A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Efficacy and Safety of Finerenone on Morbidity and Mortality in Participants With Heart Failure (NYHA II-IV) and Left Ventricular Ejection Fraction ≥ 40% (LVEF ≥ 40%)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 6,016
- 试验地点
- 661
- 主要终点
- Occurrence of the Composite Endpoint of Cardiovascular Death and Total (First and Recurrent) Heart Failure Events
研究概览
简要总结
The purpose of this study is to evaluate the effect of finerenone compared to placebo (a tablet without active substance) in the reduction of cardiovascular death (generally meaning death due to disease of the heart or blood vessels) and total Heart Failure (HF) events, including HF hospitalization and urgent visits for HF(generally meaning a hospital stay or urgent presentation to a healthcare unit due to worsening symptoms of heart failure) in patients suffering from HF with an ejection fraction greater than or equal to 40%. Researchers will also collect information on how much the heart disease has impact on patient's lives, change of kidney function, and how well finerenone treatment is tolerated. The study plans to enroll 6000 male and female patients of the age of 40 years and above suffering from heart failure with ejection fraction greater than or equal to 40%. Participants will take the study product as oral tablet with a dose between 0 (Placebo) 40 mg once daily. Study duration will be up to 43 months.
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
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant (male or female) must be aged 40 years and older.
- •Diagnosis of heart failure with New York Heart Association(NYHA) class II-IV, ambulatory or hospitalized primarily for heart failure.
- •On diuretic treatment for at least 30 days prior to randomization.
- •Documented left ventricular ejection fraction (LVEF) of ≥40% measured by any modality within the last 12 months.
- •Structural heart abnormalities based on any local imaging measurement within the last 12 months, defined by at least one of the following findings: left atrial diameter (LAD) ≥3.8cm, left atrial area (LAA) ≥20cm2, left atrial volume index (LAVI) >30 mL/m2, left ventricular mass index (LVMI) ≥115 g/m2 (♂)/ 95 g/m2 (♀), septal thickness or posterior wall thickness ≥1.1 cm
- •n-terminal prohormone B-type natriuretic peptide (NT-proBNP) ≥300 pg/mL (BNP ≥100 pg/mL) in sinus rhythm and patient does not have an ongoing diagnosis of paroxysmal atrial fibrillation or NT-proBNP ≥900 pg/mL (BNP ≥300 pg/mL) in atrial fibrillation (or if atrial fibrillation status is unknown or if patient has an ongoing diagnosis of paroxysmal atrial fibrillation) for participants obtained at the following time:
- •Within 90 days prior to randomization if patient had been hospitalized for heart failure (HF) requiring initiation or change in HF therapy or if patient had an urgent visit for HF requiring intravenous (IV) diuretic therapy, both within 90 days prior to randomization OR
- •Within 30 days prior to randomization if patient has not been hospitalized for HF nor had an urgent HF visit within the past 90 days.
- •Women of childbearing potential can only be included in the study if a pregnancy test is negative at screening and baseline and if they agree to use adequate contraception which is consistent with local regulations regarding the methods for contraception for those participating in clinical trials.
排除标准
- •Estimated glomerular filtration rate (eGFR) <25 mL/min/1.73 m² at either screening or randomization visit.
- •Serum/plasma potassium >5.0 mmol/L at either screening or randomization visit.
- •Acute inflammatory heart disease, e.g. acute myocarditis, within 90 days prior to randomization
- •Myocardial infarction or any event which could have reduced the ejection fraction within 90 days prior to randomization
- •Coronary artery bypass graft surgery in the 90 days prior to randomization
- •Percutaneous coronary intervention in the 30 days prior to randomization
- •Stroke or transient ischemic cerebral attack within 90 days prior to randomization
- •Probable alternative cause of participants' HF symptoms that in the opinion of the investigator primarily accounts for patient's dyspnea such as significant pulmonary disease, anemia or obesity. Specifically, patients with the below are excluded: Severe pulmonary disease requiring home oxygen, or chronic oral steroid therapy, History of primary pulmonary arterial hypertension, Hemoglobin <10 g/dl, Valvular heart disease considered by the investigator to be clinically significant, Body Mass Index (BMI) >50 kg/m2 at screening
- •Systolic blood pressure(SBP) ≥160 mmHg if not on treatment with ≥3 blood pressure lowering medications or ≥180 mmHg irrespective of treatments, on 2 consecutive measurements at least 2-minute apart, at screening or at 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.
研究组 & 干预措施
Arm 1_BAY94-8862
Adult patients receive BAY94-8862
干预措施: Finerenone (BAY94-8862) (Drug)
Arm 2_Placebo
Adult patients receive placebo
干预措施: Placebo (Other)
结局指标
主要结局
Occurrence of the Composite Endpoint of Cardiovascular Death and Total (First and Recurrent) Heart Failure Events
时间窗: From randomization up until the end of study, with an average study duration of 32 months
Number of participants with composite endpoint events of cardiovascular death and total (first and recurrent) heart failure (HF) events (hospitalization for heart failure or urgent HF visit) in HF patients.
次要结局
- Occurrence of Total (First and Recurrent) Heart Failure Events(From randomization up until the end of study, with an average study duration of 32 months)
- Change From Baseline in Total Symptom Score (TSS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ)(From baseline to Month 6, 9 and 12)
- Proportion of Participants Who Showed Improvement in NHYA Class(from baseline to Month 12)
- First Occurrence of Renal Composite Events(From randomization up to end of study visit, with an average study duration of 32 months)
- Occurence of All-cause Mortality (Full Analysis Set)(From randomization until end of study, with an average of 32 months)