Oxygen Levels at Birth for Low Birth Weight Infants

(HiLo Trial)

Recruiting at 15 trial locations

Overseen By Barb Kamstra, RN

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Alberta

Disqualifiers: Outborn, Congenital abnormalities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

1200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal oxygen level for helping preterm babies, born before 29 weeks, begin breathing immediately after birth. Preterm babies often have underdeveloped lungs and require special care to prevent brain injuries from improper oxygen levels. The trial compares two groups: one receiving 30% oxygen (low concentration) and the other 60% oxygen (high concentration) to identify which leads to better survival and health outcomes. Eligible babies are those born between 23 and 28 weeks of pregnancy, who will receive full resuscitation and have no major congenital issues. As an unphased trial, this study provides a unique opportunity to contribute to crucial research that could enhance care for future preterm infants.

Will I have to stop taking my current medications?

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

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using higher oxygen levels, such as 60%, for newborns with low birth weight might not be ideal. Some studies have found increased risks, including organ damage and serious brain bleeding, associated with high oxygen use. In certain cases, a nearly fivefold higher risk of death links to higher oxygen levels.

Conversely, starting with lower oxygen levels, like 30%, does not clearly show harm or benefit compared to higher levels. This indicates that experts still lack a definite answer on the best approach.

In summary, while both oxygen levels carry risks and uncertainties, there is insufficient evidence to declare one safer than the other. This trial seeks to determine which level might be better for these tiny, early arrivals. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different oxygen levels at birth might impact low birth weight infants, which could lead to more tailored care strategies. Traditionally, standard care involves using a set oxygen level, but this study tests whether starting with 30% or 60% oxygen and adjusting based on the baby's needs can improve outcomes. By fine-tuning oxygen delivery in the crucial first minutes of life, the trial aims to optimize oxygen saturation levels, potentially reducing complications and improving long-term health for these vulnerable infants.

What evidence suggests that this trial's treatments could be effective for preterm infants?

This trial will compare the effects of different oxygen levels at birth for low birth weight infants. Research has shown that using 60% oxygen, which participants in the 60% group of this trial will receive, does not significantly change survival rates or other health outcomes compared to lower oxygen levels, such as the 30% oxygen that participants in the 30% group will receive. One study found no difference in survival or major health issues when starting with high oxygen (60%) versus low oxygen (30%) at birth. However, higher oxygen levels have been linked to a greater risk of serious brain bleeding, known as intraventricular hemorrhage (IVH), and in some cases, a much higher risk of death. Oxygen is vital for helping these infants breathe, but finding the right balance is crucial to avoid harm. Therefore, determining the best oxygen level is a key focus to improve survival and health for these vulnerable infants. ^{1 2 5 6 7}

Who Is on the Research Team?

Georg Schmolzer

Principal Investigator

University of Alberta

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• 30% oxygen group
• 60% oxygen group

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.

How Is the Trial Designed?

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+

Université de Montréal

Collaborator

Trials

223

Recruited

104,000+

University of Ottawa

Collaborator

Trials

231

Recruited

267,000+

University of British Columbia

Collaborator

Trials

1,506

Recruited

2,528,000+

Memorial University of Newfoundland

Collaborator

Trials

73

Recruited

1,836,000+

University College Cork

Collaborator

Trials

144

Recruited

80,600+

University of Calgary

Collaborator

Trials

827

Recruited

902,000+

Laval University

Collaborator

Trials

439

Recruited

178,000+

Dalhousie University

Collaborator

Trials

177

Recruited

402,000+

University of Toronto

Collaborator

Trials

739

Recruited

1,125,000+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03825835?cond=Hilo&rank=4

NCT03825835 | 30% or 60% Oxygen at Birth to Improve ... Objectives: To determine whether initial resuscitation of preterm neonates with 60 percent versus 30 percent oxygen results in better neurodevelopmental ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10996184/

Does the use of higher versus lower oxygen concentration ... The use of higher versus lower oxygen concentration improve neurodevelopmental outcomes at 18–24 months in very low birthweight infants?

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8958722/

Optimizing oxygen therapy for preterm infants at birth The meta-analysis found no difference in mortality or other clinical outcome when resuscitation was initiated with low oxygen (21–30%) or with high oxygen (60– ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03825835/30-or-60-oxygen-at-birth-to-improve-neurodevelopmental-outcomes-in-very-low-birthweight-infants

30% or 60% Oxygen at Birth to Improve ... This was associated with increased risk of major intraventricular hemorrhage (IVH), and an almost five times higher risk of death in this ...

5. nature.com nature.com/articles/s41371-019-0211-1

Oxygen therapy in premature low birth weight infants is ... Oxygen therapy in premature LBW infants in the neonatal period is associated with higher systolic and diastolic BP levels but has no significant ...

6. publications.aap.org publications.aap.org/pediatrics/article/138/2/e20161576/52503/Oxygen-Targeting-in-Extremely-Low-Birth-Weight

Oxygen Targeting in Extremely Low Birth Weight Infants There was no difference in the primary composite outcome (51.6% in the lower vs 49.7% in the higher saturation range). Mortality was 16.6% in ...

7. mdpi.com mdpi.com/2227-9067/8/11/942

Higher versus Lower Oxygen Concentration during ... There is a lack of evidence for either overall benefit or harm in starting resuscitation with either lower (<30%) or higher (>65%) oxygen for ...