An International Multicentre Open-label Comparative Therapeutic Exploratory Trial to Investigate the Role of a New Neonatal Formulation of Dobutamine in the Treatment of Haemodynamic Insufficiency in the Immediate Postnatal Period
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Half-life of the neonatal formulation of dobutamine.
研究概览
简要总结
Haemodynamic insufficiency after birth is seen commonly in babies born prematurely and is associated with adverse outcomes. In current clinical practice, a combination of blood pressure and clinical signs is used to guide therapy. However, blood pressure is a poor surrogate of systemic and organ (brain) blood flow distribution during transitional circulation. This state is characterised by increased peripheral vascular resistance and increased afterload causing myocardial depression and impaired blood flow distribution in spite of 'normal' blood pressure. Echocardiography-Doppler (Echo-D) measurement of superior vena cava (SVC) flow has been proposed as a more clinically relevant marker of circulatory impairment shortly after birth than systemic hypotension. When there is low SVC flow, several small-scale clinical trials have suggested dobutamine as the optimal therapeutic option. However the associations between SVC flow and short- and long- term outcomes are not strong enough to allow SVC flow alone to be the basis for the inclusion of patients into a confirmatory trial to demonstrate the efficacy and safety of dobutamine.
NeoCirc-001 - The primary objective is to answer some important questions required for the design of a subsequent placebo-controlled trial (NeoCirc-003), which will evaluate the effectiveness of a new neonatal formulation of dobutamine to treat haemodynamic insufficiency in the first 72 hours after birth in babies born at less than 33 weeks' gestation. Observational data will be collected from this population with a view to determining the degree to which diagnostic measures influence treatment decisions. The primary outcome is death or worst cranial ultrasound (CUS) appearance at or before 36 weeks' gestation.
NeoCirc-001A - The primary objective is to estimate the elimination half-life, and consequently the time to steady-state of dobutamine in extremely premature neonates.
NeoCirc-001B - The primary objective is to construct a population pharmacokinetic pharmacodynamic model that will be validated using samples collected during the confirmatory trial (NeoCirc-003).
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
- — 至 72 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •NeoCirc-001, 001A and 001B -
- •non-viability;
- •congenital hydrops or malformations likely to affect cardiovascular adaptation;
- •surgery planned within 72 hours of birth;
- •chromosomal anomalies;
- •informed consent form (ICF) not signed.
研究组 & 干预措施
Dobutamine
Infants who meet the definition of poor perfusion state will be treated at the discretion of the responsible physician following the standard local policies. The interventions will be dobutamine from a new neonatal formulation developed for NeoCirc and/or other treatments (including any other cardiovascular drug or volume replacement with normal saline).
干预措施: Dobutamine (Drug)
结局指标
主要结局
Half-life of the neonatal formulation of dobutamine.
时间窗: The first sample will be drawn after the end of the infusion, at the time when dobutamine ceases. The second sample will be taken at different study time points after the end of infusion (from 5 min to 6 hours).
NeoCirc-001A: Half-life of the neonatal formulation of dobutamine. The first sample will be drawn after the end of the infusion, at the time when dobutamine ceases reaching the systemic circulation of the neonate, defined as time end (te). To calculate the end of infusion (te) the dead space used in each unit will be taken into account (see below). The second sample will be taken at different study time points after the end of infusion: * 5 min after te * 15 min after te * 45 min after te * 2 hours after te * 6 hours after te Two infants will be allocated to each time point. Sampling times will be assigned randomly to the patients.
Mortality, or intraventricular haemorrhage (IVH) grades 3 or 4, or cystic and non-cystic periventricular leukomalacia (PVL), or porencephalic cysts, ventriculomegaly, or cerebellar haemorrhage.
时间窗: at 36 (+/-2 weeks) postmenstrual age
A composite endpoint is defined as follows: treatment failure is when one of the following is true at or before gestational age 36 (+/-2 weeks), when all surviving patients will have a cranial ultrasound (CUS)- 1. Neonate dies, or 2. Intraventricular haemorrhage (IVH) grades 3 or 4, or 3. cystic and non-cystic periventricular leukomalacia (PVL), or 4. porencephalic cysts, ventriculomegaly, or cerebellar haemorrhage.
次要结局
- Nosocomial infection(From birth to 36 (+/-2 weeks) postmenstrual age)
- Patent ductus (PDA)(From birth to 36 (+/-2 weeks) postmenstrual age)
- Retinopathy of prematurity(at 36 (+/-2 weeks) postmenstrual age)
- early infection(From birth to 72 hours after birth)
- Capillary refill time(First 72 hours of life (data collection every 9 ±3 hrs))
- Hypertension(From birth to 36 (+/-2 weeks) postmenstrual age)
- Superior vena cava flow(First 72 hours of life (data collection every 9 ±3 hrs))
- Blood lactate concentration(First 72 hours of life (data collection every 9 ±3 hrs))
- Background pattern(First 72 hours of life (data collection every 6 ±1 hrs))
- Right cardiac output(First 72 hours of life (data collection every 9 ±3 hrs))
- Interburst interval (IBI)(First 72 hours of life (data collection every 6 ±1 hrs))
- Presence of abnormal transients(First 72 hours of life (data collection every 6 ±1 hrs))
- Hypotension(From birth to 36 (+/-2 weeks) postmenstrual age)
- Urine output(First 72 hours of life (data collection every 9 ±3 hrs))
- Mortality(From birth to 36 (+/-2 weeks) postmenstrual age)
- Arterial blood pressure(First 72 hours of life (data collection every 9 ±3 hrs))
- Base excess(First 72 hours of life (data collection every 9 ±3 hrs))
- cerebral regional tissue oxygen saturation (rStO2)(First 72 hours of life (data collection every 6 ±1 hrs))
- Cerebral fractional oxygen extraction (FOE)(First 72 hours of life (data collection every 6 ±1 hrs))
- Intraventricular haemorrhage 2-4(From birth to 36 (+/-2 weeks) postmenstrual age)
- Survival free of severe brain injury(From birth to 36 (+/-2 weeks) postmenstrual age)
- Discontinuity(First 72 hours of life (data collection every 6 ±1 hrs))
- Amplitude(Fist 72 hours of life (data collection every 6 ±1 hrs))
- Synchrony(First 72 hours of life (data collection every 6 ±1 hrs))
- Necrotizing enterocolitis(From birth to 36 (+/-2 weeks) postmenstrual age)
- Chronic lung disease(at 36 (+/-2 weeks) postmenstrual age)
- Oxygen-dependency at discharge(At discharge)
研究者
Adelina Pellicer
Chief Investigator
Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz