Aeration, Breathing, Clamping Study 3

NCT ID: NCT03808051

Last Updated: 2025-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 689 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-25
• Study Completion Date: 2025-05-01

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).

Conditions

Preterm Infant; Birth, Preterm

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Physiological-based cord clamping

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.

Group Type: EXPERIMENTAL

Physiological-based cord clamping

Intervention Type: PROCEDURE

See Arm description.

Time-based cord clamping

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.

Group Type: ACTIVE_COMPARATOR

Time-based cord clamping

Intervention Type: PROCEDURE

See Arm description.

Interventions

Physiological-based cord clamping

See Arm description.

Intervention Type: PROCEDURE

Time-based cord clamping

See Arm description.

Intervention Type: PROCEDURE

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.

• Maximum Eligible Age: 29 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

Medical Research Foundation, The Netherlands

OTHER

Sponsor Role: collaborator

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

PasABte

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Arjan B Te Pas, Prof

Role: STUDY_CHAIR

Leiden University Medical Centre

Ronny Knol, MD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Centre Rotterdam

Locations

Amsterdam University Medical Centre, location AMC

Amsterdam, , Netherlands

Amsterdam University Medical Centre, location VU

Amsterdam, , Netherlands

University Medical Centre Groningen

Groningen, , Netherlands

Leiden University Medical Centre

Leiden, , Netherlands

Maastricht University Medical Centre

Maastricht, , Netherlands

Radboud University Medical Centre

Nijmegen, , Netherlands

Erasmus Medical Centre - Sophia Children's Hospital

Rotterdam, , Netherlands

University Medical Centre Utrecht

Utrecht, , Netherlands

Maxima Medical Centre

Veldhoven, , Netherlands

Isala Clinics Zwolle

Zwolle, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 39717227 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38439024 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36183143 (View on PubMed)

Other Identifiers

NL67770.058.18

Identifier Type: -

Identifier Source: org_study_id