Multi-center, Randomized Non-inferiority Trial of Early Treatment Versus Expectative Management of Patent Ductus Arteriosus in Preterm Infants (BeNeDuctus Trial - Belgium Netherlands Ductus Trial)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 273
- 试验地点
- 13
- 主要终点
- Composite of mortality, and/or NEC, and/or BPD
研究概览
简要总结
Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age <28 weeks and/or a birth weight ≦1000 grams due to a lack of evidence for or against different approaches. A PDA has been associated with serious complications. However, a common finding is that medical and/or surgical treatment of a PDA seems not to reduce the risk of mortality or major morbidity. This might be related to the fact that a substantial portion of preterm infants are treated unnecessarily, because the ductus arteriosus (DA) might have closed spontaneously without any specific intervention. An expectative approach is gaining interest, although convincing evidence is still missing.
The objective of this study is to investigate whether in preterm infants <28 weeks' gestation with a PDA an expectative management is not inferior to early treatment with regard to the composite of mortality and/or necrotizing enterocolitis (NEC) and/or bronchopulmonary dysplasia (BPD) at a postmenstrual age of 36 weeks.
详细描述
After obtainment of informed consent the first echocardiographic evaluation is performed at a postnatal age of 24-72 hours. In absence of exclusion criteria patients will only be randomized when a PDA is present, the transductal diameter measures >1.5 mm and a blood flow pattern with a predominantly left-to-right shunt is observed. Randomization will assign the neonate to either the medical treatment (COXi) arm or the expectative PDA management arm.
It is essential that neonatal management is similar in both arms with the exception of the prescription of COX-inhibition and routine echocardiographic examination after a course of COXi in the medical treatment arm.
Medical treatment arm When the patient is allocated to the medical treatment arm COX-inhibition is prescribed and started as soon as possible, but no later than 3 hours after the echocardiogram.
The investigators prefer to use Ibuprofen (IBU) for COX-inhibition in this study. Aside from the above mentioned reasons the investigators are confronted with an actual lack of availability of indomethacin in most centers in the Netherlands and Belgium. However, Indomethacin (INDO) can be prescribed for medical ductal closure if this is preferred by a participating center.
The dosing schemes for IBU and INDO are according the local guidelines. For the first week of life the birth weight is used for calculation of the COXi dosage. After a postnatal age of 7 days the actual weight is used for dose calculation, except when the actual weight is still less than the birthweight.
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
- None
入排标准
- 年龄范围
- 1 Hour 至 3 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PDA diameter > 1.5 mm and ductal (predominantly) left-to-right shunt
- •Signed informed consent obtained from parent(s) or representative(s)
- •Gestational age < 28 completed weeks
排除标准
- •Contraindication for administration of cyclooxygenase-inhibitors (COXi)
- •Persistent pulmonary hypertension (ductal right-to-left shunt ≧33% of cardiac cycle)
- •Congenital heart defect, other than PDA and/or patent foramen ovale (PFO)
- •Life-threatening congenital defects
- •Chromosomal abnormalities and/or congenital anomalies associated with abnormal neurodevelopmental outcome
- •Use of COXi prior to randomization
研究组 & 干预措施
Early Treatment with cyclooxygenase inhibitors
Treatment of PDA that starts within the first 3 days of life using cyclooxygenase-inhibitors (Ibuprofen or Indomethacin)
干预措施: Ibuprofen (Drug)
Early Treatment with cyclooxygenase inhibitors
Treatment of PDA that starts within the first 3 days of life using cyclooxygenase-inhibitors (Ibuprofen or Indomethacin)
干预措施: Indomethacin (Drug)
Expectative Treatment
Expectative PDA management is characterized as 'watchful waiting'. No intervention is initiated with the intention to close a PDA.
干预措施: Expectative Management (Other)
结局指标
主要结局
Composite of mortality, and/or NEC, and/or BPD
时间窗: At a postmenstrual age of 36 completed weeks
The primary outcome is the composite of mortality, and/or NEC (Bell stage ≥ IIa), and/or BPD, defined as the need for supplemental oxygen need, all at a postmenstrual age of 36 completed weeks.
次要结局
- Short term sequelae of cardiovascular failure(Day 1 up to 3 months)
- Short term sequelae of adverse events(Day 1 up to 3 months)
- Long-term neurodevelopmental consequences assessed with BSID-III-NL.(Assessed at an corrected age of 2 years)