Clinical trial NCT04282941: Clinical Trial to Evaluate Two Guidelines for the Administration of Ibuprofen in the Treatment of Persistent Ductus Arteriosus Eco-guided: Impact in the Intestinal Prognosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Persistent Ductus Arteriosus
Lead sponsor: Instituto de Investigación Hospital Universitario La Paz
Sponsor class: OTHER
First posted: 2020-02-25
Enrollment: 180
Sex: ALL
Minimum age (years): 0
Maximum age (years): 33
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Administration schedule A: Ibuprofen in continuous iv infusion and EchoG. Each cycle will be 3 doses.

Administration schedule B: slow iv bolus Ibuprofen and EchoG. Each cycle will be 3 doses.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: 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
timeFrame: 40 weeks
Secondary outcomes:
measure: To Identify genetic polymorphisms asociated to refractory medical treatment of AD and in those most vulnerable to presenting necrotizing enterocolitis or isolated intestinal perforation.
timeFrame: Day 0(Visit 1)
Other outcomes:
measure: To Assess the incidence of neonatal morbidity associated with each of the forms of treatment
timeFrame: up to 40 Weeks Postmenstrual age
measure: To Assess the neonatal mortality associated with each of the forms of treatment
timeFrame: up to 40 Weeks Postmenstrual age
Locations:
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Quirón Salud Madrid
Study officials:
References: