To compare the effect of umbilical cord clamping after cardiopulmonary stabilisation (Physiological Based Cord Clamping; PBCC) to standard care (Time Based Cord Clamping; TBCC) on intact survival and health care costs in preterm infants.
ID
Source
Brief title
Condition
- Neonatal and perinatal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The dichotomous outcome intact survival at NICU discharge 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.
Secondary outcome
1. Procedure related
Details of the stabilisation at birth, treatment failure, infant temperature at
admission to the NICU, highest infant haemoglobin levels within 24 hours of
age, occurrence of polycythemia.
2. Neonatal outcomes, short-term
Apgar scores, ductal flow ratio at 1 hour of age combined with blood pressure
measurement, intubation in first 72 hours, IRDS, use of surfactant,
intravascular volume expansion in first 72 hours, inotropes in first 72 hours,
pneumothorax, persistent ductus arteriosus for which medical intervention or
surgical ligation is necessary, duration of phototherapy, proven early onset
sepsis (clinical suspicion with positive blood culture), proven late onset
sepsis (clinical suspicion with positive blood culture > 72 hours after
delivery), necrotizing enterocolitis >= grade 2, surgical NEC: Necrotizing
enterocolitis requiring surgical intervention (also if the patient was too
unstable to undergo surgery), spontaneous focal intestinal perforation, number
of red blood cell transfusions, intraventricular haemorrhage >= grade 2,
periventricular leukomalacia >= grade 2, periventricular venous infarction,
bronchopulmonary dysplasia, retinopathy of prematurity, mortality at 28 days
postnatal age (PNA), 36 weeks postmenstrual age (PMA) and at hospital
discharge, length of stay in NICU, length of stay in hospital
3. Maternal outcomes
Maternal blood loss, postpartum haemorrhage > 1000 ml, placental weight,
surgical site infection after caesarean section.
4. Neonatal outcomes, long-term
Long-term neurodevelopmental outcomes assessed at 2 years corrected age:
o Bayley Scales of Infant Development III (BSID-III-NL)
o Mental Developmental Index (MDI)
o Psychomotor Developmental Index (PDI)
o Cerebral palsy and severity of CP
o Hearing loss requiring hearing aids
o Blindness
o Behavioural problems (CBCL)
The parents and the caregivers will be asked to fill in a questionnaire
concerning their perception and appreciation of the approach during birth and
the stabilisation stage.
5. Secondary outcomes, cost-effectiveness:
Total (re)-admission days, other healthcare use (e.g. outpatient visits, home
therapy (such as tube feeding), paramedical care, GP visits), non-medical costs
children (e.g. day-care), productivity losses parents, quality of life
children, quality of life parents.
Background summary
Preterm infants could benefit from placental transfusion (blood transfer from
the placenta to the infant) when cord clamping is delayed. A recent
meta-analysis comparing delayed cord clamping (DCC) with immediate cord
clamping in preterm infants showed a decrease in mortality and a trend towards
fewer intraventricular haemorrhages. However, in most studies DCC was performed
at a fixed time point of 30-60 seconds after birth, while placental transfusion
is only complete after 3 minutes. In addition, preterm infants needing
immediate interventions for stabilisation or resuscitation were clamped
immediately and excluded from analysis, while these infants might benefit the
most of DCC.
While the rationale of all cord clamping studies was to allow for placental
transfusion, studies in preterm lambs recently demonstrated that delaying cord
clamping beyond ventilation onset also prevents a significant drop in cardiac
output. This approach avoided large disturbances in systemic and cerebral
haemodynamics and concomitant bradycardia and hypoxia. Avoiding these adverse
effects may decrease the risk of cerebral injury and hypoxia-related diseases
such as necrotizing enterocolitis and associated rates of mortality and
morbidity in preterm infants.
These adverse effects described above may be avoided when preterm infants are
first stabilised with an intact cord and clamping is postponed until the infant
is considered cardiopulmonary stable. We called this approach *physiological-
based cord clamping* (PBCC), since the moment of cord clamping is based on the
clinical condition of the infant. Until now PBCC was practically not possible
since the cord needed to be clamped in order to move the infant to the
resuscitation table. The recent development of a new purpose-built
resuscitation table (the Concord) in Leiden makes it possible to provide all
the necessary interventions for cardiopulmonary stabilisation, while the cord
remains intact. A recent safety and feasibility study in preterm infants showed
that PBCC using the Concord was feasible and safe. We observed a reduction of
the incidence of bradycardia and hypoxia at birth, supporting the earlier
observed increased stability during haemodynamic transition in animal studies.
In addition, average cord clamping time exceeded 4 minutes, which allows
preterm infants to benefit from a more complete and optimal placental
transfusion.
We hypothesize that PBCC in preterm infants at birth will lead to an increase
in intact survival (survival without cerebral injury and/or necrotizing
enterocolitis) when compared to standard care.
Study objective
To compare the effect of umbilical cord clamping after cardiopulmonary
stabilisation (Physiological Based Cord Clamping; PBCC) to standard care (Time
Based Cord Clamping; TBCC) on intact survival and health care costs in preterm
infants.
Study design
Multicentre randomised controlled trial, parallel design, superiority trial.
Intervention
Physiological-Based Cord Clamping (PBCC); stabilisation of the infant with the
umbilical cord intact and only clamp the cord when the infant is
cardiopulmonary stable using a purpose-built resuscitation table, the Concord.
Study burden and risks
In this study most preterm infants need stabilisation at birth and might
benefit from delayed cord clamping. Delayed cord clamping has been incorporated
in international guidelines, mostly using a fixed time and delaying
stabilisation until the cord has been clamped. Currently, studies are performed
where stabilisation is performed while the cord remains intact using
commercially available resuscitation tables. So far, stabilisation with the
cord intact has been considered a safe approach, vaginally as well as during
caesarean section.
The infant has potentially more benefit from delaying cord clamping when PBCC
is used. We do not expect that there is an added risk as the Concord is fully
equipped for stabilisation and resuscitation. The earlier studies did not show
any additional risks for the mother or the infant. Secondary outcomes include
*safety parameters* for the mother and the infant. While the mother will
benefit for having her baby close to her and able to touch her baby, there is a
risk that it will cause anxiety as interventions take place close to the
parents. We will minimize this by communicating to the parents antenatally what
to expect and during the stabilisation the nurse will communicate what happens
during the stabilisation.
Stabilisation at birth of preterm infants occurs exclusively in this patient
group. Any intervention to reduce the risks in these patient group therefore
needs to be studied in this specific population.
Albinusdreef 2 .
Leiden 2333 ZA
NL
Albinusdreef 2 .
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
Inclusion criteria in this study are:
• Infants born at a gestational age below 30 weeks in a participating centre.
• Parental consent.
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
• Significant congenital malformations.
• Signs of acute placental abruption.
• Total placenta praevia, anterior placenta praevia or invasive placentation
(accreta/percreta).
• Birth by emergency caesarean section (ordered to be executed within 15
minutes).
• 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.
Design
Recruitment
Medical products/devices used
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
metc-ldd@lumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03808051 |
| CCMO | NL67770.058.18 |