Preterm InfantABC3NCT03808051
Aeration, Breathing, Clamping Study 3
A study testing Physiological-based cord clamping and Time-based cord clamping in people with Preterm Infant and Birth, Preterm, run by Leiden University Medical Center at 10 sites in Netherlands.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 29 weeks
- Conditions the study is for
- Preterm Infant, Birth, Preterm
- What is being tested?
- Physiological-based cord clamping and Time-based cord clamping
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 689 participants
- Where
- 10 sitesNetherlands
- Study dates
- 25 Jan 2019to 1 May 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 29 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants born at a gestational age below 30 weeks in a participating centre.
- Parental consent (see 9.2).
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Netherlands10 sites
Amsterdam University Medical Centre, location AMC
Amsterdam
Amsterdam University Medical Centre, location VU
Amsterdam
University Medical Centre Groningen
Groningen
Leiden University Medical Centre
Leiden
Maastricht University Medical Centre
Maastricht
Radboud University Medical Centre
Nijmegen
Erasmus Medical Centre - Sophia Children's Hospital
Rotterdam
University Medical Centre Utrecht
Utrecht
Maxima Medical Centre
Veldhoven
Isala Clinics Zwolle
Zwolle
About this study
Official title: Physiological-based Cord Clamping in Very Preterm Infants: a Multicentre Randomised Controlled Trial.
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.
Read more
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
- Being tested
- Physiological-based cord clamping, Time-based cord clamping
- Keywords
- Preterm infant, Cord clamping, Resuscitation
- Medical subject headings
- Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Physiological-based cord clampingProcedure or surgery
See Arm description.
Time-based cord clampingProcedure or surgery
See Arm description.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Time-based cord clamping |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Treatment failure defined as the number of participants in which abortion of prescribed procedure (intervention or control) occurred and the reasons for abortion.
Measured: From birth until one hour of age.
Short-term neonatal outcomes
Incidence of prematurity related morbidities during hospital stay.
Measured: 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
Incidence of postpartum haemorrhage (> 1000 ml) and surgical site infection after caesarean section.
Measured: From date of randomization until five days after intervention.
Neurodevelopmental outcome (Cognitive) at 2 years corrected age
Neurodevelopmental outcome assessed at 2 years corrected age by the standardized Bayley Scales of Infant Development III (BSID-III-NL), resulting in the Mental Developmental Index. A score of less than 85 (1 SD below the mean of 100) is considered as delayed development.
Measured: Assesment at two years corrected age.
Neurodevelopmental outcome (Motor) at 2 years corrected age
Neurodevelopmental outcome assessed at 2 years corrected age by the standardized Bayley Scales of Infant Development III (BSID-III-NL), resulting in the Performance Developmental Index. A score of less than 85 (1 SD below the mean of 100) is considered as delayed development.
Measured: Assesment at two years corrected age.
Functional outcome at 2 years corrected age
The proportion of participants with cerebral palsy, the proportion of participants with hearing loss requiring hearing aids and the proportion of participants with blindness.
Measured: Assesment at two years corrected age.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2019
- Study start25 Jan 2019
- Primary completion15 May 2023
- Study completion1 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Preterm InfantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 689 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, Medical Research Foundation, The Netherlands, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Responsible party
- Principal investigator, PasABte, Leiden University Medical Center
- Investigators
- Arjan B Te Pas, Prof, Study chair, Leiden University Medical CentreRonny Knol, MD, Principal investigator, Erasmus Medical Centre Rotterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03808051
- Sponsor's protocol ID
- NL67770.058.18
- Acronym
- ABC3
- Status last verified
- Nov 2025
- First submitted
- 1 Jan 2019
- Last updated
- 25 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 39717227Willemsen 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.
PubMed 38439024Knol 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.
PubMed 36183143
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiological-based Cord Clamping in Very Preterm Infants: a Multicentre Randomised Controlled Trial.
- ClinicalTrials.gov ID
- NCT03808051
- Acronym / sponsor ID
- ABC3 / NL67770.058.18
- Conditions
- Preterm Infant, Birth, Preterm
- Keywords
- Preterm infant, Cord clamping, Resuscitation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 689 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, Medical Research Foundation, The Netherlands, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Study start
- 25 Jan 2019 (actual)
- Primary completion
- 15 May 2023 (actual)
- Study completion
- 1 May 2025 (actual)
- First posted
- 17 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Physiological-based cord clamping | Experimental | Procedure: Physiological-based cord clampingStabilisation 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. |
| Time-based cord clamping | Active comparator | Procedure: Time-based cord clampingInfants 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. |
Who may qualify
- Ages
- Up to 29 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Infants born at a gestational age below 30 weeks in a participating centre.
- Parental consent (see 9.2).
Key exclusion criteria (10 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Physiological-based cord clampingSee Arm description. | Procedure or surgery | Physiological-based cord clamping |
| Time-based cord clampingSee Arm description. | Procedure or surgery | Time-based cord clamping |
Primary outcome
Intact survival at NICU discharge
Time frame: From date of randomization until the date of death or the date of NICU discharge, whichever came first, assessed up to 24 weeks.
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.
6 secondary outcomes
Rate of treatment failure
Time frame: From birth until one hour of age.
Short-term neonatal outcomes
Time frame: 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
Time frame: From date of randomization until five days after intervention.
Neurodevelopmental outcome (Cognitive) at 2 years corrected age
Time frame: Assesment at two years corrected age.
Neurodevelopmental outcome (Motor) at 2 years corrected age
Time frame: Assesment at two years corrected age.
Functional outcome at 2 years corrected age
Time frame: Assesment at two years corrected age.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2025.
- Derived from this study: PubMed 39717227Knol 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.
- Derived from this study: PubMed 38439024Willemsen 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.
- Derived from this study: PubMed 36183143Knol 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Arjan B Te Pas, Prof study chair
Leiden University Medical Centre
Ronny Knol, MD principal investigator
Erasmus Medical Centre Rotterdam
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Physiological-based cord clamping and Time-based cord clamping in people with Preterm Infant and Birth, Preterm, run by Leiden University Medical Center at 10 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Intact survival at NICU discharge (time frame: From date of randomization until the date of death or the date of NICU discharge, whichever came first, assessed up to 24 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03808051, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2025.