Phase III Clinical Trial, Randomized, Multicentre, Double Blind to Evaluate Two Guidelines for the Administration of Ibuprofen in the Treatment of Persistent Ductus Arteriosus Eco-guided: Impact in the Intestinal Prognosis
试验速览
- 阶段
- 3 期
- 入组人数
- 180
- 试验地点
- 3
- 主要终点
- Change the incidence of necrotizing enterocolitis or isolated intestinal perforation in preterm infants receiving treatment for closure of AD with ibuprofen in continuous IV perfusion and EchoG vs iv and EchoG boluses
研究概览
简要总结
Persistent ductus arteriosus (DA) is a common entity in the premature newborn and is associated with high morbidity and mortality. There is still controversy about which is the best treatment for its closure. Children with AD who receive pharmacological treatment present more frequently than other premature children, necrotizing enterocolitis or isolated intestinal perforation.
At the present time, the conventional treatment of DA consists in the administration of intravenous ibuprofen, slow bolus in 3 daily doses 10-5-5 mg / kg / day. Recently, it has been observed that treatment with ibuprofen in continuous iv infusion for 3 days seems to be more effective in closing DA than conventional treatment for 3 days with the same dose but in slow iv bolus. This experimental treatment reduced the incidence of associated necrotizing enterocolitis. Our group demonstrated in a previous pilot trial that the guided treatment with echocardiography (EchoG) of DA with ibuprofen compared with conventional treatment, allows to reduce the number of doses to the patient. The EchoG treatment thus presents a potential reduction of side effects associated with medication, this resulted in a tendency to have a lower incidence of necrotising enterocolitis in the experimental group. This multicenter clinical trial aims to test the hypothesis that the combination of 2 experimental treatments, the use of ibuprofen in continuous perfusion and EchoG, reduces the incidence of digestive side effects (necrotising enterocolitis or isolated intestinal perforation) compared to the treatment also guided by echocardiography but slow bolus iv.
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
- Double (Participant, Investigator)
盲法说明
A randomized system with closed envelopes will be designed in which patients will be assigned to one of the 2 treatment groups, stratified by gestational age (<28 weeks and ≥28 weeks) and by hospital center. In each center and each stratum, they will be randomly assigned in a 1: 1 ratio to each group of study. The assignment will be sequential.
The doctors responsible for the patient will be blind to the intervention but will be responsible for the sealed envelopes, and at the time of patient randomization, will deliver the sealed envelope corresponding to the nurses responsible for the preparation of the medication.
入排标准
- 年龄范围
- 0 Minutes 至 33 Weeks（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Preterm infants with less 33 weeks of gestational age
- •DA ≥ 1.5 mm with decision to start pharmacological treatment
- •Informed consent signed by the legal representative
排除标准
- •Consent denied
- •Presence of serious congenital alterations
- •Congenital heart disease
- •Contraindication for the administration of IB: oligoanuria (diuresis <1cc / kg / h), bleeding severe recent intraventricular (HIV grade III or extensive periventricular hemorrhagic infarction), serum creatinine> 1.5 mg / dl or clinical suspicion of intestinal ischemia.
研究组 & 干预措施
Ibuprofen in continuous (24 hours) iv infusion and EchoG
The first dose of ibuprofen will be 10 mg / kg to be administered as a continuous infusion for 24 hours. An echocardiogram will be performed before each of the following 2 doses of 5 mg / Kg and will only be administered if it meets echocardiographic criteria that indicate open DA (observation of ductus permeability with color Doppler regardless of its size). Each dose will be administered as a 24-hour continuous infusion.
干预措施: Ibuprofen in continuous (24 hours) iv infusion and EchoG (Drug)
IV bolus Ibuprofen slow (15 minutes) and EchoG
The first dose of ibuprofen of 10 mg / Kg to be administered in slow iv bolus (15 minutes). Before each of the following 2 doses of 5 mg / Kg, echocardiography will be performed and will only be administered if it meets the echocardiographic criteria indicated by open DA (observation of ductus permeability in color Doppler regardless of its size). Each dose will be administered in iv boluses in 15 minutes
干预措施: IV bolus Ibuprofen slow (15 minutes) and EchoG (Drug)
结局指标
主要结局
Change the incidence of necrotizing enterocolitis or isolated intestinal perforation in preterm infants receiving treatment for closure of AD with ibuprofen in continuous IV perfusion and EchoG vs iv and EchoG boluses
时间窗: 40 weeks
Change the incidence of necrotizing enterocolitis or isolated intestinal perforation in preterm infants receiving treatment for closure of AD with ibuprofen in continuous IV perfusion and EchoG vs iv and EchoG boluses
次要结局
- To Identify genetic polymorphisms asociated to refractory medical treatment of AD and in those most vulnerable to presenting necrotizing enterocolitis or isolated intestinal perforation.(Day 0(Visit 1))