Heart Failure
Conditions
Keywords
Finerenone, Left Ventricle Remodeling, Double-blind, Randomized, Heart Failure, Multicentre, Cardiorenal
Brief summary
The goal of this clinical trial is to learn if the drug finerenone (Karendia) can improve heart function in participants who are at risk for heart and kidney disease. The main question it aims to answer is whether adding finerenone to standard-of-care heart failure medical therapies will beneficially alter the heart structure and function of people who have risk factors for heart and kidney complications and whose left side of the heart is enlarged. The researchers will compare finerenone to a placebo (a look-alike substance that contains no drug) to see if finerenone improves heart structure and function. Participants will: * take a finerenone or a placebo tablet once a day for 12 months * have a cardiac magnetic resonance imaging (cMRI; a safe, non-invasive scan to measure heart mass, stiffness and function) test at the beginning of the study and 12 months later * visit the clinic after one, three, six and twelve months to assess overall health and/or perform blood or urine tests
Detailed description
Finerenone is a potent and selective oral non-steroidal mineralocorticoid receptor antagonist that has demonstrated marked cardiovascular benefits in people living with diabetic kidney disease, heart failure with mildly reduced ejection fraction, and heart failure with preserved ejection fraction. However, the mechanistic basis of these broad cardiovascular benefits remains unclear. The FINE-MECH CardioLink-11 trial is a multicentre, prospective, randomized, double-blind trial of finerenone vs placebo in addition to standard-of-care in adults with evidence of left ventricular hypertrophy and cardiorenal risk factors. A total of 156 individuals who provide written informed consent and meet all the inclusion criteria (and none of the exclusion criteria) will be assigned (1:1) to receive either finerenone or placebo QD for 12 months. There will be 6-7 clinic visits. Outcome assessors will be blinded to the investigational product allocation and the time point at which each assessment was completed.
Interventions
DRUGFinerenone
Participants will be allocated a starting dose of 10 or 20 mg of finerenone (dependent on kidney function) once daily, in addition to standard-of-care. Participants may be up-titrated or down-titrated based on potassium levels or estimated glomerular filtration rate with a minimum dose of 10 mg and maximum dose of 40 mg finerenone
DRUGPlacebo
Participants will be allocated a starting dose of 10 or 20 mg of placebo (dependent on kidney function) once daily, in addition to standard-of-care. Participants may be up-titrated or down-titrated based on potassium levels or estimated glomerular filtration rate with a minimum dose of 10 mg and maximum dose of 40 mg placebo
Sponsors
Bayer
Subodh Verma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Prospective, double-blinded, randomized (1:1), placebo-controlled trial of finerenone vs placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Individuals ≥18 years of age who are willing and able to provide signed informed consent * Evidence of left ventricular (LV) hypertrophy ≤12 months prior to or at screening showing at least one (≥1) of the following: 1. Interventricular septal (IVS) thickness by echocardiography: Female ≥1.2 cm or Male ≥1.3 cm 2. Posterior wall (PW) thickness by echocardiography: Female ≥1.2 cm or Male ≥1.3 cm 3. Left ventricular mass indexed to baseline body surface area (LVMi) by echocardiography: Female \>95 g⁄m\^2 or Male \>115 g⁄m\^2 4. LVMi (with papillary muscles included in the LV blood pool) by cMRI: Female \>59 g⁄m\^2 or Male \>75 g⁄m\^2 5. LVMi (if the papillary muscles are included in the LVM) by cMRI: Female \>68 g⁄m\^2 or Male \>85 g⁄m\^2 * The presence of at least one (≥1) of the following risk factors: 1. History of heart failure with preserved ejection fraction (left ventricular ejection fraction \[LVEF\] ≥50%); 2. Type 2 diabetes mellitus; 3. Estimated glomerular filtration rate (eGFR) ≥25 and \<75 mL/min/1.73 m\^2; 4. Urine albumin-creatinine ratio (UACR) \>3.39 mg/mmol and \<565 mg/mmol; 5. Left atrial volume indexed to baseline body surface area (LAVi) \>40 mL/m\^2 (by echocardiography and as measured by either the biplane area-length method or Simpson's biplane method); 6. IVS ≥1.4 cm; 7. PW ≥1.4 cm; 8. LVMi ≥125 g⁄m\^2 for males and ≥105 g⁄m\^2 for females (by echocardiography); 9. N-terminal pro-B-type natriuretic peptide (NT-proBNP; within past 6 months) ≥150 pg/mL if in sinus rhythm or ≥450 pg/mL if atrial fibrillation is present. 10. Females who are of childbearing age can only be included if I. they are postmenopausal (i.e. no menstruation for at least one \[≥1\] year) or have had a surgical procedure ≥6 months at screening that prevents them from becoming pregnant; or II. the result of their pregnancy test at the baseline visit is negative, and they agree to use medically acceptable contraception methods to avoid pregnancy for the duration of the trial and for 1 month after taking the last dose of the assigned investigational product.
Exclusion criteria
* Females who are planning to become pregnant, are breastfeeding or are planning to breastfeed; * Males who are planning to either father a child or donate sperm for the duration of the trial and for 1 month after taking the last dose of the assigned IP; * Serum potassium level ≥5 mmol/L at the time of screening; * eGFR \<25 mL/min/1.73 m\^2 at the time of screening or on kidney replacement therapy; * UACR ≥565 mg/mmol at the time of screening; * Seated systolic blood pressure \<110 mmHg at the time of screening; * History of pulmonary arterial hypertension; * Type 1 diabetes mellitus; * Body mass index ≥40 kg/m\^2; * Contraindication or inability to undergo MRI; * Known persistent hypoalbuminemia (≤30 g/L on \>1 measurement within last 6 months); * Currently on a mineralocorticoid receptor antagonist (MRA) or in the opinion of the investigator, an MRA is either clinically indicated or contraindicated (e.g. history of marked hyperkalemia, marked hemodynamic stress, intolerance to MRAs) - individuals who previously experienced gynecomastia with spironolactone may be eligible if they meet all the inclusion criteria and none of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular mass indexed to baseline body surface area (LVMi) | 12 months | Change in LVMi (g/m\^2), measured by cardiac magnetic resonance imaging (cMRI) from baseline to 12 months of treatment with finerenone compared to placebo. cMRI evaluations will be made from standard 2D views with and without gadolinium as a contrast agent. All acquired sequences will adhere to the current clinical standard of care. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular End-Diastolic Volume indexed to baseline body surface area (LVEDVi) | 12 months | Change in LVEDVi, measured by cMRI and indexed to baseline body surface area, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Left Ventricular End-Systolic Volume indexed to baseline body surface area (LVESVi) | 12 months | Change in LVESVi, measured by cMRI and indexed to baseline body surface area, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Right Ventricular Ejection Fraction (RVEF) | 12 months | Change in RVEF, measured by cMRI, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Left Ventricular Ejection Fraction (LVEF) | 12 months | Change in LVEF, measured by cMRI, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Right Ventricular End-Systolic Volume indexed to baseline body surface area (RVESVi) | 12 months | Change in RVESVi, measured by cMRI and indexed to baseline body surface area, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Left Atrial Volume indexed to baseline body surface area (LAVi) | 12 months | Change in LAVi, measured by cMRI and indexed to baseline body surface area, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Right Ventricular End-Diastolic Volume indexed to baseline body surface area (RVEDVi) | 12 months | Change in RVEDVi, measured by cMRI and indexed to baseline body surface area, from baseline to 12 months of treatment with finerenone compared to placebo. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Focal and Diffuse Fibrosis | 12 months | Effect on focal fibrosis (assessed by late gadolinium enhancement and diffuse fibrosis (assessed by extracellular volume using T1 mapping) measured by cMRI, from baseline to 12 months of treatment with finerenone compared to placebo. |
| N-terminal pro-B-type natriuretic peptide (NT-proBNP) Levels | 12 months | Change in NT-proBNP concentration from baseline to 12 months of treatment with finerenone compared to placebo. |
| Myocardial Strain Parameters - left ventricular global longitudinal strain | 12 months | Effect on left ventricular global longitudinal strain, assessed by speckle tracking echocardiography and/or feature-tracking cMRI, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Myocardial Strain Parameters - global circumferential strain | 12 months | Effect on global circumferential strain, assessed by speckle tracking echocardiography and/or feature-tracking cMRI, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Myocardial Strain Parameters - global radial strain | 12 months | Effect on global radial strain, assessed by speckle tracking echocardiography and/or feature-tracking cMRI, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Myocardial Strain Parameters - diastolic strain rate | 12 months | Effect on diastolic strain rate, assessed by speckle tracking echocardiography and/or feature-tracking cMRI, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Myocardial Strain Parameters - right ventricular free wall strain | 12 months | Effect on right ventricular free wall strain, assessed by speckle tracking echocardiography and/or feature-tracking cMRI, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Myocardial Strain Parameters - left atrial strain | 12 months | Effect on left atrial strain, assessed by speckle tracking echocardiography and/or feature-tracking cMRI, from baseline to 12 months of treatment with finerenone compared to placebo. |
| Myocardial Strain Parameters - right atrial strain | 12 months | Effect on right atrial strain, assessed by speckle tracking echocardiography and/or feature-tracking cMRI, from baseline to 12 months of treatment with finerenone compared to placebo. |
Countries
Canada
Contacts
Primary ContactSubodh Verma, MD, PhD
Outcome results
None listed