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Randomized Controlled Trial
. 2021 Sep 15;22(1):627.
doi: 10.1186/s13063-021-05594-x.

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

Tim Hundscheid  1 , Rogier Donders  2 , Wes Onland  3 , Elisabeth M W Kooi  4 , Daniel C Vijlbrief  5 , Willem B de Vries  6 , Debbie H G M Nuytemans  7 , Bart van Overmeire  8 , Antonius L Mulder  9 , Willem P de Boode  10 ; BeNeDuctus trial study group
Collaborators, Affiliations
Randomized Controlled Trial

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

Tim Hundscheid et al. Trials. .

Abstract

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: 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: 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.

Keywords: Bronchopulmonary dysplasia; Ductal ligation; Expectant management; Ibuprofen; Mortality; Necrotising enterocolitis; Neonatal intensive care unit; Patent ductus arteriosus; Prematurity; Statistical analysis plan.

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Conflict of interest statement

Nothing to declare

Figures

Fig. 1
Fig. 1
Consolidated Standards of Reporting Trials (CONSORT) 2010 flow diagram
Fig. 2
Fig. 2
Patient flow of received treatment per treatment allocation group
See this image and copyright information in PMC

References

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