Canadian Oxygen Trial (COT)

Study Overview
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Brief Summary
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Study Question: In infants who are born at gestational ages of 23 0/7 to 27 6/7 weeks, does lowering the concentration of supplemental oxygen to target an arterial oxygen saturation by pulse oximetry (SpO2)of 85-89% compared with 91-95%, from the day of birth until the baby's first discharge home, increase the probability of survival without severe neurosensory disability to a corrected age of 18 months?

Detailed Description
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Most extremely preterm babies require supplemental oxygen for several weeks or even months after birth. The goal of oxygen therapy is to achieve adequate oxygen delivery to the tissues without causing oxygen toxicity and oxidative stress. At present, this goal is elusive in very immature infants. Although it is standard practice in modern neonatal intensive care units to monitor arterial oxygen saturations via pulse oximetry, there is insufficient evidence to guide the choice of the upper and lower alarm limits. A rigorous trial with long-term follow up is urgently needed and long overdue to determine whether oxygen exposure can be reduced safely in extremely preterm infants without increasing the risk of hypoxic death or disability.

Official Title
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Efficacy and Safety of Targeting Lower Arterial Oxygen Saturations to Reduce Oxygen Toxicity and Oxidative Stress in Very Preterm Infants: The Canadian Oxygen Trial (COT)

Conditions
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Respiratory Insufficiency of Prematurity

Intervention / Treatment
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* Other: Titration of oxygen therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Gestational age 23 0/7 - 27 6/7 weeks Postnatal age < 24 hours Exclusion Criteria: Infant not considered viable (decision made not to administer effective therapies) Dysmorphic features or congenital malformations that adversely affect life expectancy or neurodevelopment Known or strongly suspected cyanotic heart disease Persistent pulmonary hypertension, e.g. associated with pulmonary hypoplasia Unlikely to be available for long-term follow-up

Ages Eligible for Study
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Maximum Age: 24 Hours

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Supplemental oxygen to maintain functional arterial oxygen saturations in the range of 85-89%. Dose of oxygen is determined by the individual infant's need to achieve the target oxygen saturations. | Other: Titration of oxygen therapy<br>* Supplemental oxygen to maintain functional arterial oxygen saturations in one of two saturation target ranges.<br>* Other names: Masimo Radical Pulse Oximeter;|
| Active Comparator: 2<br>Supplemental oxygen to maintain functional arterial oxygen saturations in the range of 91-95%. Dose of oxygen is determined by the individual infant's need to achieve the target oxygen saturations. | Other: Titration of oxygen therapy<br>* Supplemental oxygen to maintain functional arterial oxygen saturations in one of two saturation target ranges.<br>* Other names: Masimo Radical Pulse Oximeter;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival without severe neurosensory disability to 18 to 21 months (corrected for prematurity) |  | 18-21 months corrected for prematurity | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retinopathy of prematurity |  | 32 to 44 weeks postmenstrual age | 
| Bronchopulmonary dysplasia |  | 36 weeks postmenstrual age | 
| Brain injury |  | from week one of life up to 36 weeks postmenstrual age | 
| Patent ductus arteriosus |  | until first discharge home | 
| Necrotizing enterocolitis |  | until first discharge home | 
| Growth |  | until 18-21 months corrected for prematurity | 
| respiratory morbidity |  | until 18-21 months corrected for prematurity | 
| Mean developmental index scores on the Bayley Scales |  | 18-21 months corrected for prematurity | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oxygen therapy, neurodevelopmental impairment