Clinical trial NCT03808051: Aeration, Breathing, Clamping Study 3
Official title: Physiological-based Cord Clamping in Very Preterm Infants: a Multicentre Randomised Controlled Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Preterm Infant
Birth, Preterm
Keywords: Preterm infant
Cord clamping
Resuscitation
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
name: Medical Research Foundation, The Netherlands
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First posted: 2019-01-17
Enrollment: 689
Sex: ALL
Maximum age (years): 29
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Delayed cord clamping (DCC) in preterm infants results in a decrease in mortality and a trend towards fewer intraventricular haemorrhages. However, preterm infants needing immediate interventions for stabilisation or resuscitation were generally clamped immediately and excluded from trials, while these infants might benefit the most of DCC.

Studies in preterm lambs demonstrated that delaying cord clamping beyond ventilation onset resulted in more stable hemodynamic transition. This approach was called 'physiological-based cord clamping' (PBCC). The hypothesis of this study is that PBCC in preterm infants at birth will lead to an increase in intact survival when compared to standard care.

This study is a multicentre randomised controlled, parallel design, superiority trial, including preterm infants less than 30 weeks of gestation. The intervention is PBCC: stabilisation of the infant with the umbilical cord intact and only clamp the cord when the infant is stable. Stable is defined as the establishment of heart rate greater than 100 bpm and oxygen saturation above 85% while using supplemental oxygen lower than 40%. In the control group cord clamping will be performed time-based: infants are clamped first (at 30-60 seconds if the clinical condition allows) and then moved to the resuscitation table for further stabilisation.

The primary outcome will be intact survival at NICU discharge, defined as survival without cerebral injury (intraventricular haemorrhage ≥ grade 2 and/or periventricular leukomalacia ≥ grade 2 and/or periventricular venous infarction) and/or necrotizing enterocolitis (Bell stage ≥ 2).


Eligibility criteria: Inclusion Criteria:

* Infants born at a gestational age below 30 weeks in a participating centre.
* Parental consent (see 9.2).

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

* Significant congenital malformations influencing cardiopulmonary transition.
* Signs of acute placental abruption.
* Anterior placenta praevia or invasive placentation (accreta/percreta).
* Birth by emergency caesarean section (ordered to be executed within 15 minutes).
* Maternal general anaesthesia during caesarean section.
* Twin gestation with signs of Twin Transfusion Syndrome or Twin Anaemia Polycythemia Syndrome not treated with fetoscopic laser treatment.
* Multiple pregnancy \> 2 (triplets or higher order).
* Decision documented to give palliative neonatal care.

In case of twin delivery by caesarean section it is not possible to perform PBCC in both infants. Both infants will be included: the first infant will receive standard treatment and the second infant will be randomised to either PBCC or standard treatment.

Primary outcomes:
measure: Intact survival at NICU discharge
timeFrame: From date of randomization until the date of death or the date of NICU discharge, whichever came first, assessed up to 24 weeks.
Secondary outcomes:
measure: Rate of treatment failure
timeFrame: From birth until one hour of age.
measure: Short-term neonatal outcomes
timeFrame: From date of randomization until the date of death or the date of NICU discharge, whichever came first, assessed up to 24 weeks.
measure: Short-term maternal outcomes
timeFrame: From date of randomization until five days after intervention.
measure: Neurodevelopmental outcome (Cognitive) at 2 years corrected age
timeFrame: Assesment at two years corrected age.
measure: Neurodevelopmental outcome (Motor) at 2 years corrected age
timeFrame: Assesment at two years corrected age.
measure: Functional outcome at 2 years corrected age
timeFrame: Assesment at two years corrected age.
Other outcomes:
measure: Parental perception and appreciation of stabilisation at birth
timeFrame: Sent within 1 week after birth.
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Centre, location AMC
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Centre, location VU
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen
city: Leiden
country: Netherlands
facility: Leiden University Medical Centre
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Centre
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre - Sophia Children's Hospital
city: Utrecht
country: Netherlands
facility: University Medical Centre Utrecht
city: Veldhoven
country: Netherlands
facility: Maxima Medical Centre
city: Zwolle
country: Netherlands
facility: Isala Clinics Zwolle
Study officials:
affiliation: Leiden University Medical Centre
name: Arjan B Te Pas, Prof
role: STUDY_CHAIR
affiliation: Erasmus Medical Centre Rotterdam
name: Ronny Knol, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Knol R, Brouwer E, van den Akker T, DeKoninck PLJ, Lopriore E, Onland W, Vermeulen MJ, van den Akker-van Marle ME, van Bodegom-Vos L, de Boode WP, van Kaam AH, Reiss IKM, Polglase GR, Hutten GJ, Prins SA, Mulder EEM, Hulzebos CV, van Sambeeck SJ, van der Putten ME, Zonnenberg IA, Hooper SB, Te Pas AB. Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-study protocol for a multicentre randomised controlled trial. Trials. 2022 Oct 1;23(1):838. doi: 10.1186/s13063-022-06789-6.