Randomised Controlled Clinical Trial of Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus: a Pilot Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 49
- 试验地点
- 1
- 主要终点
- PDA re-opening rate
研究概览
简要总结
Patent ductus arteriosus (PDA) is a very common condition in immature newborn babies and it has been associated to morbidity and mortality. Ibuprofen is the drug of choice for PDA treatment according to the last version of the Cochrane review. Nowadays the best dose regimen for ibuprofen remains uncertain. The investigators aim to perform a randomized controlled clinical trial to assess whether echocardiographically guided PDA ibuprofen treatment versus standard treatment could reduce the number of doses of ibuprofen without increasing the reopening rate and reducing the side effects associated to this medication.
详细描述
Patent ductus arteriosus (PDA) is presented in 55 to 70% of the preterm infants with a gestational age lower than 30 weeks or a birth weight lower than 1000 grams. PDA has being associated to mortality or morbidity such as ischemic or hemorrhagic cerebral events, necrotising enterocolitis, renal disfunction or poor pulmonary outcome; however, it is not clear whether these are a consequence of the PDA presence, the treatment implemented for closing it, or the immaturity of these population. PDA standard treatment (ST) consists on three doses of indomethacin or ibuprofen (10-5-5mg/kg) given 24 hours apart, being the surgical closure a second line therapeutic option. In spite of ibuprofen has been pointed as the drug of choice for PDA treatment by the last version of the Cochrane review, side effects have been associated to both medication. Standard ibuprofen treatment is based on a clinical trial where the three-dose protocol seemed to be more effective than one-dose scheme for PDA closure; however, the sample size was not powered to find differences statistically significant, so nowadays the best dose regimen for ibuprofen remains uncertain. Functional echocardiographic assessment is spreading to all over the world. In this scenario, it has been proposed its implementation to guide PDA treatment in order to individualize the number of doses of indomethacin administered as a function of patient's response, limiting the doses and side effects in those where PDA presented an early constriction. The investigators hypothesized whether echocardiographically guided PDA ibuprofen treatment could reduce the number of doses of ibuprofen without increasing the reopening rate and reducing the side effects associated to this medication.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- — 至 1 Month（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Preterm infants with a gestational age lower than 37 weeks of gestational age
- •PDA ≥ 1.5 mm
- •No contraindication to receive ibuprofen
- •Informed consent signed.
排除标准
- •Life-threatening congenital defects
- •Congenital heart disease
- •Contraindication for ibuprofen administration such as oligoanuria < 1cc/kg/h or recent severe intraventricular bleeding (IVH grade III) or creatinine serum level > 1.5 mg/dl or potential intestinal ischemia.
- •Informed consent refused
研究组 & 干预措施
EchoG
Infants in the experimental group (echoG treatment) received additional doses of ibuprofen only if PDA was still ≥ 1.5 mm at the time of the corresponding ibuprofen dose.
干预措施: Ibuprofen EchoG (Drug)
ST (standard treatment)
Infants received 3 doses of ibuprofen at 24-hour intervals, independently of ductal size, as long as additional doses were not contraindicated.
干预措施: Standard ibuprofen treatment (Drug)
结局指标
主要结局
PDA re-opening rate
时间窗: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
PDA re-opening after echocardiographically documented closure, which the attending physician deemed amenable to additional treatment. Infants with ventilator weaning difficulty, protracted metabolic acidosis or persistent hemodynamic instability were included in this category.
次要结局
- treatment failure(Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks)
- need for surgical ligation(Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks)
- need for additional ibuprofen doses(Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks)
- urine output(before the first ibuprofen dose was administered (between 12-72 hours of life) until 24 hours after the last dose of ibuprofen was administered (between 36-168 h of life))
- serum creatinine(before the first ibuprofen dose was administered (between 12-72 hours of life) until 24 hours after the last dose of ibuprofen was administered (between 36-168 h of life))
- mortality(Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks)
- bronchopulmonary dysplasia(Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks)
- necrotising enterocolitis(Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks)
- intraventricular hemorrhage(Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks)
- White matter damage(Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks)
- Laser therapy for retinopathy(Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks)
- peak systolic velocity(before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered)
- end-diastolic velocity(before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered)
- resistance index(before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered)
- pulsatility index(before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered)
研究者
Maria Carmen Bravo Laguna
Principal Investigator
Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz