TY - JOUR
T1 - Physiological-based cord clamping in very preterm infants
T2 - the Aeration, Breathing, Clamping 3 (ABC3) trial-statistical analysis plan for a multicenter randomized controlled trial
AU - Willemsen, Sten P.
AU - Knol, Ronny
AU - Brouwer, Emma
AU - van den Akker, Thomas
AU - DeKoninck, Philip L.J.
AU - Lopriore, Enrico
AU - Onland, Wes
AU - de Boode, Willem P.
AU - van Kaam, Anton H.
AU - Nuytemans, Debbie H.
AU - Reiss, Irwin K.M.
AU - Hutten, G. Jeroen
AU - Prins, Sandra A.
AU - Mulder, Estelle E.M.
AU - Hulzebos, Christian V.
AU - van Sambeeck, Sam J.
AU - van der Putten, Mayke E.
AU - Zonnenberg, Inge A.
AU - Te Pas, Arjan B.
AU - Vermeulen, Marijn J.
N1 - Funding Information:
The trial is funded by The Netherlands Organisation for Health Research and Development (project number 852001902). AtP is a recipient of an NWO innovational research incentives scheme (VIDI 91716428). RK received a grant from the Sophia Children’s Hospital Foundation (Rotterdam, S17-14). This project was sponsored by the Gisela Thier Fund (Leiden).
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/3/4
Y1 - 2024/3/4
N2 - BACKGROUND: Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. METHODS: The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. DISCUSSION: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. TRIAL REGISTRATION: ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.
AB - BACKGROUND: Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. METHODS: The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. DISCUSSION: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. TRIAL REGISTRATION: ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.
KW - Cord clamping
KW - Physiological-based cord clamping
KW - Preterm infants
KW - Randomized clinical trial
KW - Statistical Analysis Plan
U2 - 10.1186/s13063-024-08014-y
DO - 10.1186/s13063-024-08014-y
M3 - Article
SN - 1745-6215
VL - 25
JO - Trials
JF - Trials
IS - 1
M1 - 164
ER -