NCT03808051

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
689

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Jan 2019

Longer than P75 for not_applicable

Geographic Reach
1 country

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 1, 2019

Completed
16 days until next milestone

First Posted

Study publicly available on registry

January 17, 2019

Completed
8 days until next milestone

Study Start

First participant enrolled

January 25, 2019

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 15, 2023

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2025

Completed
Last Updated

November 25, 2025

Status Verified

November 1, 2025

Enrollment Period

4.3 years

First QC Date

January 1, 2019

Last Update Submit

November 20, 2025

Conditions

Preterm InfantBirth, Preterm

Keywords

Preterm infantCord clampingResuscitation

Outcome Measures

Primary Outcomes (1)

  • Intact survival at NICU discharge

    Intact survival is defined as survival without major cerebral injury (IVH ≥ grade 2 and/or PVL ≥ grade 2 and/or periventricular venous infarction) and/or NEC ≥ Bell stage 2.

    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 (6)

  • Rate of treatment failure

    From birth until one hour of age.

  • Short-term neonatal outcomes

    From date of randomization until the date of death or the date of NICU discharge, whichever came first, assessed up to 24 weeks.

  • Short-term maternal outcomes

    From date of randomization until five days after intervention.

  • Neurodevelopmental outcome (Cognitive) at 2 years corrected age

    Assesment at two years corrected age.

  • Neurodevelopmental outcome (Motor) at 2 years corrected age

    Assesment at two years corrected age.

  • +1 more secondary outcomes

Other Outcomes (1)

  • Parental perception and appreciation of stabilisation at birth

    Sent within 1 week after birth.

Study Arms (2)

Physiological-based cord clamping

EXPERIMENTAL

Stabilisation of the infant is performed while the cord is intact and the cord will be clamped after the infant is cardiopulmonary 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%. The maximum cord clamping time is 10 minutes and prior to cord clamping a trial of weaning from PPV to CPAP is performed. With the exception that the infant is stabilised close to the mother and the cord is clamped later, the infant will receive standard resuscitation interventions.

Procedure: Physiological-based cord clamping

Time-based cord clamping

ACTIVE COMPARATOR

Infants are clamped first and then moved to the standard resuscitation table for further treatment and intervention needed for cardiopulmonary stabilisation. Clamping is time based and performed immediately or delayed at 30-60 seconds, depending on the clinical condition of the infant. Uterotonic drugs are administered immediately after cord clamping.

Procedure: Time-based cord clamping

Interventions

Physiological-based cord clampingPROCEDURE

See Arm description.

Physiological-based cord clamping
Time-based cord clampingPROCEDURE

See Arm description.

Time-based cord clamping

Eligibility Criteria

AgeUp to 29 Weeks
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Amsterdam University Medical Centre, location AMC

Amsterdam, Netherlands

Location

Amsterdam University Medical Centre, location VU

Amsterdam, Netherlands

Location

University Medical Centre Groningen

Groningen, Netherlands

Location

Leiden University Medical Centre

Leiden, Netherlands

Location

Maastricht University Medical Centre

Maastricht, Netherlands

Location

Radboud University Medical Centre

Nijmegen, Netherlands

Location

Erasmus Medical Centre - Sophia Children's Hospital

Rotterdam, Netherlands

Location

University Medical Centre Utrecht

Utrecht, Netherlands

Location

Maxima Medical Centre

Veldhoven, Netherlands

Location

Isala Clinics Zwolle

Zwolle, Netherlands

Location

Related Publications (3)

  • Knol R, Brouwer E, van den Akker T, DeKoninck PLJ, Onland W, Vermeulen MJ, de Boode WP, van Kaam AH, Lopriore E, Reiss IKM, Hutten GJ, Prins SA, Mulder EEM, d'Haens EJ, Hulzebos CV, Bouma HA, van Sambeeck SJ, Niemarkt HJ, van der Putten ME, Lebon T, Zonnenberg IA, Nuytemans DH, Willemsen SP, Polglase GR, Steggerda SJ, Hooper SB, Te Pas AB. Physiological versus time based cord clamping in very preterm infants (ABC3): a parallel-group, multicentre, randomised, controlled superiority trial. Lancet Reg Health Eur. 2024 Dec 4;48:101146. doi: 10.1016/j.lanepe.2024.101146. eCollection 2025 Jan.

    PMID: 39717227DERIVED

  • Willemsen SP, Knol R, Brouwer E, van den Akker T, DeKoninck PLJ, Lopriore E, Onland W, de Boode WP, van Kaam AH, Nuytemans DH, Reiss IKM, Hutten GJ, Prins SA, Mulder EEM, Hulzebos CV, van Sambeeck SJ, van der Putten ME, Zonnenberg IA, Te Pas AB, Vermeulen MJ. Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-statistical analysis plan for a multicenter randomized controlled trial. Trials. 2024 Mar 4;25(1):164. doi: 10.1186/s13063-024-08014-y.

    PMID: 38439024DERIVED

  • 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.

    PMID: 36183143DERIVED

MeSH Terms

Conditions

Premature Birth

Condition Hierarchy (Ancestors)

Obstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital Diseases

Study Officials

  • Arjan B Te Pas, Prof

    Leiden University Medical Centre

    STUDY CHAIR

  • Ronny Knol, MD

    Erasmus Medical Centre Rotterdam

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

January 1, 2019

First Posted

January 17, 2019

Study Start

January 25, 2019

Primary Completion

May 15, 2023

Study Completion

May 1, 2025

Last Updated

November 25, 2025

Record last verified: 2025-11

Locations

NL(10)