Cerebral Regional Tissue Oxygen Saturation to Guide Oxygen Delivery in Preterm Neonates During Immediate Transition (COSGOD)

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

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).

Study Overview

• Status: Completed
• Conditions: Brain Injuries; Preterm Infant; Birth Hypoxia
• Intervention / Treatment: Device: Study group; Other: Control group

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.

• Study Type: Interventional
• Enrollment (Actual): 655
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria
    • Medical University Innsbruck
  • Vienna, Austria
    • Medical University Vienna
  • Styria
    • Graz, Styria, Austria, 8036
      • Department of Pediatrics, Medical University of Graz
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5H 3V9
      • Royal Alexandra Hospital
• Germany
  • Freiburg, Germany
    • Universitätsklinikum Freiburg
  • Tübingen, Germany
    • Centre for Pediatric Clinical Studies
• Ireland
  • Cork, Ireland
    • University College Cork
• Italy
  • Milano, Italy
    • Ospedale dei Bambini "V.Buzzi" Milano
  • Trieste, Italy
    • Institute for Maternal and Child Health, IRCCS Burlo Garofolo
• Poland
  • Poznań, Poland
    • Poznan University of Medical Sciences
  • Poznań, Poland
    • Uniwersytetu Medycznego im. Karola Marcinkowskiego
• Slovenia
  • Ljubljana, Slovenia
    • University Medical Centre Ljubljana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study group: Invos 5100; Supplemental oxygen support and respiratory/circulatory support is guided by cerebral regional tissue oxygenation (crSO2) measured with near-infrared spectroscopy ("INVOS 5100" ), in addition to the SpO2/HR (oxygen saturation/heart rate) monitoring according to routine.	Device: Study group; Cerebral NIRS measurement with INVOS 5100 during immediate transition in addition to SpO2 and HR monitoring
Active Comparator: Control group: Routine care; Supplemental oxygen support and respiratory/circulatory support is guided by SpO2/HR monitoring according to routine - The resuscitation team is blinded to the crSO2 monitoring.	Other: Control group; SpO2 and HR monitoring and routine treatment during immediate transition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality and/or occurrence of cerebral injury	Number of patients, who die or have intraventricular hemorrhage or have periventricular leucomalacia	up to 19 weeks after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of neonatal morbidities	Number of patients, who have infection and/or sepsis and/or necrotizing enterocolitis bronchoplumonary dysplasia, retinopathia prematurorumand/or bronchoplumonary dysplasia and /or retinopathia prematurorum	up to 19 weeks after birth
Sex	Number of male and female patients, who die or have intraventricular hemorrhage or have periventricular leucomalacia	up to 19 weeks after birth
Gestational age	Number of patients with less than 28 weeks of gestation and more than or equal 28 weeks of gestation, who die or have intraventricular hemorrhage or have periventricular leucomalacia	up to 19 weeks after birth

Collaborators and Investigators

• Sponsor: Medical University of Graz
• Collaborators: Royal Alexandra Hospital
• Investigators: Principal Investigator: Gerhard Pichler, MD, Medical University of Graz, Austria; Principal Investigator: Georg M Schmölzer, MD, PhD, Royal Alexandra Hospital, Edmonton, Canada

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Actual): January 31, 2022
• Study Completion (Actual): February 10, 2022

Study Registration Dates

• First Submitted: May 3, 2017
• First Submitted That Met QC Criteria: May 24, 2017
• First Posted (Actual): May 25, 2017

Study Record Updates

• Last Update Posted (Actual): February 11, 2022
• Last Update Submitted That Met QC Criteria: February 10, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Signs and Symptoms, Respiratory; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Brain Injuries; Premature Birth; Hypoxia
• Other Study ID Numbers: COSGOD Phase III

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The demographic data and data of primary and secondary outcome will be stored at and available form the Institut for Medical Informatics, Statistics und Documentation, Medical University of Graz, Austria
• IPD Sharing Time Frame: After publication of primary and secondary outcome
• IPD Sharing Access Criteria: On demand
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No