Oxygen Levels at Birth for Low Birth Weight Infants

(HiLo Trial)

Recruiting in Palo Alto (17 mi)

+18 other locations

Overseen by Georg Schmolzer

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: University of Alberta

Disqualifiers: Outborn, Congenital abnormalities, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Preterm birth, or birth before 37 weeks' gestation, is increasingly common, occurring in 8 percent of pregnancies in Canada. Preterm birth is associated with many health complications, particularly when the birth happens before 29 weeks' gestation. At this gestational age, the lungs are not fully developed and it is not uncommon for infants to have problems breathing at the time of birth. One complication that can arise is when an infant stops breathing and needs to be resuscitated. When preterm babies need to be resuscitated doctors must take special care because of the small infant size and the immaturity of the brain and lungs. Oxygen is used to resuscitate babies who need it, but unfortunately there is disagreement about the best oxygen concentration to use. Oxygen concentration is important because both too much and too little oxygen can cause brain injury. This research aims to fill this knowledge gap by participating in an international clinical trial to compare the effects of resuscitating babies less than 29 weeks' gestational age with either a low oxygen concentration or a high oxygen concentration. The oxygen concentrations have been selected using the best available knowledge. This will be a cluster randomized trial where each participating hospital will be randomized to either 30 or 60 percent oxygen for the recruitment of 30 infants, and afterwards randomized to the other group for the recruitment of another 30 infants. After the trial, the investigator will determine whether the babies resuscitated with low oxygen or those resuscitated with high oxygen have better survival and long-term health outcomes. This research fills a critical knowledge gap in the care of extremely preterm babies and will impact their survival both here in Canada and internationally.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications.

What data supports the effectiveness of the treatment for low birth weight infants?

Research suggests that using a lower oxygen concentration, like 30% FiO2, during resuscitation of preterm infants may result in less oxidative stress and better outcomes compared to higher oxygen levels. Additionally, adaptive control of oxygen delivery has been shown to maintain stable oxygen levels in neonates more effectively than standard methods. ^{1 2 3 4 5}

Is oxygen therapy safe for low birth weight infants?

Recent studies suggest that high oxygen levels at birth can be more harmful than previously thought for extremely low birth weight infants. It's important to use the lowest effective oxygen concentration to avoid potential toxicity. ^{4 6 7 8 9}

How does the oxygen level treatment for low birth weight infants differ from other treatments?

This treatment is unique because it uses specific oxygen concentrations (30% or 60%) to manage oxygen levels in low birth weight infants, aiming to reduce the risk of oxygen toxicity compared to higher oxygen levels traditionally used. Recent research suggests that lower oxygen levels can be safer and more effective for these infants, as high oxygen concentrations can be harmful. ^{3 4 5 6 10}

Research Team

Georg Schmolzer

Principal Investigator

University of Alberta

Eligibility Criteria

This trial is for very low birthweight infants born between 23 and nearly 29 weeks of gestation, who will receive full resuscitation at the study center without major congenital abnormalities. It excludes those not born in this range, with significant birth defects, or who won't get full resuscitation.

Inclusion Criteria

My baby was born between 23 and 29 weeks without major birth defects and received full resuscitation.

Exclusion Criteria

Babies who were not given their first medical care at the study hospital.

My infant was born with a major birth defect.

My baby was born prematurely.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Resuscitation

Infants are resuscitated with either 30% or 60% oxygen concentration for the first 5 minutes after birth, followed by oxygen titration for stability

10 minutes

In-hospital (immediate post-birth)

Neonatal Intensive Care

Infants are monitored and treated in the Neonatal Intensive Care Unit (NICU) for complications and stabilization

Up to 2-3 months

Follow-up

Participants are monitored for neurodevelopmental outcomes and mortality

24 months

Regular follow-up visits

Treatment Details

Interventions

• 30% oxygen group (Other)
• 60% oxygen group (Other)

Trial Overview The trial compares two oxygen levels used during resuscitation of premature babies: one group receives 30% oxygen and another gets 60%. Hospitals are randomly chosen to use one level for the first set of infants then switch to the other for a new set.

Participant Groups

Group I: 60% group Experimental Treatment 1 Intervention

Infants in the 60% oxygen group will remain in 60% oxygen (O2) until 5 min of age. At 5 min of age, the clinical team will assess oxygen saturation (SpO2). If SpO2 is \<85%, O2 should be increased by 10-20% every 60 sec to achieve SpO2 of 85% or greater or a SpO2 of 90-95% at 10 min of age. If SpO2 are greater than 95% at or before 5 min of age, O2 should be decreased stepwise (every 60 sec) with an aim to maintain SpO2 of 85% or greater during 5-10 min of age or 90-95% at and beyond 10 min of age. Intervention: Infants randomized to the 60% oxygen group will receive 60% oxygen at birth for the first 5 minutes. At 5 minutes oxygen can be adjusted as needed.

Group II: 30% group Active Control 1 Intervention

Infants in the 30% oxygen group will remain in 30% oxygen (O2) until 5 min of age. At 5 min of age, the clinical team will assess oxygen saturation (SpO2). If SpO2 is \<85%, O2 should be increased by 10-20% every 60 sec to achieve SpO2 of 85% or greater or a SpO2 of 90-95% at 10 min of age. If SpO2 are greater than 95% at or before 5 min of age, O2 should be decreased stepwise (every 60 sec) with an aim to maintain SpO2 of 85% or greater during 5-10 min of age or 90-95% at and beyond 10 min of age. Intervention: Infants randomized to the 30% oxygen group will receive 30% oxygen at birth for the first 5 minutes. At 5 minutes oxygen can be adjusted as needed.

30% oxygen group is already approved in Canada for the following indications:

Approved in Canada as 30% oxygen for:

• Resuscitation of preterm infants <29 weeks gestation

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Bill Flanagan

University of Alberta

Chief Executive Officer since 2020

LLB from University of Toronto, LLM from Columbia University

Dr. Verna Yiu

University of Alberta

Chief Medical Officer since 2012

MD from University of Alberta, Fellowship in Pediatric Nephrology at Harvard University

Université de Montréal

Collaborator

Trials

223

Recruited

104,000+

Houda Bahig

Université de Montréal

Chief Medical Officer since 2021

MD from Université de Montréal

Daniel Jutras

Université de Montréal

Chief Executive Officer since 2020

LLB from Université de Montréal, LLM from Harvard University

University of Ottawa

Collaborator

Trials

231

Recruited

267,000+

Dr. Pardeep Nijhawan

University of Ottawa

Chief Medical Officer since 2022

MD from the University of Ottawa

Dr. Erich Mohr

University of Ottawa

Chief Executive Officer since 2015

PhD in Neuropsychology from the University of Victoria

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Dr. Christopher Haqq

University of British Columbia

Chief Medical Officer since 2019

MD, University of British Columbia

Bekki Bracken Brown

University of British Columbia

Chief Executive Officer since 2023

Bachelor's degree from Duke University

Memorial University of Newfoundland

Collaborator

Trials

73

Recruited

1,836,000+

Dr. Jennifer Lokash

Memorial University of Newfoundland

Chief Executive Officer

PhD in English Literature

Dr. Ken Fowler

Memorial University of Newfoundland

Chief Medical Officer since 2023

MD

University College Cork

Collaborator

Trials

144

Recruited

80,600+

Professor John O'Halloran

University College Cork

Chief Executive Officer since 2021

PhD in Zoology from University College Dublin

Professor Helen Whelton

University College Cork

Chief Medical Officer since 2021

BDS, PhD in Dental Science

University of Calgary

Collaborator

Trials

827

Recruited

902,000+

Dr. Shweta Patel

University of Calgary

Chief Medical Officer since 2020

MD from the University of Baroda Medical College, India

Dr. Edward McCauley

University of Calgary

President and Vice-Chancellor since 2018

PhD in Ecology and Evolutionary Biology from the University of California, Santa Barbara

Laval University

Collaborator

Trials

439

Recruited

178,000+

Dr. Pedro O de Campos-Lima

Laval University

Chief Medical Officer since 1998

MD from Federal University of Juiz de Fora, PhD in Tumor Biology from Karolinska Institute

Dr. Manuel Caruso

Laval University

Chief Executive Officer since 1998

PhD in Virology from Pierre and Marie Curie University

Dalhousie University

Collaborator

Trials

177

Recruited

402,000+

Dr. David Berd

Dalhousie University

Chief Medical Officer since 2020

MD

Dr. Kim Brooks

Dalhousie University

Chief Executive Officer since 2023

PhD in Tax Law

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Allison Brown

University of Toronto

Chief Medical Officer

PhD in Chemical Engineering from the University of Toronto

Michael Sefton

University of Toronto

Chief Executive Officer since 2017

PhD in Chemical Engineering from the University of Toronto and MIT

Findings from Research

In a study of 14 premature infants with bronchopulmonary dysplasia, adaptive control of inspired oxygen (FIO2) significantly improved the maintenance of desired arterial hemoglobin saturation (SO2) levels, achieving stable SO2 values 81% of the time compared to 54% with standard protocols.

The adaptive control method not only maintained better oxygen saturation but also reduced fluctuations and overshoots in SO2 levels, indicating it is a more efficient technique for managing oxygen delivery in neonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive control of inspired oxygen delivery to the neonate. Bhutani, VK., Taube, JC., Antunes, MJ., et al.[2019]

In a study of six newborn foals, it was found that their ability to increase arterial oxygen tension (Pao2) improved significantly with age, peaking at seven days old.

Oxygen delivery method (face mask vs. intranasal tube) and duration of administration (up to 20 minutes) had minimal impact on Pao2 levels, with peak values reached within just 2 minutes of inhalation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to oxygen administration in foals: effect of age, duration and method of administration on arterial blood gas values. Stewart, JH., Rose, RJ., Barko, AM.[2019]

In a study involving 193 preterm infants, starting resuscitation with 30% oxygen did not lead to a significant difference in the incidence of bronchopulmonary dysplasia (BPD) compared to starting with 65% oxygen, indicating that both levels are similarly safe.

There were no notable differences in oxidative stress markers between the two groups, suggesting that using 30% oxygen during resuscitation is as effective as 65% in minimizing oxidative stress in preterm infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resuscitation of preterm infants with different inspired oxygen fractions. Rook, D., Schierbeek, H., Vento, M., et al.[2017]

Switching from 100% oxygen to 21% oxygen during newborn resuscitation could potentially save over 100,000 newborn lives each year globally, marking a significant advancement in neonatal care.

For term and late preterm infants, resuscitation should generally begin with 21% oxygen, while extremely low birth weight infants may require an initial oxygen level between 21% and 30%, highlighting the need for tailored approaches based on the infant's condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Why are we still using oxygen to resuscitate term infants? Saugstad, OD.[2013]

In a study of 12 extremely low birth weight infants over 726 hours, caregivers made frequent manual adjustments to the fraction of inspired oxygen (FiO2), with 851 increases and 1309 decreases, indicating a high variability in oxygen management.

Significant FiO2 adjustments were often linked to medical or nursing procedures, highlighting the challenges in maintaining stable oxygen saturation levels and the potential difficulty in automating these adjustments effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An observational study to quantify manual adjustments of the inspired oxygen fraction in extremely low birth weight infants. van der Eijk, AC., Dankelman, J., Schutte, S., et al.[2022]

Resuscitating extremely low birth weight (ELBW) infants with 21% oxygen instead of 100% oxygen can reduce neonatal mortality by 30-40% and lead to quicker recovery times, based on a review of studies involving up to 2,011 newborns.

Maintaining oxygen saturation (SaO2) levels between 85-93% in ELBW infants significantly lowers the risk of retinopathy of prematurity and chronic lung disease, while avoiding fluctuations in SaO2 is crucial for their health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal oxygenation at birth and in the neonatal period. Saugstad, OD.[2007]

Oxygen therapy should start with the minimum effective dose, with initial FiO2 levels ranging from 24% to 100% based on the patient's condition, particularly in cases of COPD exacerbations and chronic hypercapnia.

High FiO2 levels can be safely administered for limited durations, with guidelines suggesting that 100% oxygen is safe for less than six hours, while 70% can be used for up to 24 hours, and 45% should be the upper limit for longer durations to prevent oxygen toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen therapy and oxygen toxicity. Tinits, P.[2022]

In a study involving 45 episodes of moderate to severe asthma, administering 35% oxygen was found to be safe and likely sufficient for oxygenation before measuring arterial blood gases.

Using a lower concentration of oxygen could increase the risk of significant hypoxemia in asthma patients, highlighting the importance of starting with 35% oxygen in acute cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

'Safe oxygen' in acute asthma: prospective trial using 35% Ventimask prior to admission. Ford, DJ., Rothwell, RP.[2019]

In a study of 477 neonates in a Nairobi neonatal unit, 29.2% were found to have hypoxaemia, which is significantly associated with increased mortality, particularly in those showing signs of respiratory distress like nasal flaring and retractions.

Despite receiving oxygen therapy, a large proportion of neonates (64%) had oxygen saturation levels outside the recommended target range at multiple time points, highlighting the need for improved oxygen delivery strategies in low-resource settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulse oximetry values of neonates admitted for care and receiving routine oxygen therapy at a resource-limited hospital in Kenya. Morgan, MC., Maina, B., Waiyego, M., et al.[2021]

Automated adjustment of inspired oxygen fraction (FiO2) significantly improved the time very low birth weight infants spent within the target arterial oxygen saturation (SpO2) range, increasing it from 69.1% to 76.3% compared to manual adjustments.

The use of automated FiO2 control also reduced the number of prolonged hypoxemic episodes (SpO2 <88%) significantly, but it did not have a notable impact on cerebral tissue oxygen saturation (SctO2).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of automated adjustment of the inspired oxygen on fluctuations of arterial and regional cerebral tissue oxygenation in preterm infants with frequent desaturations. Waitz, M., Schmid, MB., Fuchs, H., et al.[2015]

References

1. United States pubmed.ncbi.nlm.nih.gov

Adaptive control of inspired oxygen delivery to the neonate. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Response to oxygen administration in foals: effect of age, duration and method of administration on arterial blood gas values. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Resuscitation of preterm infants with different inspired oxygen fractions. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Why are we still using oxygen to resuscitate term infants? [2013]

5. Norway pubmed.ncbi.nlm.nih.gov

An observational study to quantify manual adjustments of the inspired oxygen fraction in extremely low birth weight infants. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Optimal oxygenation at birth and in the neonatal period. [2007]

7. United States pubmed.ncbi.nlm.nih.gov

Oxygen therapy and oxygen toxicity. [2022]

8. England pubmed.ncbi.nlm.nih.gov

'Safe oxygen' in acute asthma: prospective trial using 35% Ventimask prior to admission. [2019]

9. Australia pubmed.ncbi.nlm.nih.gov

Pulse oximetry values of neonates admitted for care and receiving routine oxygen therapy at a resource-limited hospital in Kenya. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Effects of automated adjustment of the inspired oxygen on fluctuations of arterial and regional cerebral tissue oxygenation in preterm infants with frequent desaturations. [2015]