Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): an investigator-initiated, randomized, multi-center, multi-national, clinical trial on additional cerebral tissue oxygen saturation monitoring combined with defined treatment guidelines versus standard monitoring and treatment as usual in premature infants during immediate transition: study protocol for a randomized controlled trial

Abstract

Background: Transition immediately after birth is a complex physiological process. The neonate has to establish sufficient ventilation to ensure significant changes from intra-uterine to extra-uterine circulation. If hypoxia or bradycardia or both occur, as commonly happens during immediate transition in preterm neonates, cerebral hypoxia-ischemia may cause perinatal brain injury. The primary objective of the COSGOD phase III trial is to investigate whether it is possible to increase survival without cerebral injury in preterm neonates of less than 32 weeks of gestation by targeting cerebral tissue oxygen saturation (crSO2) using specified clinical treatment guidelines during the immediate transition period after birth (the first 15 min) in addition to the routine monitoring of arterial oxygen saturation (SpO2) and heart rate (HR).

Methods/design: COSGOD III is an investigator-initiated, randomized, multi-center, multi-national, phase III clinical trial. Inclusion criteria are neonates of less than 32 weeks of gestation, decision to provide full life support, and parental informed consent. Exclusion criteria are severe congenital malformations of brain, heart, lung, or prenatal cerebral injury or a combination of these. The premature infants will be randomly assigned to study or control groups. Both groups will have a near-infrared spectroscopy (NIRS) device (left frontal), pulse oximeter (right palm/wrist), and electrocardiogram placed immediately after birth. In the study group, the crSO2, SpO2, and HR readings are visible, and the infant will receive treatment in accordance with defined treatment guidelines. In the control group, only SpO2 and HR will be visible, and the infant will receive routine treatment. The intervention period will last for the first 15 min after birth during the immediate transition period and resuscitation. Thereafter, each neonate will be followed up for primary outcome to term date or discharge. The primary outcome is mortality or cerebral injury (or both) defined as any intra-ventricular bleeding or cystic periventricular leukomalacia (or both). Secondary outcomes are neonatal morbidities.

Discussion: crSO2 monitoring during immediate transition has been proven to be feasible and improve cerebral oxygenation during immediate transition. The additional monitoring of crSO2 with dedicated interventions may improve outcome of preterm neonates as evidenced by increased survival without cerebral injury.

Trial registration: ClinicalTrials.gov Identifier: NCT03166722 . Registered March 5, 2017.

Keywords: Cerebral injury; Cerebral oxygenation; Immediate transition; Mortality; Neonate.

Conflict of interest statement

Ethics approval and consent to participate

Medical University of Graz, Austria: Approved 06.06.2016; 28-456 ex15/16

University of Alberta, Edmonton, Canada: Approved 13.07.2016; Pro00065767

Medical University of Vienna, Austria: Approved 17.11.2071; EK Nr: 1823/2017

Medical University of Innsbruck, Austria: Approved 03.10.2017; EK Nr: 1048/2017

University Children’s Hospital of Tübingen, Germany: Approved 27.10.2017; 56/2017BO1

University Medical Centre Ljubljana, Slovenia: Approved 2.11.2017; 0120-529/2017/4

Medical Center-University of Freiburg, Faculty of Medicine, Germany: Approved 18.01.2018; 612/17

Cork University Maternity Hospital, Cork, Ireland: Approved 31.05.2018; ECM 4 17/01/18

Erasmus MC-Sophia Children’s Hospital, Rotterdam, the Netherlands: submitted to ethical committee

Ospedale dei Bambini “Vittore Buzzi” in Milano, Italy: submitted to ethical committee

Poznan University of Medical Sciences, Poznan, Poland: submitted to ethical committee.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Trial flow chart. Abbreviations: ECG electrocardiogram, ITT intention-to-treat, NIRS near-infrared spectroscopy

Fig. 2

Schedule of enrolment, intervention and assessments. Abbreviations: MRI magnetic resonance imaging, NIRS near-infrared spectroscopy

Fig. 3

Intervention - Control group. Abbreviations: CPAP continuous positive airway pressure, FiO2 fraction of inspired oxygen, HR heart rate, IPPV intermittent positive-pressure ventilation, SpO2 arterial oxygen saturation

Fig. 4

Intervention - Study group. Abbreviations: CPAP continuous positive airway pressure, FiO2 fraction of inspired oxygen, HR heart rate, IPPV intermittent positive-pressure ventilation, SpO2 arterial oxygen saturation

Fig. 5

10th and 90th centiles of cerebral tissue oxygen saturation (crSO2) in each minute after birth (according to Table 1 “All neonates” published in Pichler et al. [31])