Randomized Trial to Determine the Efficacy and Safety of Finerenone on Morbidity and Mortality Among Heart Failure Patients With Left Ventricular Ejection Fraction Greater Than or Equal to 40% Hospitalized Due to an Episode of Acute Decompensated Heart Failure (REDEFINE-HF)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 5,200
- 试验地点
- 11
- 主要终点
- 1. Composite total of HF events and cardiovascular (CV) death. Total (first and subsequent) HF hospitalizations, urgent visits for worsening HF, and CV deaths with finerenone compared to placebo.
研究概览
简要总结
This is a Phase 3 randomized, double blind trial where Finerenone will be compared with placebo to determine the efficacy and safety of treatment in patients hospitalized with acute decompensated heart failure (HF) and mildly reduced or preserved left ventricular ejection fraction.
Since patients hospitalized for acute decompensated HF, including those with HFp/mrEF, are at high risk of subsequent adverse events (AEs), including hospital readmissions and urgent visits due to HF, as well as CV death,currently there is a substantial and unmet need for additional efficacious and safe treatment options.
Establishing that finerenone can provide an early reduction in the risk of HF events and CV death among patients with acute HFp/mrEF would significantly change clinical practice.
Patients will be screened based on the inclusion/exclusion criteria and will be randomly allocated(1:1) to receive one finerenone or matching placebo tablet orally each day.The dose will be adjusted based on the patient’s kidney function and serum/plasma potassium.
The outcome will be assessed based on the primary objective: whether Finerenone reduces total HF events and CV death compared with placebo in patients hospitalized with acute decompensated HFmrEF/HFpEF, secondary objective: by determining the effects of finerenone compared with placebo on clinical events and change in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and the safety objective: by assessing the occurrence of AEs with finerenone compared with placebo.
The analysis of the endpoints will be performed as per the Statistical Analysis Plan.
DCGI approval was obtained for the study on 3-Jan-2025.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Provide electronic or written informed consent, either personally or through a legally authorized representative.
- •Age ≥ 18 years.
- •Current hospitalization or recently discharged with the primary diagnosis of heart failure.
- •Heart failure signs and symptoms at the time of hospital admission.
- •Imaging evidence of mildly reduced or preserved left ventricular ejection fraction (EF) (40% or higher).
- •Elevated N-terminal pro B-type natriuretic peptide (NTproBNP) ≥ 1000 pg/mL or B-type natriuretic peptide (BNP) ≥ 250 pg/mL for patients without atrial fibrillation (AF); or elevated NTproBNP ≥ 2000 pg/mL or BNP ≥ 500 pg/mL for patients with AF.
- •Systolic blood pressure (BP) ≥ 100 mmHg and no symptoms of hypotension in the 6 hours prior to randomization; b.
- •No increase in intravenous diuretic dose for 6 hours prior to randomization; c.
- •No intravenous vasodilators, including nitrates, within the last 6 hours prior to randomization; d.
- •No intravenous inotropic drugs or mechanical circulatory support for 24 hours prior to randomization.
- •Treatment during the index hospitalization with at least 1 intravenous dose of a loop diuretic, e.g. furosemide, torsemide, bumetanide.
- •Women of childbearing potential1 can only be included in the study if a pregnancy test is negative at screening and if they agree to use adequate contraception which is consistent with local regulations regarding the methods for contraception for the duration of the study.
排除标准
- •Treatment with a mineralocorticoid receptor antagonist (MRA).
- •Documented prior history of sever hyperkalemia in the setting of MRA use.
- •Estimated glomerular filtration rate (eGFR) less than 25mL/min/1.73m2 or serum/plasma potassium more than 5.0mmol/L at screening.
- •Acute myocardial infarction, coronary revascularization, valve replacement/repair, or implantation of a cardiac resynchronization therapy device within 30 days.
- •Prior heart transplant or listed for heart transplant with expectation to receive a transplant during the course of this trial, or planned for palliative care for HF, or currently using or plan for mechanical circulatory support, e.g., left ventricular assist device, intra-aortic balloon pump, or patients on mechanical ventilation or patients with planned outpatient inotropic support.
- •Hemodynamically significant (severe) uncorrected primary cardiac valvular disease.
- •Cardiomyopathy due to known acute inflammatory heart, infiltrative diseases, accumulation diseases, muscular dystrophies, cardiomyopathy with reversible causes, known hypertrophic obstructive cardiomyopathy, complex congenital heart disease, or known pericardial constriction.
- •Probable alternative cause of participants heart failure symptoms.
- •Concomitant systemic therapy with potent cytochrome P450 isoenzyme 3A4 (CYP3A4) inhibitors or moderate CYP3A4 inducers, or potent CYP3A4 inducers.
- •Concomitant treatment with renin inhibitor, more than one angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blocker (ARB) or ARNI, or with a potassium-sparing diuretic.
- •Any other condition or therapy (e.g., cardiogenic shock, clinically overt severe hepatic insufficiency, Addison’s disease, or other severe condition.
- •Participation in another interventional clinical study or treatment with another investigational medicine or device within 30 days prior to randomization.
结局指标
主要结局
1. Composite total of HF events and cardiovascular (CV) death. Total (first and subsequent) HF hospitalizations, urgent visits for worsening HF, and CV deaths with finerenone compared to placebo.
时间窗: Ongoing, up to 30 months
2. Number of serious adverse events. Occurrence of serious adverse events (excluding efficacy endpoints) with finerenone compared to placebo.
时间窗: Ongoing, up to 30 months
3. Number of adverse events leading to discontinuation of study drug. Occurrence of serious adverse events leading to study drug discontinuation with finerenone compared to placebo.
时间窗: Ongoing, up to 30 months
次要结局
- Time to death from any cause with finerenone compared to placebo.(Ongoing, up to 30 months)
- Time to first occurrence of the composite of CV death or HF event.(Ongoing, up to 30 months)
- Total HF events.(Ongoing, up to 30 months)
- Change from baseline in the Total Symptom Score on the Kansas City Cardiomyopathy Questionnaire (KCCQ-TSS) at Month 6.(6 months)
- Time to CV death with finerenone compared to placebo.(Ongoing, up to 30 months)
研究者
Dr Vijay Kumar Chopra
Max Super Speciality Hospital