Multi-center, randomized non-inferiority trial of early treatment versus expectative management of patent ductus arteriosus in preterm infants – The BeNeDuctus Study - (KCE-16013)

Summary (French or English)

Much controversy exists about the optimal management of a patent ductus arteriosus (PDA) in preterm infants, especially in those born at a gestational age <28 weeks and/or a birth weight ≦1000 grams due to a lack of evidence for or against different approaches. A PDA has been associated with serious complications.

However, a common finding is that medical and/or surgical treatment of a PDA seems not to reduce the risk of mortality or major morbidity. This might be related to the fact that a substantial portion of preterm infants are treated unnecessarily, because the ductus arteriosus (DA) might have closed spontaneously without any specific intervention. An expectative approach is gaining interest, although convincing evidence is still missing.

The objective of this study is to investigate whether in preterm infants <28 weeks’ gestation with a PDA an expectative management is as good as an early treatment with regard to the composite of mortality and/or necrotizing enterocolitis (NEC) and/or bronchopulmonary dysplasia (BPD).

This is a multicenter, randomized study that will be conducted in neonatal intensive care units.

Randomization will assign the neonate to either the medical treatment (ibuprofen) arm, in which the intention is to close the DA, or the expectative PDA management arm, in which the DA is considered to be an ‘innocent bystander’.

Infants are followed up till the age of 24 months in this trial.

Trial Description
Title

Multi-center, randomized non-inferiority trial of early treatment versus expectative management of patent ductus arteriosus in preterm infants. (KCE-16013)

Participants (P)

Preterm infants (GA<28 weeks) with an echocardiographic confirmed PDA with a transductal diameter >1.5 mm

Intervention (I)

Expectative PDA management is characterized as ‘watchful waiting’. No intervention is initiated with the intention to close a PD.

Control (C)

The preterm infants with a PDA are treated with COX-inhibition by Ibuprofen

Outcome (O)

The primary outcome is the composite of mortality, and/or NEC (Bell stage ≥ IIa), and/or BPD, defined as the need for supplemental oxygen need, all at a postmenstrual age of 36 completed weeks.

Trial Design

Multicenter, randomized, non-inferiority study conducted in neonatal intensive care units (NICU’s) in the Netherlands and Belgium

Sample Size

564 (150 in BE)

Trial duration

48 Months

Budget

€ 200 000 (incl. VAT)

Status

Recruiting

FPI Q2 2018

 

Trial team

Sponsor

Radboudumc Amalia Children’s Hospital

Chief Investigator

Willem P. de Boode, MD PhD

Radboudumc Amalia Children’s Hospital

Department of Pediatrics, Division of Neonatology

Geert Grooteplein Zuid 10 6525 GA Nijmegen

The Netherlands

Belgian Coordinating Centre

Bart Van Overmeire, MD PhD

Hôpital Erasme

Service de néonatologie

Route de Lennik 808

1070 Bruxelles

Documents
Protocol https://neonatologynetwork.eu/studies/study-protocol
Report

Expected for Q2 2022

Publication

Expected for Q2 2022

References

ClinicalTrials.gov: NCT02884219

EudraCT: 2017-001376-28

Webpage: https://neonatologynetwork.eu/studies/beneductus

Funding scheme

Commissioning workstream 2016