Multi-centre, randomised non-inferiority trial of early treatment versus expectant management of patent ductus arteriosus in preterm infants (the BeNeDuctus trial): statistical analysis plan.
Bronchopulmonary dysplasia
Ductal ligation
Expectant management
Ibuprofen
Mortality
Necrotising enterocolitis
Neonatal intensive care unit
Patent ductus arteriosus
Prematurity
Statistical analysis plan
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
15 Sep 2021
15 Sep 2021
Historique:
received:
13
04
2021
accepted:
01
09
2021
entrez:
16
9
2021
pubmed:
17
9
2021
medline:
18
9
2021
Statut:
epublish
Résumé
Controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants. A persistent PDA is associated with neonatal mortality and morbidity, but causality remains unproven. Although both pharmacological and/or surgical treatment are effective in PDA closure, this has not resulted in an improved neonatal outcome. In most preterm infants, a PDA will eventually close spontaneously, hence PDA treatment potentially increases the risk of iatrogenic adverse effects. Therefore, expectant management is gaining interest, even in the absence of convincing evidence to support this strategy. The BeNeDuctus trial is a multicentre, randomised, non-inferiority trial assessing early pharmacological treatment (24-72 h postnatal age) with ibuprofen versus expectant management of PDA in preterm infants in Europe. Preterm infants with a gestational age of less than 28 weeks and an echocardiographic-confirmed PDA with a transductal diameter of > 1.5 mm are randomly allocated to early pharmacological treatment with ibuprofen or expectant management after parental informed consent. The primary outcome measure is the composite outcome of mortality, and/or necrotizing enterocolitis Bell stage ≥ IIa, and/or bronchopulmonary dysplasia, all established at a postmenstrual age of 36 weeks. Secondary short-term outcomes are comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. This statistical analysis plan focusses on the short-term outcome and is written and submitted without knowledge of the data. ClinicalTrials.gov NTR5479. Registered on October 19, 2015, with the Dutch Trial Registry, sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28.
Sections du résumé
BACKGROUND
BACKGROUND
Controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants. A persistent PDA is associated with neonatal mortality and morbidity, but causality remains unproven. Although both pharmacological and/or surgical treatment are effective in PDA closure, this has not resulted in an improved neonatal outcome. In most preterm infants, a PDA will eventually close spontaneously, hence PDA treatment potentially increases the risk of iatrogenic adverse effects. Therefore, expectant management is gaining interest, even in the absence of convincing evidence to support this strategy.
METHODS/DESIGN
METHODS
The BeNeDuctus trial is a multicentre, randomised, non-inferiority trial assessing early pharmacological treatment (24-72 h postnatal age) with ibuprofen versus expectant management of PDA in preterm infants in Europe. Preterm infants with a gestational age of less than 28 weeks and an echocardiographic-confirmed PDA with a transductal diameter of > 1.5 mm are randomly allocated to early pharmacological treatment with ibuprofen or expectant management after parental informed consent. The primary outcome measure is the composite outcome of mortality, and/or necrotizing enterocolitis Bell stage ≥ IIa, and/or bronchopulmonary dysplasia, all established at a postmenstrual age of 36 weeks. Secondary short-term outcomes are comorbidity and adverse events assessed during hospitalization and long-term neurodevelopmental outcome assessed at a corrected age of 2 years. This statistical analysis plan focusses on the short-term outcome and is written and submitted without knowledge of the data.
TRIAL REGISTRATION
BACKGROUND
ClinicalTrials.gov NTR5479. Registered on October 19, 2015, with the Dutch Trial Registry, sponsored by the United States National Library of Medicine Clinicaltrials.gov NCT02884219 (registered May 2016) and the European Clinical Trials Database EudraCT 2017-001376-28.
Identifiants
pubmed: 34526095
doi: 10.1186/s13063-021-05594-x
pii: 10.1186/s13063-021-05594-x
pmc: PMC8444433
doi:
Substances chimiques
Ibuprofen
WK2XYI10QM
Banques de données
ClinicalTrials.gov
['NCT02884219']
Types de publication
Equivalence Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
627Subventions
Organisme : ZonMw
ID : 843002622
Pays : Netherlands
Investigateurs
Peter H Dijk
(PH)
Anton H L C van Kaam
(AHLC)
Tessa de Baat
(T)
Koen P Dijkman
(KP)
Eduardo Villamor
(E)
André A Kroon
(AA)
Remco Visser
(R)
Susanne M de Tollenaer
(SM)
Filip Cools
(F)
Marisse Meeus
(M)
Anne-Britt Johansson
(AB)
Frank Derriks
(F)
Catheline Hocq
(C)
Alexandra Zecic
(A)
Tine Brink Henriksen
(TB)
Kasper Jacobsen Kyng
(KJ)
Informations de copyright
© 2021. The Author(s).
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