Oxygen Saturation Levels for Premature Infants

(OptiSTART Trial)

Overseen By Shelby Unger, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the optimal oxygen saturation levels for premature babies to enhance survival without long-term health issues. Researchers aim to determine if targeting higher oxygen levels (Sat75) is more beneficial than the current standard levels (Sat50). The study will compare these two oxygen goals to assess which leads to better outcomes, such as fewer lung problems and healthier development by age two. This trial is suitable for newborns with a gestational age between 22 and 30 weeks. As an unphased trial, it provides a unique opportunity to contribute to vital research that could improve care for future premature 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.

What prior data suggests that these oxygen saturation targets are safe for premature infants?

Research shows that adjusting oxygen levels for premature babies can affect their health. One study found that babies receiving higher oxygen levels had a slightly lower risk of necrotizing enterocolitis, a serious gut disease, compared to those with lower levels. This suggests that higher oxygen levels might be safer in some cases. However, the optimal level for overall survival and avoiding long-term problems remains unclear.

Oxygen is essential for premature babies but must be used carefully to prevent issues like lung disease. The study under consideration will help determine the safest oxygen levels for these vulnerable babies. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores two innovative approaches to managing oxygen levels in premature infants. Unlike traditional methods that aim for average oxygen saturation levels, the Sat75 protocol targets a higher oxygen saturation, aiming for the 75th percentile observed in healthy newborns, potentially offering better outcomes for these vulnerable babies. Meanwhile, the Sat50 protocol aligns closer to current recommendations but adjusts the oxygen more frequently, which may provide insights into optimizing the balance between oxygen delivery and safety. This trial could reshape how we understand and manage oxygen needs in premature infants, potentially leading to improved health outcomes.

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

Research has shown that using higher oxygen levels, like those targeted in the Sat75 arm of this trial, could benefit preterm infants. Studies have found that these infants often have lower oxygen levels than recommended, suggesting current targets might be too low. Evidence indicates that infants with lower oxygen levels experienced higher death rates and more complications. By aiming for higher oxygen levels, as in the Sat75 arm, the risk of bronchopulmonary dysplasia might decrease, and survival rates could improve without causing long-term health issues. Reviews support this approach, favoring more oxygen for extremely preterm infants. Overall, targeting higher oxygen levels, as in the Sat75 arm, could significantly enhance the health of preterm infants. ^{1 4 5 6 7}

Who Is on the Research Team?

Vishal Kapadia, MD

Principal Investigator

University of Texas Southwestern Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

North Central Baptist Hospital

Collaborator

Sharp Mary Birch Hospital for Women & Newborns

Collaborator

Trials

13

Recruited

6,600+

The Woman's Hospital of Texas

Collaborator

Trials

2

Recruited

1,600+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

University of Florida Health

Collaborator

Trials

10

Recruited

4,200+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

University of Utah

Collaborator

Trials

1,169

Recruited

1,623,000+

Primary Children's Hospital

Collaborator

Trials

22

Recruited

15,900+

Published Research Related to This Trial

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]

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]

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 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 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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05849077

Optimization of Saturation Targets And Resuscitation Trial ... Sat75. 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.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4388792/

Oxygen Saturation Target Range for Extremely Preterm Infants To systematically review evidence evaluating the effect of restricted vs liberal oxygen exposure on morbidity and mortality in extremely preterm infants.

3. brieflands.com brieflands.com/journals/ijp/articles/11650

Percentiles of Oxygen Saturations (SpO2) and Heart Rates ... The target oxygen saturation levels were stated at 2015 world health organization (WHO) recommendations on interventions to improve preterm birth outcomes as ...

4. researchgate.net researchgate.net/publication/321195064_Percentiles_of_Oxygen_Saturations_SpO2_and_Heart_Rates_HR_in_Premature_Infants_in_the_Delivery_Room

Percentiles of Oxygen Saturations (SpO2) and Heart Rates ... Conclusions: Oxygen saturation levels of preterm infants in delivery room are lower than reported in NRP guidelines. Clinicians who use pulse ...

5. masimofoundation.com masimofoundation.com/siteassets/us/documents/pdf/clinical-evidence/set/askie-et-al-jama-2018_set.pdf

Association Between Oxygen Saturation Targeting and ... Other secondary outcome results appear in Figure 3. These results show infants in the lower target group had an increase in death at other time points ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2891970/

Target Ranges of Oxygen Saturation in Extremely Preterm ... A lower target range of oxygenation (85 to 89%), as compared with a higher range (91 to 95%), did not significantly decrease the composite outcome of severe ...

7. ctv.veeva.com ctv.veeva.com/study/optimization-of-saturation-targets-and-resuscitation-trial-optistart

Optimization of Saturation Targets And Resuscitation Trial ... The investigators will randomize 700 infants, 23 0/7- 30 6/7 weeks' GA, to 75th percentile SpO2 goals (Sat75, Intervention) or 50th percentile ...