TY - JOUR
T1 - Early treatment versus expectative management of patent ductus arteriosus in preterm infants: a multicentre, randomised, non-inferiority trial in Europe (BeNeDuctus trial)
AU - Hundscheid, Tim
AU - Onland, Wes
AU - van Overmeire, Bart
AU - Dijk, Peter
AU - van Kaam, Anton H. L. C.
AU - Dijkman, Koen P.
AU - Kooi, Elisabeth M. W.
AU - Villamor, Eduardo
AU - Kroon, Andre A.
AU - Visser, Remco
AU - Vijlbrief, Daniel C.
AU - de Tollenaer, Susanne M.
AU - Cools, Filip
AU - van Laere, David
AU - Johansson, Anne-Britt
AU - Hocq, Catheline
AU - Zecic, Alexandra
AU - Adang, Eddy
AU - Donders, Rogier
AU - de Vries, Willem
AU - van Heijst, Arno F. J.
AU - de Boode, Willem P.
PY - 2018/8/4
Y1 - 2018/8/4
N2 - Background: Much controversy exists about the optimal management of a patent ductus arteriosus (FDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a FDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. Methods: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage >= IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. Discussion: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks.
AB - Background: Much controversy exists about the optimal management of a patent ductus arteriosus (FDA) in preterm infants, especially in those born at a gestational age (GA) less than 28 weeks. No causal relationship has been proven between a (haemodynamically significant) PDA and neonatal complications related to pulmonary hyperperfusion and/or systemic hypoperfusion. Although studies show conflicting results, a common understanding is that medical or surgical treatment of a FDA does not seem to reduce the risk of major neonatal morbidities and mortality. As the PDA might have closed spontaneously, treated children are potentially exposed to iatrogenic adverse effects. A conservative approach is gaining interest worldwide, although convincing evidence to support its use is lacking. Methods: This multicentre, randomised, non-inferiority trial is conducted in neonatal intensive care units. The study population consists of preterm infants (GA < 28 weeks) with an echocardiographic-confirmed PDA with a transductal diameter > 1.5 mm. Early treatment (between 24 and 72 h postnatal age) with the cyclooxygenase inhibitor (COXi) ibuprofen (IBU) is compared with an expectative management (no intervention intended to close a PDA). The primary outcome is the composite of mortality, and/or necrotising enterocolitis (NEC) Bell stage >= IIa, and/or bronchopulmonary dysplasia (BPD) defined as the need for supplemental oxygen, all at a postmenstrual age (PMA) of 36 weeks. Secondary outcome parameters are short term sequelae of cardiovascular failure, comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. Consequences regarding health economics are evaluated by cost effectiveness analysis and budget impact analysis. Discussion: As a conservative approach is gaining interest, we investigate whether in preterm infants, born at a GA less than 28 weeks, with a PDA an expectative management is non-inferior to early treatment with IBU regarding to the composite outcome of mortality and/or NEC and/or BPD at a PMA of 36 weeks.
KW - Prematurity
KW - Patent ductus arteriosus
KW - Neonatal intensive care unit
KW - Ibuprofen
KW - Expectative management
KW - Ductal ligation
KW - Mortality
KW - Necrotising enterocolitis
KW - Bronchopulmonary dysplasia
KW - Cost-effectiveness
KW - LOW-BIRTH-WEIGHT
KW - PLACEBO-CONTROLLED TRIAL
KW - PROPHYLACTIC INDOMETHACIN THERAPY
KW - RESPIRATORY-DISTRESS SYNDROME
KW - BUDGET IMPACT ANALYSIS
KW - PREMATURE-INFANTS
KW - DOUBLE-BLIND
KW - INTRAVENOUS IBUPROFEN
KW - EARLY CLOSURE
KW - BLOOD-FLOW
U2 - 10.1186/s12887-018-1215-7
DO - 10.1186/s12887-018-1215-7
M3 - Article
C2 - 30077184
SN - 1471-2431
VL - 18
JO - Bmc Pediatrics
JF - Bmc Pediatrics
IS - 1
M1 - 262
ER -