Oxygen Saturation Levels for Premature Infants

(OptiSTART Trial)

Overseen By Jennifer Davis, RN

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Disqualifiers: Cyanotic heart disease, Diaphragmatic hernia, others

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

Compensation: Varies

Number of Visits: 36

Duration: First 30 minutes after birth

700 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is designed to answer one of the fundamental gaps in knowledge in the resuscitation of preterm infants at birth: What is the optimal target oxygen saturation (SpO2) range that increases survival without long-term morbidities? Oxygen (O2) is routinely used for the stabilization of preterm infants in the delivery room (DR), but its use is linked with mortality and several morbidities including bronchopulmonary dysplasia (BPD). To balance the need to give sufficient O2 to correct hypoxia and avoid excess O2, the neonatal resuscitation program (NRP) recommends initiating preterm resuscitation with low (≤ 30%) inspired O2 concentration (FiO2) and subsequent titration to achieve a specified target SpO2 range. These SpO2 targets are based on approximated 50th percentile SpO2 (Sat50) observed in healthy term infants. However, the optimal SpO2 targets remain undefined in the preterm infants. Recent data suggest that the current SpO2 targets (Sat50) may be too low. The investigators plan to conduct a multicenter RCT of Sat75 versus Sat50 powered for survival without BPD. The investigators will randomize 700 infants, 23 0/7- 30 6/7 weeks' GA, to 75th percentile SpO2 goals (Sat75, Intervention) or 50th percentile SpO2 goals (Sat50, control). Except for the SpO2 targets, all resuscitations will follow NRP guidelines including an initial FiO2 of 0.3. In Aim 1, the investigators will determine whether targeting Sat75 compared to Sat50 increases survival without lung disease (BPD). In addition, the investigators will compare the rates of other major morbidities such as IVH. In Aim 2, the investigators will determine whether targeting Sat75 compared to Sat50 increases survival without neurodevelopmental impairment at 2 years of age. In Aim 3, the investigators will determine whether targeting Sat75 compared to Sat50 decreases oxidative stress.

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 Sat50 and Sat75 for premature infants?

Research shows that higher oxygen saturation targets (91-95%) in premature infants are linked to improved survival rates compared to lower targets (85-89%). This suggests that aiming for higher oxygen levels, like those in the Sat75 treatment, may be more beneficial for survival. ^{1 2 3 4 5}

Is it safe to use specific oxygen saturation targets in premature infants?

Research shows that targeting lower oxygen saturation levels (85% to 89%) in premature infants can increase the risk of death compared to higher levels (91% to 95%). It's important to monitor and adjust oxygen levels carefully to avoid harm, as both too little and too much oxygen can be dangerous. ^{2 6 7 8 9}

How does the Sat75 treatment differ from other treatments for oxygen saturation in premature infants?

The Sat75 treatment targets a specific oxygen saturation level at the 75th percentile, which is a novel approach compared to the traditional practice of targeting a broader range of oxygen saturation levels. This treatment aims to balance the risks of too much or too little oxygen, which can lead to complications like retinopathy of prematurity or cerebral palsy, by providing a more precise target for oxygen levels in premature infants. ^{2 6 9 10 11}

Research Team

Vishal Kapadia, MD

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

The OptiSTART trial is for premature infants born between 22-30 weeks of gestation. It's not suitable for those with certain heart diseases, if oxygen saturation can't be measured within 3 minutes after birth, or if parents do not wish resuscitation.

Inclusion Criteria

My baby was born between 22 and 30 weeks of pregnancy.

Exclusion Criteria

My unborn baby has been diagnosed with a heart condition that decreases oxygen in the blood.

If the oxygen levels in the baby's blood cannot be measured within 3 minutes of putting the pulse oximeter sensor on the baby.

My parents have decided against resuscitation measures for me.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either Sat75 or Sat50 oxygen saturation targets during delivery room resuscitation

First 30 minutes after birth

In-person during delivery

Follow-up

Participants are monitored for survival without bronchopulmonary dysplasia (BPD) and other morbidities

36 weeks Postmenstrual Age

Regular follow-up visits until 36 weeks PMA

Long-term Follow-up

Neurodevelopmental follow-up to assess survival without neurodevelopmental impairment at 2 years of age

Up to 36 months

Treatment Details

Interventions

• Sat50
• Sat75

Trial Overview This study tests two different oxygen saturation targets during the resuscitation of preterm babies: Sat75 (higher target) and Sat50 (current standard). The goal is to see which leads to better survival rates without lung disease or neurodevelopmental issues by age two.

Participant Groups

Group I: Sat75 Experimental Treatment 1 Intervention

FiO2 will be titrated every 30 seconds by 0.2-0.3 to achieve target SpO2 that approximates the 75th percentile SpO2 observed in healthy term newborns. Percentiles are roughly based on Dawson reference curves of healthy term infants after birth.

Group II: Sat50 Active Control 1 Intervention

FiO2 will be titrated every 30 seconds by 0.1-0.2 to achieve NRP recommended target SpO2 which approximates the 50th percentile SpO2 observed in healthy term newborns. Percentiles are roughly based on Dawson reference curves of healthy term infants after birth.

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

University of Oklahoma

Collaborator

Trials

484

Recruited

95,900+

Findings from Research

A study involving 20 preterm neonates showed that implementing a structured oxygen targeting policy significantly increased the time spent within the desired oxygen saturation range of 88%-95%, from 65.9% to 76.5%.

Using daily feedback through oxygen saturation histograms helped improve compliance with oxygen therapy, suggesting that systematic approaches can enhance the safety and efficacy of oxygen administration in vulnerable neonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Target Oxygen Saturation Among Preterm Neonates on Supplemental Oxygen Therapy: A Quality Improvement Study. Sivanandan, S., Sethi, T., Lodha, R., et al.[2019]

Lower oxygen saturation targets (85% to 89%) in premature infants have been associated with increased mortality compared to higher targets (91% to 95%) in some large international trials.

The upcoming Neonatal Oxygen Prospective Meta-analysis (NeOProM) aims to clarify the risks associated with different oxygen saturation levels, particularly focusing on factors like growth status in small for gestational age infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulse Oximetry Targets in Extremely Premature Infants and Associated Mortality: One-Size May Not Fit All. Raffay, TM., Walsh, MC.[2020]

Higher oxygen saturation (SpO2) targets in preterm infants are linked to an increased risk of severe retinopathy of prematurity, but they also correlate with improved survival rates.

For preterm infants born at less than 28 weeks gestation, it is recommended to maintain oxygen saturation levels at or above 90% based on emerging data from randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retinopathy of prematurity and the oxygen conundrum: lessons learned from recent randomized trials. Fleck, BW., Stenson, BJ.[2013]

A systematic review of 5 trials involving nearly 2896 citations found no significant difference in mortality or neurodevelopmental impairment (NDI) between extremely preterm infants with lower (85%-89%) versus higher (91%-95%) oxygen saturation targets.

However, the lower oxygen target group showed a higher risk of mortality before 18 to 24 months, suggesting that maintaining a higher oxygen saturation target may be safer for these infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen Saturation Targets in Preterm Infants and Outcomes at 18-24 Months: A Systematic Review. Manja, V., Saugstad, OD., Lakshminrusimha, S.[2019]

In a review of five randomized controlled trials involving over 4,800 extremely preterm infants, targeting higher pulse oximeter saturation (SpO2) levels (91-95%) was associated with a significantly lower risk of death compared to lower levels (85-89%).

The lower SpO2 target did not reduce the incidence of bronchopulmonary dysplasia or severe visual impairment, but it increased the risk of serious complications like necrotizing enterocolitis, indicating that maintaining SpO2 levels above 90% is safer for these infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen Saturation Targets for Extremely Preterm Infants after the NeOProM Trials. Stenson, BJ.[2017]

Maintaining oxygen saturation levels between 90% and 93% is recommended for premature infants to balance the risks of both under- and overexposure to supplemental oxygen, which can lead to serious conditions like retinopathy of prematurity and cerebral palsy.

Continuous monitoring and adjustment of supplemental oxygen are crucial, as each healthcare unit should establish its own target ranges and alarm limits based on their specific equipment and patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal oxygen saturation in premature infants. Chang, M.[2021]

In a study of 115 preterm infants, those assigned to a low oxygen saturation target range (85%-89%) experienced a higher incidence of intermittent hypoxemia compared to those in a high target range (91%-95%), particularly before 12 days and after 57 days of life.

The severity and duration of hypoxemia events increased with the infants' postnatal age, indicating that lower oxygen saturation targets may pose risks for preterm infants, warranting further research into the implications of these events on neonatal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia. Di Fiore, JM., Walsh, M., Wrage, L., et al.[2021]

A review of 23 publications from 2011 to 2019 found that targeting oxygen saturation levels of 85% to 89% in infants born before 28 weeks' gestation is associated with increased mortality compared to higher targets of 91% to 95%.

Most commentaries and consensus statements (17 out of 18) recommended maintaining oxygen saturation targets above 89%, highlighting a consensus in the medical community regarding safer practices for these vulnerable infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Recommendations and Practice of Oxygen Therapy in Preterm Infants. Tarnow-Mordi, W., Kirby, A.[2020]

Higher oxygen saturation levels in preterm infants are associated with an increased risk of severe retinopathy of prematurity and pulmonary complications, suggesting that targeting lower saturation levels may not be safe.

Interim results from ongoing trials indicate that targeting oxygen saturation levels below 90% may lead to increased early mortality, highlighting the need for careful management of oxygen levels in these vulnerable infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal oxygen saturations in preterm infants: a moving target. Askie, LM.[2018]

Targeting lower oxygen saturation levels (SpO₂ 85% to 89%) in extremely preterm infants did not significantly affect the overall rates of death or major disability compared to targeting higher levels (SpO₂ 91% to 95%), but it did increase the risk of mortality by 28 per 1000 infants, based on a systematic review of 5 trials involving 4965 infants.

While lower oxygen levels reduced the incidence of retinopathy of prematurity requiring treatment, they also led to a higher incidence of necrotising enterocolitis, indicating a complex trade-off between potential benefits and risks when determining oxygen saturation targets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants. Askie, LM., Darlow, BA., Davis, PG., et al.[2022]

In a study of 150 healthy newborns at an altitude of 1610 m, the mean oxygen saturation was found to be 92% to 93% at 24 to 48 hours of age, providing a reference range for clinical assessments in this population.

As infants aged, oxygen saturation tended to increase during awake states, reaching 93% to 94%, while it remained stable or slightly decreased during sleep, indicating that activity levels can influence oxygen saturation readings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen saturation by pulse oximetry in healthy infants at an altitude of 1610 m (5280 ft). What is normal? Thilo, EH., Park-Moore, B., Berman, ER., et al.[2019]

References

1. India pubmed.ncbi.nlm.nih.gov

Target Oxygen Saturation Among Preterm Neonates on Supplemental Oxygen Therapy: A Quality Improvement Study. [2019]

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

Pulse Oximetry Targets in Extremely Premature Infants and Associated Mortality: One-Size May Not Fit All. [2020]

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

Retinopathy of prematurity and the oxygen conundrum: lessons learned from recent randomized trials. [2013]

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

Oxygen Saturation Targets in Preterm Infants and Outcomes at 18-24 Months: A Systematic Review. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Oxygen Saturation Targets for Extremely Preterm Infants after the NeOProM Trials. [2017]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Optimal oxygen saturation in premature infants. [2021]

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

Low oxygen saturation target range is associated with increased incidence of intermittent hypoxemia. [2021]

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

Current Recommendations and Practice of Oxygen Therapy in Preterm Infants. [2020]

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

Optimal oxygen saturations in preterm infants: a moving target. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Effects of targeting lower versus higher arterial oxygen saturations on death or disability in preterm infants. [2022]

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

Oxygen saturation by pulse oximetry in healthy infants at an altitude of 1610 m (5280 ft). What is normal? [2019]