Project Portugal 2030

Summary

FIBROFINE as an investigator initiated trial aims to study in detail the impact of finerenone in a population different from the one finerenone is already approved for: patients with high cardiovascular risk, irrespective of type 2 diabetes. The effect will be studied by myocardial fibrosis quantification by CMR - ECV and secondary endpoints. Specifically, FIBROFINE's primary objective is to assess the effect of finerenone (9 months of therapy) vs. placebo in myocardial fibrosis evaluated by ECV at CMR. The primary outcome will be the 9-months change from baseline in CMR-ECV between finerenone and placebo. Secondary objectives are to assess the 9-month change from baseline in: 1) Circulating levels of MF markers (Table 1); 2) Cardiac structure and function as assessed by transthoracic echocardiography; 3) Cardiac structure and function as assessed by CMR; 4) Seated systolic and diastolic blood pressure (SBP/DBP); 5) Estimated glomerular filtration rate (eGFR); 6) Microalbuminuria (spot urine); 7) Urinary sodium/natriuresis (spot urine); 8) Serum potassium (K+); 9) Arterial stiffness assessed by pulse wave velocity; 10) Endothelial function by peripheral arterial tonometry; 11) Bioelectrical impedance; 12) Circulating biomarkers of myocardial remodelling (cardiomyocyte injury and inflammation) including N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP), high sensitivity troponin I, and high-sensitivity C-reactive protein (hsCRP). In addition, we will assess the impact of finerenone vs. placebo on: 15) the incidence of de novo atrial fibrillation; 16) New use of loop diuretics; 17) Heart failure hospitalizations, myocardial infarction, and stroke; 18) Mortality. Safety outcome measures: 1) Severe hyperkalemia defined as a serum potassium >6.0 mmol/L; 2) Worsening renal function defined as an eGFR drop >50% from baseline; 3) Symptomatic hypotension defined as a SBP <90 mmHg with symptoms. Exploratory objectives: 1) To correlate the circulating MF markers with the MF burden determined by CMR (ECV); 2) To correlate the MF burden determined by CMR with echocardiographic left ventricular global longitudinal strain and other measures of cardiac structure and function; 3) To correlate the circulating markers of MF with echocardiographic left ventricular global strain and other measures of cardiac structure and function. In addition, the effect of finerenone (9 months of therapy) vs. placebo in CMR-ECV in patients with CMR-ECV <25% at baseline (i.e., fibrosis -) will also be evaluated. All above outcome measures will also be assessed in the exploratory trial. Patient’s characteristics will be compared between the main trial and the exploratory trial.