Clinical trial NCT00637169: Canadian Oxygen Trial (COT)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Respiratory Insufficiency of Prematurity
Keywords: oxygen therapy
neurodevelopmental impairment
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2008-03-17
Enrollment: 1201
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Survival without severe neurosensory disability to 18 to 21 months (corrected for prematurity)
timeFrame: 18-21 months corrected for prematurity
Secondary outcomes:
measure: Retinopathy of prematurity
timeFrame: 32 to 44 weeks postmenstrual age
measure: Bronchopulmonary dysplasia
timeFrame: 36 weeks postmenstrual age
measure: Brain injury
timeFrame: from week one of life up to 36 weeks postmenstrual age
measure: Patent ductus arteriosus
timeFrame: until first discharge home
measure: Necrotizing enterocolitis
timeFrame: until first discharge home
measure: Growth
timeFrame: until 18-21 months corrected for prematurity
measure: respiratory morbidity
timeFrame: until 18-21 months corrected for prematurity
measure: Mean developmental index scores on the Bayley Scales
timeFrame: 18-21 months corrected for prematurity
Other outcomes:
Locations:
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Philadelphia
country: United States
facility: Pennsylvania Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania (HUP)
state: Pennsylvania
city: Buenos Aires
country: Argentina
facility: Hospital Sanatorio de la Trinidad & Buenos Aires NICU Network
city: Calgary
country: Canada
facility: Foothills Hospital
state: Alberta
city: Edmonton
country: Canada
facility: Royal Alexandra Hospital
state: Alberta
city: Vancouver
country: Canada
facility: B.C. Children's Hospital
state: British Columbia
city: Winnipeg
country: Canada
facility: St. Boniface General Hospital
state: Manitoba
city: Winnipeg
country: Canada
facility: Winnipeg Health Sciences Centre
state: Manitoba
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University Medical Centre
state: Ontario
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario and Ottawa General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Montreal
country: Canada
facility: CHU Ste. Justine
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
city: Oulu
country: Finland
facility: Oulu University Central Hospital
city: Tuebingen
country: Germany
facility: University Children's Hospital
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Bnai-Zion Medical Center
city: Kfar-Saba
country: Israel
facility: Meir Medical Center
Study officials:
affiliation: McMaster University
name: Barbara Schmidt, MD
role: STUDY_CHAIR
affiliation: Hamilton Health Sciences/McMaster University
name: Robin Roberts, MMath
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Elizabeth Asztalos, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's & Women's Health Centre of BC
name: Alfonso Solimano, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IWK Health Centre
name: Robin Whyte, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Foothills Hospital
name: Jack Rabi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Children's Hospital Tuebingen
name: Christian Poets, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schmidt B, Whyte RK, Asztalos EV, Moddemann D, Poets C, Rabi Y, Solimano A, Roberts RS; Canadian Oxygen Trial (COT) Group. Effects of targeting higher vs lower arterial oxygen saturations on death or disability in extremely preterm infants: a randomized clinical trial. JAMA. 2013 May 22;309(20):2111-20. doi: 10.1001/jama.2013.5555.
citation: Schmidt B, Roberts RS, Whyte RK, Asztalos EV, Poets C, Rabi Y, Solimano A, Nelson H; Canadian Oxygen Trial Group. Impact of study oximeter masking algorithm on titration of oxygen therapy in the Canadian oxygen trial. J Pediatr. 2014 Oct;165(4):666-71.e2. doi: 10.1016/j.jpeds.2014.05.028. Epub 2014 Jun 25.
citation: Jensen EA, Whyte RK, Schmidt B, Bassler D, Vain NE, Roberts RS; Canadian Oxygen Trial Investigators. Association between Intermittent Hypoxemia and Severe Bronchopulmonary Dysplasia in Preterm Infants. Am J Respir Crit Care Med. 2021 Nov 15;204(10):1192-1199. doi: 10.1164/rccm.202105-1150OC.