Finerenone and Cardiac Remodeling: A Randomized, Double- Blind, Placebo-Controlled Study to Evaluate The Effects of Finerenone on Ventricular Remodeling
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Subodh Verma
- Enrollment
- 156
- Locations
- 3
- Primary Endpoint
- Left ventricular mass indexed to baseline body surface area (LVMi)
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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:
- •Interventricular septal (IVS) thickness by echocardiography: Female ≥1.2 cm or Male ≥1.3 cm
- •Posterior wall (PW) thickness by echocardiography: Female ≥1.2 cm or Male ≥1.3 cm
- •Left ventricular mass indexed to baseline body surface area (LVMi) by echocardiography: Female \>95 g⁄m\^2 or Male \>115 g⁄m\^2
- •LVMi (with papillary muscles included in the LV blood pool) by cMRI: Female \>59 g⁄m\^2 or Male \>75 g⁄m\^2
- •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:
- •History of heart failure with preserved ejection fraction (left ventricular ejection fraction \[LVEF\] ≥50%);
- •Type 2 diabetes mellitus;
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;
Arms & Interventions
Finerenone
Active treatment group
Intervention: Finerenone (Drug)
Placebo
Control treatment group
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Left ventricular mass indexed to baseline body surface area (LVMi)
Time Frame: 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 Outcomes
- Right Ventricular Ejection Fraction (RVEF)(12 months)
- Left Ventricular Ejection Fraction (LVEF)(12 months)
- Left Atrial Volume indexed to baseline body surface area (LAVi)(12 months)
- Left Ventricular End-Diastolic Volume indexed to baseline body surface area (LVEDVi)(12 months)
- Left Ventricular End-Systolic Volume indexed to baseline body surface area (LVESVi)(12 months)
- Right Ventricular End-Diastolic Volume indexed to baseline body surface area (RVEDVi)(12 months)
- Right Ventricular End-Systolic Volume indexed to baseline body surface area (RVESVi)(12 months)
Investigators
Subodh Verma
Professor of Surgery and Pharmacology & Toxicology
Canadian Medical and Surgical Knowledge Translation Research Group