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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Preterm Infant, Brain Injuries, Birth Hypoxia

Intervention / Treatment
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* Other: Control group
* Device: Study group


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Minute
Maximum Age: 15 Minutes

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: investigator-initiated randomised multi-centre multinational clinical trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group: Invos 5100<br>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<br>* Cerebral NIRS measurement with INVOS 5100 during immediate transition in addition to SpO2 and HR monitoring<br>|
| Active Comparator: Control group: Routine care<br>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<br>* SpO2 and HR monitoring and routine treatment during immediate transition<br>|

What is the study measuring?
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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 |