A Monocentric, Open Label, Single Arm, Pilot Study on the Early Administration of Ivabradine in Children Aged >6 Months and <18 Years With Dilated Cardiomyopathy and Acute Heart Failure
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of maintenance
研究概览
简要总结
This is a monocentric, prospective, single arm, not for profit study. It is designed to study the early use of ivabradine in patients with dilated cardiomyopathy and Ejection Fraction (EF) < 45%.
详细描述
The study is divided into a screening and enrollment visit (V1) where eligibility for treatment will be confirmed. Ivabradine will be administered to eligible patients with increasing dosage during the titration period (TP) which will last from a minimum of 3 days to a maximum of 15 days. This will be followed by a maintenance period (MP) of the drug for a further 14 days. The follow-up period (FU) will last 4 months.
The dose of ACE inhibitors will be introduced after 72 hours of clinical stability after the introduction of titrated ivabradine at maximum dose according to protocol. The anti-aldosterone will be introduced 24 hours after the introduction of ivabradine. The diuretic will not be modified during the titration phase of the drug, unless there is clinical necessity.
During the FU ivabradine will be continued at stable dosage, in order to maintain the target heart rate (HR) reached during the maintenance phase (HR > 80 bpm, in the group of patients older than 6-12 months, or HR > 70 bpm in patients aged 1-3 years or HR > 50 bpm between 3-18 years). In all patients, the drug dose will be decreased or discontinued in case of bradycardia (HR< 80 bpm in patients 6-12 months, HR< 70 bpm in patients 1-3 years of age or HR< 60 bpm in patients 3-18 years of age) and/or symptoms related to bradycardia or for other safety reasons.
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
- 6 Months 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Dilated cardiomyopathy defined according to the indications of the Cardiomyopathy Task Force (dilation > 2 Standard Deviations (SD) and hypokinesia);
- •Class NYHA/Ross ≥ II;
- •Ejection fraction < 40%;
- •Patients with acute heart failure episodes (both new episode and relapse) in the last three months;
- •Systolic blood pressure > 50° age and height;
- •Heart rate: 6-12 months: ≥105 bpm, >1 year <3 years: ≥95 bpm, 3-5 years: ≥75 bpm, 5-18 years: >70 bpm.
排除标准
- •Cardiogenic shock in the three months;
- •Hypertrophic, restrictive or mixed cardiomyopathy;
- •Acute lymphocytic myocarditis diagnosed with endomyocardial biopsy;
- •Significant Valvular Pathology;
- •Sinus block and congenital long QT syndrome;
- •Atrial Fibrillation;
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels > 2.5 times normal, bilirubin > 3 and creatinine > 2.5 mg/dL;
- •Pregnancy and/or positive pregnancy test patients;
- •Hypersensitivity to the active substance or any of the excipients;
- •Participation in a clinical trial in which an experimental drug was administered within 30 days or 5 half-lives of the investigational drug;
- •Chronic lung disease or other clinical condition that the investigating physician believes is incompatible with the study;
- •eGFR <15 mL/min/1.73 m2.
研究组 & 干预措施
Ivabradine
Eligible patients will be given treatment with ivabradine during a titration period which will last from a minimum of 3 days to a maximum of 15 days. This will be followed by a maintenance period of another 14 days. At the end of maintenance period, primary endpoint will be assessed. After maintenance period, the patient will continue ivabradine at the same dosage during a follow-up period that will last 4 months.
干预措施: Ivabradine 5Mg Tab (Drug)
结局指标
主要结局
Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of maintenance
时间窗: At the end of the two weeks maintenance period (17-29 days from enrollment)
To assess the response to ivabradine on heart rate after 14 days of stable therapy
次要结局
- Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of follow-up(At the end of the 16 weeks follow-up period (129-141 days from enrollment))
- Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of follow-up(At the end of the 16 weeks follow-up period (129-141 days from enrollment))
- Left ventricular function, calculated by 2D echocardiographic technique (calculation of left ventricular volume and ejection fraction - mean (±SD) difference from baseline) at the end of maintenance(At the end of the two weeks maintenance period (17-29 days from enrollment))
- Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of maintenance(At the end of the two weeks maintenance period (17-29 days from enrollment))
- Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of maintenance(At the end of the two weeks maintenance period (17-29 days from enrollment))
- Use of inotropic drugs (number and % of patients who had to use inotropes at the end of follow-up)(At the end of the 16 weeks follow-up period (129-141 days from enrollment))
- Number and % of dropouts at the end of maintenance(At the end of the two weeks maintenance period (17-29 days from enrollment))
- Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of follow-up(At the end of the 16 weeks follow-up period (129-141 days from enrollment))
- Number and % of dropouts at the end of follow-up(At the end of the 16 weeks follow-up period (129-141 days from enrollment))
- Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of maintenance(At the end of the two weeks maintenance period (17-29 days from enrollment))
- Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of follow-up(At the end of the 16 weeks follow-up period (129-141 days from enrollment))
- Use of inotropic drugs (number and % of patients who had to use inotropes at the end of maintenance)(At the end of the two weeks maintenance period (17-29 days from enrollment))
- Time (days) from start of ivabradine therapy and new episode of acute heart failure, and/or implantation of mechanical assist device at the end of follow up(At the end of the 16 weeks follow-up period (129-141 days from enrollment))
- Left ventricular function, calculated by 2D echocardiographic technique (calculation of left ventricular volume and ejection fraction - mean (±SD) difference from baseline) at the end of follow-up(At the end of the 16 weeks follow-up period (129-141 days from enrollment))
研究者
Rachele Adorisio
MD
Bambino Gesù Hospital and Research Institute