Open-label, Single-arm, Study Assessing the Efficacy and Safety of Ivabradine (Corlanor) in African-American/Black Subjects With Heart Failure and Left Ventricular Systolic Dysfunction
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change From Baseline in Heart Rate (HR) at Day 57
研究概览
简要总结
This study is a prospective, open-label, single-arm intervention study in African-American/Black subjects with heart failure and reduced ejection fraction (HFrEF).
There will be a 7-day screening period, a 57-day open-label treatment period, and a safety follow-up at day 87 or 30 days after the last administration of the investigational product.
详细描述
The goal of this study is to determine the impact of adding ivabradine therapy to the standard of care (SOC) in African-American/Black subjects with Heart Failure (HF) and reduced ejection fraction (HFrEF) on changes in heart rate (HR) from baseline (SOC alone). Changes in HR from baseline will be correlated with the changes from baseline in activity level of the subjects, as measured by both a standard 6-minute walk distance and an accelerometer device.
The primary hypothesis is that ivabradine effectively reduces HR between baseline and day 57 in African-American/Black subjects. Because mean reductions of approximately 5 beat per minute (bpm) have been observed in the overall placebo-treated subjects in the SHIFT study as well as in the placebo-treated subjects of the subgroup analysis of non-African-American/Black subjects enrolled in the SHIFT study, we will test whether the mean reduction with ivabradine exceeds 5 bpm, and estimate the degree to which the mean reduction with ivabradine exceeds 5 bpm.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has provided informed consent/assent prior to initiation of any study specific activities/ procedures
- •Male or female subject ≥ 18 years of age, describing self as African American/Black
- •Must have a diagnosis of heart failure (HF) confirmed by medical records, be in stable condition, and treated with stable optimal pharmacological therapy as per their personal physician's care.
- •Left ventricular ejection fraction (LVEF) ≤ 35% confirmed by investigator
- •New York Heart Association (NYHA) class II to IV assessed at the time of screening
- •Electrocardiogram (ECG) documentation at the time of screening of sinus rhythm with resting heart rate (HR) ≥ 70 bpm by local ECG reading
- •Must be able to complete a 6-minute walk test (6MWT) and wear an accelerometer
排除标准
- •Recent myocardial infarction (≤ 2 months) or stroke (≤ 1 month) prior to enrollment
- •If the subject received within 3 months before or is scheduled to receive within 42 days after enrollment any of the following: revascularization, ventricular assist device, continuous or intermittent inotropic therapy, hospice care, major organ transplant, or is receiving renal replacement therapy by dialysis
- •If the subject received implantation of a cardioverter defibrillator or cardiac resynchronization therapy within 42 days before or is scheduled to receive implantation of a cardioverter defibrillator or cardiac resynchronization therapy within 42 days after enrollment
- •Severe primary valve disease or scheduled for surgery for valvular heart disease
- •Pacemaker with atrial or ventricular pacing (except bi-ventricular pacing) >40% of the time, or with a stimulation threshold at the atrial or ventricular level ≥ 60 bpm
- •Permanent atrial fibrillation or flutter
- •Sick sinus syndrome, sinoatrial block, or second and third degree atrio-ventricular block
- •History of symptomatic or sustained (≥ 30 sec) ventricular arrhythmia unless a cardioverter defibrillator was implanted
- •History of congenital QT syndrome
- •Any cardioverter defibrillator shock experienced within 1 month of enrollment
- •Hypertrophic obstructive cardiomyopathy, active myocarditis or constrictive pericarditis, or clinically significant congenital heart disease
- •Chronic antiarrhythmic therapy (except digitalis)
- •Scheduled outpatient intravenous (IV) infusions for HF (eg, inotropes,vasodilators [eg, nesiritide], diuretics) or routinely scheduled ultrafiltration
- •Evidence of digitalis intoxication within 7 days prior to screening
- •Systolic blood pressure > 180 mm Hg or < 90 mm Hg, or diastolic blood pressure > 110 mm Hg or < 50 mm Hg at any time during the screening phase
- •Known untreated hypothyroidism or hyperthyroidism, adrenal insufficiency, active vasculitis due to collagen vascular disease
- •Have known acute or serious co-morbid condition (e.g, major infection or hematologic, renal, hepatic, metabolic, gastrointestinal or endocrine dysfunction) that may interfere with the study, or severe concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 1 year or malignancy within 5 years prior to enrollment with the following exceptions: localized basal or squamous cell carcinoma of the skin or cervical intraepithelial neoplasia
- •Subjects taking QT prolonging medicinal products for cardiovascular (e.g, but not limited to, quinidine, disopyramide, bepridil, sotalol, ibutilide, amiodarone) or non-cardiovascular disease (e.g, but not limited to, pimozide, ziprasidone, sertindole, mefloquine, halofantrine, pentamidine, cisapride, IV erythromycin).
- •Subjects exposed to a strong CYP3A4 inhibitor (examples of strong CYP3A4 inhibitors include; azole antifungals [eg, itraconazole], macrolide antibiotics [e.g, clarithromycin, telithromycin], human immunodeficiency virus (HIV) protease inhibitors, [eg, nelfinavir], and nefazodone]) within 14 days prior to enrollment, or to a strong CYP3A4 inducer (examples of CYP3A4 inducers include; St. John's wort, rifampicin, barbiturates, and phenytoin) within 28 days prior to enrollment
- •Subjects who received diltiazem or verapamil within 48 hours prior to enrollment.
- •Previously received ivabradine prior to participation in this study
- •Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
- •Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 14 days after the last dose of investigational product. Females of childbearing potential should only be included in the study after a confirmed menstrual period and a negative highly sensitive urine pregnancy test.
- •Female subjects of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 14 days after the last dose of investigational product.
- •Subject has known sensitivity to any of the products or components to be administered during dosing.
- •Subject likely not to be available to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge.
- •History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
研究组 & 干预措施
Ivabradine
The starting dose of ivabradine was 5 mg twice daily (BID), although investigators had the discretion to start participants at 2.5 mg BID if participant had a history of conduction defects, or bradycardia that could lead to hemodynamic compromise. Dose was adjusted at Day 15 (and at any other clinical visit) between 2.5 - 7.5 mg BID based on heart rate and signs/symptoms of bradycardia.
干预措施: Ivabradine (Drug)
结局指标
主要结局
Change From Baseline in Heart Rate (HR) at Day 57
时间窗: Day1 (baseline), Day 57
Summary is based on observed data, and no imputation is used for missing values. Least-square mean is from the repeated measures model which includes scheduled visits and baseline HR measurement as covariates. The mean change from baseline in heart rate is compared to -5 beats/min which is observed in the placebo group in the Systolic Heart Failure Treatment with the IF Inhibitor Ivabradine Trial (SHIFT) study ( NCT02441218, PMID 20801500).
次要结局
未报告次要终点