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

• ClinicalTrials.gov Identifier: NCT03166722
• Recruitment Status: Completed
• First Posted: May 25, 2017
• Last Update Posted: February 11, 2022
• Sponsor: Medical University of Graz
• Collaborator: Royal Alexandra Hospital
• Information provided by (Responsible Party): Medical University of Graz

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Preterm Infant; Brain Injuries; Birth Hypoxia	Other: Control group; Device: Study group	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 655 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: investigator-initiated randomised multi-centre multinational clinical trial
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Diagnostic
• 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
• Actual Study Start Date: September 20, 2017
• Actual Primary Completion Date: January 31, 2022
• Actual Study Completion Date: February 10, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Mortality and/or occurrence of cerebral injury [ Time Frame: up to 19 weeks after birth ]
   Number of patients, who die or have intraventricular hemorrhage or have periventricular leucomalacia

Secondary Outcome Measures :

1. Frequency of neonatal morbidities [ Time Frame: up to 19 weeks after birth ]
   Number of patients, who have infection and/or sepsis and/or necrotizing enterocolitis bronchoplumonary dysplasia, retinopathia prematurorumand/or bronchoplumonary dysplasia and /or retinopathia prematurorum
2. Sex [ Time Frame: up to 19 weeks after birth ]
   Number of male and female patients, who die or have intraventricular hemorrhage or have periventricular leucomalacia
3. Gestational age [ Time Frame: up to 19 weeks after birth ]
   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

Eligibility Criteria

• Ages Eligible for Study: 1 Minute to 15 Minutes (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

Austria

Department of Pediatrics, Medical University of Graz

Graz, Styria, Austria, 8036

Medical University Innsbruck

Innsbruck, Austria

Medical University Vienna

Vienna, Austria

Canada, Alberta

Royal Alexandra Hospital

Edmonton, Alberta, Canada, T5H 3V9

Germany

Universitätsklinikum Freiburg

Freiburg, Germany

Centre for Pediatric Clinical Studies

Tübingen, Germany

Ireland

University College Cork

Cork, Ireland

Italy

Ospedale dei Bambini "V.Buzzi" Milano

Milano, Italy

Institute for Maternal and Child Health, IRCCS Burlo Garofolo

Trieste, Italy

Poland

Poznan University of Medical Sciences

Poznań, Poland

Uniwersytetu Medycznego im. Karola Marcinkowskiego

Poznań, Poland

Slovenia

University Medical Centre Ljubljana

Ljubljana, Slovenia

Sponsors and Collaborators

Medical University of Graz

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Medical University of Graz
• ClinicalTrials.gov Identifier: NCT03166722
• Other Study ID Numbers: COSGOD Phase III
• First Posted: May 25, 2017
• Last Update Posted: February 11, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)
• Time Frame: After publication of primary and secondary outcome
• Access Criteria: On demand

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Brain Injuries; Premature Birth; Hypoxia; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Signs and Symptoms, Respiratory