Aeration, Breathing, Clamping Study 3

Study Overview
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Brief Summary
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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).

Official Title
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Physiological-based Cord Clamping in Very Preterm Infants: a Multicentre Randomised Controlled Trial.

Conditions
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Preterm Infant, Birth, Preterm

Intervention / Treatment
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* Procedure: Physiological-based cord clamping
* Procedure: Time-based cord clamping


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 29 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Physiological-based cord clamping<br>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<br>* See Arm description.<br>|
| Active Comparator: Time-based cord clamping<br>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<br>* See Arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | From birth until one hour of age. | 
| Short-term neonatal outcomes | Incidence of prematurity related morbidities during hospital stay. | 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. | 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. | 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. | 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. | Assesment at two years corrected age. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preterm infant, Cord clamping, Resuscitation