Finerenone and Cardiac Remodeling: A Randomized, Double- Blind, Placebo-Controlled Study to Evaluate The Effects of Finerenone on Ventricular Remodeling
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 156
- 试验地点
- 3
- 主要终点
- Left ventricular mass indexed to baseline body surface area (LVMi)
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
- •Estimated glomerular filtration rate (eGFR) ≥25 and <75 mL/min/1.73 m^2;
- •Urine albumin-creatinine ratio (UACR) >3.39 mg/mmol and <565 mg/mmol;
- •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);
- •IVS ≥1.4 cm;
- •PW ≥1.4 cm;
- •LVMi ≥125 g⁄m^2 for males and ≥105 g⁄m^2 for females (by echocardiography);
- •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.
- •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.
排除标准
- •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 exclusion criteria;
- •Requirement of any intravenous (IV) vasodilating drug (e.g. nitrates, nitroprusside), any IV natriuretic peptide (e.g. nesiritide, carperitide), any IV positive inotropic agents, or mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device) ≤24 hours prior to randomization;
- •Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors (e.g. itraconazole, ritonavir, indinavir, cobicistat, clarithromycin) or moderate or potent CYP3A4 inducers, that cannot be discontinued 7 days prior to randomization and for the duration of the treatment period;
- •History of cardiac device implant (e.g. implantable cardioverter defibrillator/cardiac resynchronization therapy/pacemaker) or planned device implant ≤90 days after screening;
- •Hospitalized for heart failure (HF) requiring initiation or change in HF therapy or an urgent visit for HF requiring IV diuretic therapy, either ≤45 days prior to screening;
- •LVEF <40% per the most current echocardiogram or MRI;
- •Symptomatic bradycardia or second- or third-degree heart block without a pacemaker;
- •History of peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, viral myocarditis, right HF in the absence of left-sided structural disease, pericardial constriction, hypertrophic cardiomyopathy, or infiltrative cardiomyopathy including amyloidosis;
- •Myocardial infarction ≤45 days of screening;
- •Planned or previous cardiac surgery or major non-cardiac surgery ≤45 days of screening;
- •Planned or previous percutaneous coronary intervention ≤45 days of screening;
- •Stroke or transient ischemic stroke ≤90 days before randomization;
- •Severe valvular heart disease;
- •Addison's disease;
- •Individuals who are heart or kidney transplant recipients or who are (or are expected to be) listed for heart transplant, kidney dialysis or a kidney transplant ≤12 months of screening;
- •Any other known condition or therapy which would make the individual unsuitable for this trial (e.g. hepatic insufficiency, liver biomarkers >3X upper limit of normal, chronic pulmonary disease, life threatening arrhythmia, uncontrolled arrhythmia) or not allow participation for the full planned trial duration (e.g. active malignancy ≤24 months of screening or condition limiting life expectancy to <12 months);
- •Allergy to finerenone (or its excipients);
- •Allergy to gadolinium;
- •Participation in an investigational study ≤15 days prior to screening, or during study.
研究组 & 干预措施
Finerenone
Active treatment group
干预措施: Finerenone (Drug)
Placebo
Control treatment group
干预措施: Placebo (Drug)
结局指标
主要结局
Left ventricular mass indexed to baseline body surface area (LVMi)
时间窗: 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.
次要结局
- 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)
研究者
Subodh Verma
Professor of Surgery and Pharmacology & Toxicology
Canadian Medical and Surgical Knowledge Translation Research Group