Clinical trial NCT01593163: Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus
Official title: Randomised Controlled Clinical Trial of Echocardiographically Guided Versus Standard Ibuprofen Treatment for Patent Ductus Arteriosus: a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Patent Ductus Arteriosus
Keywords: Functional echocardiography
power Doppler cranial ultrasonography
N-terminal probrain natriuretic peptide
Patent ductus arteriosus
Lead sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario la Paz
Sponsor class: OTHER
First posted: 2012-05-08
Enrollment: 49
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: PDA re-opening rate
timeFrame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
Secondary outcomes:
measure: treatment failure
timeFrame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
measure: need for surgical ligation
timeFrame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
measure: need for additional ibuprofen doses
timeFrame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
measure: urine output
timeFrame: 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)
measure: serum creatinine
timeFrame: 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)
measure: mortality
timeFrame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
measure: bronchopulmonary dysplasia
timeFrame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
measure: necrotising enterocolitis
timeFrame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
measure: intraventricular hemorrhage
timeFrame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
measure: White matter damage
timeFrame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
measure: Laser therapy for retinopathy
timeFrame: Infants will be followed for the duration of hospital stay in the Newborn Unit, an expected average of 4-8 weeks
measure: peak systolic velocity
timeFrame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
measure: end-diastolic velocity
timeFrame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
measure: resistance index
timeFrame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
measure: pulsatility index
timeFrame: before each ibuprofen dose should be administered (3 days) and 24 hours after the last dose of ibuprofen was administered
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Department of Neonatology, La Paz University Hospital
Study officials:
affiliation: Department of Neonatology, La Paz University Hospital
name: María Carmen Bravo, PhD MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Neonatology, La Paz University Hospital
name: Fernando Cabañas, PhDMD
role: STUDY_CHAIR
affiliation: Department of Neonatology, La Paz University Hospital
name: Joan Riera, Bio-Engineer
role: STUDY_CHAIR
affiliation: Division of Statistics, La Paz University Hospital. Madrid, Spain.
name: Elia Pérez-Fernández
role: STUDY_CHAIR
affiliation: Department of Neonatology, La Paz University Hospital. Madrid, Spain.
name: José Quero, PhDMD
role: STUDY_CHAIR
affiliation: Department of Neonatology, La Paz University Hospital. Madrid, Spain.
name: Jesús Pérez-Rodríguez, PhDMD
role: STUDY_CHAIR
affiliation: Department of Neonatology, La Paz University Hospital. Madrid, Spain.
name: Adelina Pellicer, PhDMD
role: STUDY_DIRECTOR
References:
citation: Carmo KB, Evans N, Paradisis M. Duration of indomethacin treatment of the preterm patent ductus arteriosus as directed by echocardiography. J Pediatr. 2009 Dec;155(6):819-822.e1. doi: 10.1016/j.jpeds.2009.06.013. Epub 2009 Jul 29.