Respiratory Insufficiency of PrematurityPhase 3COTNCT00637169
Canadian Oxygen Trial (COT)
A Phase 3 study testing Titration of oxygen therapy in people with Respiratory Insufficiency of Prematurity, run by McMaster University at 23 sites in 6 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages Up to 24 hours
- Conditions the study is for
- Respiratory Insufficiency of Prematurity
- What is being tested?
- Titration of oxygen therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,201 participants
- Where
- 23 sitesin 6 countries
- Study dates
- Dec 2006to Dec 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 24 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Gestational age 23 0/7 - 27 6/7 weeks
- Postnatal age < 24 hours
Who cannot join
- 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
Trial locations and contacts
23 sites in 6 countries.
23 sites in 6 countries
Canada14 sites
Foothills Hospital
Calgary, Alberta, T2N 2T9
Royal Alexandra Hospital
Edmonton, Alberta, T5H 3V9
IWK Health Centre
Halifax, Nova Scotia, B3P 1R8
McMaster University Medical Centre
Hamilton, Ontario, L8N 3Z5
Royal Victoria Hospital
Montreal, Quebec, H3A 1A1
CHU Ste. Justine
Montreal, Quebec, H3T 1C5
Children's Hospital of Eastern Ontario and Ottawa General Hospital
Ottawa, Ontario, K1H 8L1
Centre Hospitalier Universitaire de Quebec
Québec, Quebec, G1L 3L5
Royal University Hospital
Saskatoon, Saskatchewan, S7N 0W8
Mount Sinai Hospital
Toronto, Ontario, M5G 1X5
Sunnybrook Health Sciences Centre
Toronto, Ontario, M5S 1B2
B.C. Children's Hospital
Vancouver, British Columbia, V6H 3V4
St. Boniface General Hospital
Winnipeg, Manitoba, R3E 0L8
Winnipeg Health Sciences Centre
Winnipeg, Manitoba, R3L 0L8
United States3 sites
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19035
Hospital of the University of Pennsylvania (HUP)
Philadelphia, Pennsylvania, 19104
Stony Brook University Medical Center
Stony Brook, New York, 11794-8111
Israel3 sites
Soroka University Medical Center
Beersheba, 84101
Bnai-Zion Medical Center
Haifa, 31048
Meir Medical Center
Kfar Saba, 44281
Argentina1 site
Hospital Sanatorio de la Trinidad & Buenos Aires NICU Network
Buenos Aires
About this study
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 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?
Read the 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.
- Conditions
- Respiratory Insufficiency of Prematurity
- Being tested
- Titration of oxygen therapy
- Keywords
- oxygen therapy, neurodevelopmental impairment
- Medical subject headings
- Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Titration of oxygen therapyOther
Also called Masimo Radical Pulse Oximeter
Supplemental oxygen to maintain functional arterial oxygen saturations in one of two saturation target ranges.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | 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. Receives: Other: Titration of oxygen therapy |
| 2 | Active comparator | 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. Receives: Other: Titration of oxygen therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival without severe neurosensory disability to 18 to 21 months (corrected for prematurity)
Measured: 18-21 months corrected for prematurity
Secondary outcomes (8)
Retinopathy of prematurity
Measured: 32 to 44 weeks postmenstrual age
Bronchopulmonary dysplasia
Measured: 36 weeks postmenstrual age
Brain injury
Measured: from week one of life up to 36 weeks postmenstrual age
Patent ductus arteriosus
Measured: until first discharge home
Necrotizing enterocolitis
Measured: until first discharge home
Growth
Measured: until 18-21 months corrected for prematurity
respiratory morbidity
Measured: until 18-21 months corrected for prematurity
Mean developmental index scores on the Bayley Scales
Measured: 18-21 months corrected for prematurity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2008 (estimated)
- Study startDec 2006
- Primary completionSep 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Respiratory Insufficiency of PrematurityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,201 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Barbara Schmidt, MD, Study chair, McMaster UniversityRobin Roberts, MMath, Principal investigator, Hamilton Health Sciences/McMaster UniversityElizabeth Asztalos, MD, Principal investigator, Sunnybrook Health Sciences CentreAlfonso Solimano, MD, Principal investigator, Children's & Women's Health Centre of BCRobin Whyte, MD, Principal investigator, IWK Health CentreJack Rabi, MD, Principal investigator, Foothills HospitalChristian Poets, MD, Principal investigator, University Children's Hospital Tuebingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00637169
- Sponsor's protocol ID
- NTG-2006-COT
- Other IDs
- MCT-79217/ISRCTN62491227
- Acronym
- COT
- Status last verified
- Dec 2014
- First submitted
- 6 Mar 2008
- Last updated
- 22 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 23644995Schmidt 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.
PubMed 24973289Jensen 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.
PubMed 34428130
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00637169
- Acronym / sponsor ID
- COT / NTG-2006-COT
- Conditions
- Respiratory Insufficiency of Prematurity
- Keywords
- oxygen therapy, neurodevelopmental impairment
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,201 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Dec 2006
- Primary completion
- Sep 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 17 Mar 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Other: Titration of oxygen therapySupplemental 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. |
| 2 | Active comparator | Other: Titration of oxygen therapySupplemental 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. |
Who may qualify
- Ages
- Up to 24 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- Gestational age 23 0/7 - 27 6/7 weeks
- Postnatal age < 24 hours
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Titration of oxygen therapyAlso: Masimo Radical Pulse OximeterSupplemental oxygen to maintain functional arterial oxygen saturations in one of two saturation target ranges. | Other | 1, 2 |
Primary outcome
Survival without severe neurosensory disability to 18 to 21 months (corrected for prematurity)
Time frame: 18-21 months corrected for prematurity
8 secondary outcomes
Retinopathy of prematurity
Time frame: 32 to 44 weeks postmenstrual age
Bronchopulmonary dysplasia
Time frame: 36 weeks postmenstrual age
Brain injury
Time frame: from week one of life up to 36 weeks postmenstrual age
Patent ductus arteriosus
Time frame: until first discharge home
Necrotizing enterocolitis
Time frame: until first discharge home
Growth
Time frame: until 18-21 months corrected for prematurity
respiratory morbidity
Time frame: until 18-21 months corrected for prematurity
Mean developmental index scores on the Bayley Scales
Time frame: 18-21 months corrected for prematurity
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2018.
- Results publication: PubMed 23644995Schmidt 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.
- Results publication: PubMed 24973289Schmidt 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.
- Derived from this study: PubMed 34428130Jensen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Barbara Schmidt, MD study chair
McMaster University
Robin Roberts, MMath principal investigator
Hamilton Health Sciences/McMaster University
Elizabeth Asztalos, MD principal investigator
Sunnybrook Health Sciences Centre
23 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Titration of oxygen therapy in people with Respiratory Insufficiency of Prematurity, run by McMaster University at 23 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Canada, United States, Israel, Argentina, Finland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival without severe neurosensory disability to 18 to 21 months (corrected for prematurity) (time frame: 18-21 months corrected for prematurity). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00637169, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2018.