitors or potassium-sparing diuretics prior to randomization that cannot be discontinued. 22\. Severe comorbidities (e.g., malignancy, lymphoma, cirrhosis, HIV-positive) with life expectancy \<2 years. 23\. Pregnancy, lactation, or planning pregnancy. Women of childbearing potential must have a negative serum pregnancy test pre-treatment, agree to serum/urine pregnancy tests at study visits (Months 3 and 6), and commit to using highly effective contraception during the study and for 3 months after. Male participants with female partners of childbearing potential must also agree to use highly effective contraception during the study and for 3 months after. 24\. Participation in another clinical trial within 3 months prior to this study. 25\. Any condition, in the investigator's judgment, that would preclude safe study participation or protocol compliance.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in CMR-measured extracellular volume (ECV) from baseline to Month 6 (∆ECV = ECV[post-treatment] - ECV[baseline]) | 6 months |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline to 6 months in CMR-measured parameter: left ventricular end-diastolic volume index | 6 months |
| Change from baseline to 6 months in CMR-measured parameter: left ventricular end-systolic volume index | 6 months |
| Change from baseline to 6 months in CMR-measured parameter: left ventricular mass index | 6 months |
| Change from baseline to 6 months in CMR-measured parameter: left ventricular ejection fraction | 6 months |
| Change from baseline to 6 months in CMR-measured parameter: left atrial volume index | 6 months |
| Change from baseline to 6 months in CMR-measured parameter: left ventricular myocardial strain | 6 months |
| Change from baseline to 6 months in echocardiography-measured parameter: tricuspid regurgitation velocity | 6 months |
| Change from baseline to 6 months in echocardiography-measured parameter: E/e' ratio | 6 months |
| Change in CMR native T1 mapping from baseline to 6 months | 6 months |
| Change in LGE mass from baseline to 6 months | 6 months |
| Change in LGE percentage of left ventricular mass from baseline to 6 months | 6 months |
| Change in Pulmonary artery pressure by echocardiography from baseline to 6 months | 6 months |
| Change from baseline to 6 months in levels of NT-proBNP | 6 months |
| Change from baseline to 6 months in levels of total PINP | 6 months |
| Change from baseline to 6 months in levels of PIIINP | 6 months |
| Change from baseline to 6 months in levels of β-crosslaps | 6 months |
| Change from baseline to 6 months in levels of sST2 | 6 months |
Countries
China
Contacts
CONTACTXiao Wang, MD
CONTACTYingying Guo, MD
PRINCIPAL_INVESTIGATORKe fei Dou, MD
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
PRINCIPAL_INVESTIGATORXiao Wang
Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College
Outcome results
None listed