Randomized Non-inferiority Trial of Early Treatment Versus Expectant Management of Patent Ductus Arteriosus in Preterm Infants
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 208
- 试验地点
- 1
- 主要终点
- Incidence of bronchopulmonary dysplasia (BPD) or mortality at 36 weeks postmenstrual age (PMA)
研究概览
简要总结
Patent ductus arteriosus (PDA) in very preterm newborns is associated with severe neonatal mor-bidity: intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing en-terocolitis (NEC), retinopathy of prematurity (ROP). Existing methods of management PDA do not reduce the incidence of these diseases. The efficacy of cyclooxygenase inhibitors (COX) which are currently the standard of treatment in extreme preterm infants is about 70-80%. COX inhibitors have significant side effects. On the other hand, surgical ligation of the ductus arteriosus is associated with deterioration due to cardio-pulmonary problems and long-term complications. Paracetamol has been proposed for treatment of hemodynamically significant PDA because it has a different mecha-nism of action compared with COX inhibitors and a better safety profile.
Recently, expectant approach has becoming more popular, although there is not enough evidence to support it.
The objective of this study is to investigate whether in preterm infants, born at a GA less than 32 weeks, with a PDA (diameter > 1.5 mm) at a postnatal age of < 72 h, an expectant management is non-inferior to early treatment with regard to the composite of mortality and/or severe morbidity.
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
- — 至 3 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Gestational age < 32 weeks
- •Birthweight <1500 g
- •Age less than 72 hours
- •PDA diameter > 1.5 mm
- •Signed informed consent obtained from both parents
排除标准
- •Birthweight ≥ 1500 g and/or gestation age ≥ 32 weeks
- •Lack of informed consent of the parents
- •Congenital heart defect, other than PDA and/or patent foramen ovale (PFO)
- •The presence of a clinically apparent hemorrhagic syndrome
- •Any intraventricular hemorrhage (IVH) in the first 48 hours or IVH grade 3-4
- •A platelet count of < 50,000/mm3
- •A serum creatinine concentration of > 110 μmol/L
- •Oliguria <1 ml/kg/h
- •Suspected/apparent NEC
- •Suspected/apparent lung hypoplasia
研究组 & 干预措施
Rectal ibuprofen
Early treatment of PDA that starts within the first 3 days of life using rectal ibuprofen q24h for 3 days, dosages: 20 mg/kg + 10 mg/kg + 10 mg/kg
干预措施: Ibuprofen (Drug)
Intravenous paracetamol
Early treatment of PDA that starts within the first 3 days of life using intravenous paraceta-mol 15 mg/kg q6h for 3 days
干预措施: Paracetamol (Drug)
Expectant Treatment
Expectant PDA management is characterized as 'watchful waiting'. No intervention is initiated with the intention to close a PDA unless defi-nitely needed based of the predefined infant's condition.
干预措施: Expectant Management (Other)
结局指标
主要结局
Incidence of bronchopulmonary dysplasia (BPD) or mortality at 36 weeks postmenstrual age (PMA)
时间窗: 36 weeks PMA
次要结局
- Incidence of severe intraventricular hemorrhage(28-days since birth)
- Closure rate of PDA within a week after the first and second course of pharmacological treatment(Participants will be evaluated at the end of first and second course, at an expected avarage of 10 days of life)
- Mortality rate(36 weeks PMA)
- The need for surgical ductus closure(Day 1 up to 3 month)
- Duration of any ventilation assist(Day 1 up to 3 month)
- Incidence of necrotizing enterocolitis (Bell stage ≥ IIa)(36 weeks PMA)
- PDA re-opening rate(Day 1 up to 3 month)
- Incidence of BPD(36 weeks PMA)
- Duration of oxygen supplementation(Day 1 up to 3 month)
- Incidence of periventricular leukomalacia(36 weeks PMA)
- Age of administration of full volume of enteral nutrition(Day 1 up to 3 month)
- Incidence of oliguria(In the first 14 days of life)
- Incidence of hypotension(Day 1 up to 3 month)
研究者
Dmytro Dobryanskyy
Clinical Professor
Lviv National Medical University