Clinical trial NCT03166722: Cerebral Regional Tissue Oxygen Saturation to Guide Oxygen Delivery in Preterm Neonates During Immediate Transition
Official title: Cerebral Regional Tissue Oxygen Saturation to Guide Oxygen Delivery in Preterm Neonates During Immediate Transition After Birth: An Investigator-initiated Randomised Multi-centre Multinational Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Preterm Infant
Brain Injuries
Birth Hypoxia
Lead sponsor: Medical University of Graz
Sponsor class: OTHER
Collaborators: name: Royal Alexandra Hospital
First posted: 2017-05-25
Enrollment: 655
Sex: ALL
Minimum age (years): 1
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: investigator-initiated randomised multi-centre multinational clinical trial
Primary purpose: DIAGNOSTIC

Brief summary: The aim of the COSGOD Phase III trial is to examine, if it is possible to increase survival without cerebral injury in preterm neonates \<32 weeks of gestation by monitoring the cerebral tissue oxygen saturation in addition to routine monitoring of arterial oxygen saturation and heart rate and specified clinical treatment guidelines during immediate transition period after birth (the first 15 minutes).

Detailed description: Background

The transition to life after birth is a complex physiological process where the neonate has to establish sufficient ventilation and changes from intra-uterine circulation to extra-uterine circulation take place. During these processes the neonate has to provide the brain with adequate perfusion and oxygen delivery to maintain normal cerebral tissue oxygenation and activity. If hypoxia and bradycardia both common events during immediate transition in preterm neonates occur, cerebral hypoxia-ischaemia may cause perinatal brain injury that is the major causes of mortality and long term neurodevelopmental impairment.

Objectives

The primary objective of the COSGOD Phase III trial is to examine, if it is possible to increase survival without cerebral injury in preterm neonates \<32 weeks of gestation by monitoring the cerebral tissue oxygen saturation in addition to routine monitoring of arterial oxygen saturation (SpO2) and heart rate (HR) and specified clinical treatment guidelines during immediate transition period after birth (the first 15 minutes).

Hypothesis

The investigators hypothesise that using cerebral tissue oxygen saturation in addition to SpO2 and HR monitoring and specified treatment guidelines during immediate transition and resuscitation would increase survival without cerebral injury in preterm neonates.

Trial design

An investigator-initiated randomised, multi-centre, multinational, phase III clinical trial involving preterm infants from European countries and North America.

Inclusion and exclusion criteria

The inclusion criteria are: neonates born more than 8 weeks preterm (gestational age up to 31 weeks and 6 days); decision to conduct full life support; parental informed consent; and cerebral NIRS oximeter placed within three minutes after birth.

Sample size

According to actual data of two European centres (Graz and Rotterdam) and one Canadian centre (Edmonton) the percentage of neonates not affected by mortality and cerebral injury is 65%. Assuming an increase of not affected neonates from 65% to 75% and a dropout rate of 10% a total of 724 neonates are required to detect this difference with a two group χ² test (alpha: 0.05, power: 80%).

Intervention

The premature infants will be randomised into experimental or control group. Both groups will have a near infrared spectroscopy (NIRS) device (left frontal), pulse-oximeter (right wrist) and electrocardiogram placed within three minutes after birth. In the study group, the cerebral tissue saturation, SpO2 and HR readings are visible, and the infant will be treated accordingly using a defined treatment guideline. In the control group, only SpO2 and HR will be visible, and the infant will be treated according routine treatment.

Duration of intervention Monitoring will be started within 3 minutes after birth and the intervention will last during immediate transition period and resuscitation up to 15 minutes after birth.

Follow up

Thereafter, each neonate will be followed up for primary outcome to term date or discharge.

Outcome measures

The primary outcome is mortality and/or cerebral injury defined as any intraventricular bleeding and/or cystic periventricular leucomalacia.

The secondary outcomes are neonatal morbidities.

Eligibility criteria: Inclusion Criteria:

* Preterm neonates less than completed 32 weeks,
* Decision to conduct full life support,
* Written informed consent.

Exclusion Criteria:

* No decision to conduct full life support,
* No written informed consent,
* Congenital malformation.

Primary outcomes:
measure: Mortality and/or occurrence of cerebral injury
timeFrame: up to 19 weeks after birth
Secondary outcomes:
measure: Frequency of neonatal morbidities
timeFrame: up to 19 weeks after birth
measure: Sex
timeFrame: up to 19 weeks after birth
measure: Gestational age
timeFrame: up to 19 weeks after birth
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Department of Pediatrics, Medical University of Graz
state: Styria
city: Innsbruck
country: Austria
facility: Medical University Innsbruck
city: Vienna
country: Austria
facility: Medical University Vienna
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Tübingen
country: Germany
facility: Centre for Pediatric Clinical Studies
city: Cork
country: Ireland
facility: University College Cork
city: Milano
country: Italy
facility: Ospedale dei Bambini "V.Buzzi" Milano
city: Trieste
country: Italy
facility: Institute for Maternal and Child Health, IRCCS Burlo Garofolo
city: Poznań
country: Poland
facility: Poznan University of Medical Sciences
city: Poznań
country: Poland
facility: Uniwersytetu Medycznego im. Karola Marcinkowskiego
city: Ljubljana
country: Slovenia
facility: University Medical Centre Ljubljana
Study officials:
affiliation: Medical University of Graz, Austria
name: Gerhard Pichler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Alexandra Hospital, Edmonton, Canada
name: Georg M Schmölzer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pichler G, Baumgartner S, Biermayr M, Dempsey E, Fuchs H, Goos TG, Lista G, Lorenz L, Karpinski L, Mitra S, Kornhauser-Cerar L, Avian A, Urlesberger B, Schmolzer GM. 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. Trials. 2019 Mar 20;20(1):178. doi: 10.1186/s13063-019-3258-y.