Multicentre, randomised controlled trial of physiological-based cord clamping versus immediate cord clamping in infants with a congenital diaphragmatic hernia (PinC): statistical analysis plan
Emily J. J. Horn-Oudshoorn,
Marijn J. Vermeulen,
Ronny Knol,
Rebekka Bout-Rebel,
Arjan B. te Pas,
Stuart B. Hooper,
Suzan C. M. Cochius-den Otter,
Rene M. H. Wijnen,
Kelly J. Crossley,
Neysan Rafat,
Thomas Schaible,
Willem P. de Boode,
Anne Debeer,
Berndt Urlesberger,
Calum T. Roberts,
Florian Kipfmueller,
Irma Capolupo,
Carmen M. Burgos,
Bettina E. Hansen,
Irwin K. M. Reiss,
Philip L. J. DeKoninck
Affiliations
Emily J. J. Horn-Oudshoorn
Division of Neonatology, Department of Neonatal and Paediatric Intensive Care, Erasmus MC University Medical Center
Marijn J. Vermeulen
Division of Neonatology, Department of Neonatal and Paediatric Intensive Care, Erasmus MC University Medical Center
Ronny Knol
Division of Neonatology, Department of Neonatal and Paediatric Intensive Care, Erasmus MC University Medical Center
Rebekka Bout-Rebel
Division of Neonatology, Department of Neonatal and Paediatric Intensive Care, Erasmus MC University Medical Center
Arjan B. te Pas
Division of Neonatology, Department of Paediatrics, Leiden University Medical Center
Stuart B. Hooper
The Ritchie Centre, Hudson Institute for Medical Research, Monash University
Suzan C. M. Cochius-den Otter
Division of Paediatric Intensive Care, Department of Neonatal and Paediatric Intensive Care, Erasmus MC University Medical Center
Rene M. H. Wijnen
Division of Paediatric Intensive Care, Department of Neonatal and Paediatric Intensive Care, Erasmus MC University Medical Center
Kelly J. Crossley
The Ritchie Centre, Hudson Institute for Medical Research, Monash University
Neysan Rafat
Department of Neonatology, University Medical Center Mannheim
Thomas Schaible
Department of Neonatology, University Medical Center Mannheim
Willem P. de Boode
Division of Neonatology, Department of Paediatrics, Radboudumc University Medical Center, Radboud Institute for Health Sciences, Amalia Children’s Hospital
Anne Debeer
Department of Neonatology, University Hospitals Leuven
Berndt Urlesberger
Division of Neonatology, Department of Paediatrics and Adolescent Medicine, Medical University of Graz
Calum T. Roberts
Department of Paediatrics, Monash University
Florian Kipfmueller
Department of Neonatology and Paediatric Intensive Care Medicine, University of Bonn Children’s Hospital
Irma Capolupo
Department of Medical and Surgical Neonatology, Bambino Gesu Children’s Hospital, IRCCS
Carmen M. Burgos
Department of Paediatric Surgery, Karolinska University Hospital, Department of Women’s and Children’s Health, Karolinska Institutet
Bettina E. Hansen
Department of Epidemiology, Erasmus MC University Medical Center
Irwin K. M. Reiss
Division of Neonatology, Department of Neonatal and Paediatric Intensive Care, Erasmus MC University Medical Center
Philip L. J. DeKoninck
Division of Neonatology, Department of Neonatal and Paediatric Intensive Care, Erasmus MC University Medical Center
Abstract Background Infants born with congenital diaphragmatic hernia (CDH) are at high risk of respiratory insufficiency and pulmonary hypertension. Routine practice includes immediate clamping of the umbilical cord and endotracheal intubation. Experimental animal studies suggest that clamping the umbilical cord guided by physiological changes and after the lungs have been aerated, named physiological-based cord clamping (PBCC), could enhance the fetal-to-neonatal transition in CDH. We describe the statistical analysis plan for the clinical trial evaluating the effects of PBCC versus immediate cord clamping on pulmonary hypertension in infants with CDH (PinC trial). Design The PinC trial is a multicentre, randomised controlled trial in infants with isolated left-sided CDH, born ≥ 35.0 weeks of gestation. The primary outcome is the incidence of pulmonary hypertension in the first 24 h after birth. Maternal outcomes include estimated maternal blood loss. Neonatal secondary outcomes include mortality before discharge, extracorporeal membrane oxygenation therapy, and number of days of mechanical ventilation. Infants are 1:1 randomised to either PBCC or immediate cord clamping using variable random permutated block sizes (4–8), stratified by treatment centre and estimated severity of pulmonary hypoplasia (i.e. mild/moderate/severe). At least 140 infants are needed to detect a relative reduction in pulmonary hypertension by one third, with 80% power and 0.05 significance level. A chi-square test will be used to evaluate the hypothesis that PBCC decreases the occurrence of pulmonary hypertension. This plan is written and submitted without knowledge of the collected data. The trial has been ethically approved. Trial registration ClinicalTrials.gov NCT04373902 (registered April 2020).
