Cerebral Saturation Monitoring for Brain Hypoxia in Premature Infants

(BOX Trial)

Overseen By Valerie Chock, MD

Age: < 18

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: Congenital conditions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if monitoring and adjusting brain oxygen levels in very premature infants can improve their development by age two. Using near-infrared spectroscopy (NIRS), one group will have their brain oxygen levels actively managed with a clinical algorithm, while the other group will be monitored without adjustments. The researchers aim to see if the managed group shows better developmental outcomes. This trial targets babies born very early, specifically between 23 to 29 weeks of pregnancy and less than 6 hours old. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could enhance care for future premature infants.

Do I need to stop my current medications for this trial?

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

What prior data suggests that this protocol is safe for monitoring cerebral saturation in premature infants?

Research shows that using near-infrared light to check oxygen levels in the brains of premature babies is safe and non-invasive. This method helps estimate how much oxygen the brain receives, which is crucial for brain health. Studies have found that this technology can alert doctors if a baby's brain isn't getting enough oxygen, allowing them to take action to improve the baby's condition.

In this trial, researchers use a special plan to keep brain oxygen levels safe for premature infants. Previous research with similar methods has explored the benefits and any possible risks. This research aims to improve outcomes for preterm infants by ensuring their brains receive the right amount of oxygen.

Overall, using this light technology and guidelines to maintain brain oxygen levels appears well-tolerated, with no significant reports of serious side effects in similar studies. This trial aims to confirm these findings and ensure this approach helps improve early brain development. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the clinical algorithm for monitoring cerebral saturation in premature infants because it introduces a proactive approach to managing brain oxygen levels. Unlike traditional methods that might not intervene until problems are noticeable, this algorithm uses near-infrared spectroscopy (NIRS) to provide real-time data and guide interventions to keep cerebral oxygen saturation within a target range. This could potentially prevent brain hypoxia-related complications early on, offering a more precise and responsive way to support the delicate brains of premature infants during their critical first week of life.

What evidence suggests that this clinical algorithm is effective for improving neurodevelopmental outcomes in premature infants?

Research has shown that monitoring brain oxygen levels in premature babies can lead to better health outcomes. In this trial, participants in the targeted Csats arm will undergo NIRS (near-infrared spectroscopy) monitoring of cerebral saturations (Csat) with algorithm-driven clinical interventions to maintain Csat within a target range during the first week of life. A review of several studies has found that adjusting treatments based on these oxygen levels can improve survival rates in newborns. One study found that a focused approach might reduce serious brain injuries, such as bleeding in the brain and damage to white matter. This method uses NIRS technology to help maintain healthy brain oxygen levels. Overall, early evidence suggests that keeping brain oxygen levels within a certain range may support healthier brain development in very premature babies. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for very preterm infants less than 6 hours old, born at least 23 but less than 29 weeks gestation. It's not suitable for babies with skin issues preventing NIRS sensor placement, life expectancy-affecting congenital conditions other than premature birth, or those not receiving full intensive care.

Inclusion Criteria

I am less than 6 hours old.

My baby was born between 23 and 29 weeks of pregnancy.

Exclusion Criteria

My skin cannot support the placement of NIRS sensors.

You have a condition that you were born with that could affect how long you live or how your brain develops.

I have chosen not to receive all possible intensive care treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Infants are monitored for cerebral saturations using NIRS, with targeted interventions for those in the targeted Csat group during the first week of life

1 week

Continuous monitoring

Follow-up

Participants are monitored for neurodevelopmental outcomes and other health indicators until hospital discharge

3 months

Long-term Follow-up

Neurodevelopmental outcomes assessed using Bayley Scales at 22-26 months of age

22-26 months

What Are the Treatments Tested in This Trial?

Interventions

• Clinical algorithm

Trial Overview The study tests if setting target ranges for brain oxygen levels in extremely preterm infants improves their brain development outcomes by age 22-26 months. Infants are randomly assigned to either a group with visible cerebral oxygen readings or a control group with hidden readings.

How Is the Trial Designed?

Group I: Non-targeted Csats Active Control 1 Intervention

Subjects randomized to the non-targeted Csat arm will have NIRS (near-infrared spectroscopy) monitoring of Csats, but Csat values will be obscured and not available to providers. These subjects will not have any algorithm-driven clinical interventions for Csat.

Group II: Targeted Csats Active Control 1 Intervention

Subjects randomized to the targeted Csat arm will have NIRS monitoring of cerebral saturations (Csat) and will have algorithm-driven clinical interventions to maintain Csat within target range in the first week of life.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Published Research Related to This Trial

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]

Citations

1. link.springer.com link.springer.com/article/10.1007/s00431-025-06138-0

Brain oxygenation monitoring during neonatal stabilization ... This meta-analysis suggests that CrSO2-guided interventions may offer a meaningful advantage in preterm infant resuscitation after birth, improving survival ...

2. nature.com nature.com/articles/pr2015266

The SafeBoosC II randomized trial: treatment guided by ... The SafeBoosC phase II multicentre randomized clinical trial investigated the benefits and harms of monitoring cerebral oxygenation by ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4841944/

Cerebral oximetry in preterm infants: an agenda for ... The goals for research include testing the benefit and harms of cerebral oximetry in large-scale randomized trials, improved definition of the hypoxic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9489653/

A phase-II clinical trial of targeted cerebral near infrared ... The primary outcomes were mortality and severe brain injury (high grade intraventricular hemorrhage [IVH] or white matter injury) on 30-day cranial ultrasound.

5. scholarlyexchange.childrensmercy.org scholarlyexchange.childrensmercy.org/cgi/viewcontent.cgi?article=7022&context=papers

The SafeBoosC-III trial and the future of cerebral oximetry- ... Very few clinical trials have attempted to use a complex, algorithm-based, multitiered approach to address altered physiological indices to ...

6. nature.com nature.com/articles/s41372-021-00946-6

Neonatal NIRS monitoring: recommendations for data ... Near-infrared spectroscopy (NIRS) can safely and non-invasively estimate cerebral oxygenation, a correlate of cerebral perfusion, offering ...

7. tp.amegroups.org tp.amegroups.org/article/view/125950/html

The SafeBoosC-III trial and the future of cerebral oximetry ... The SafeBoosC-III trial and the future of cerebral oximetry-guided interventions in preterm infants—time to pause and reset?

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6483788/

Cerebral near‐infrared spectroscopy monitoring for prevention ... Cerebral NIRS monitoring could benefit the clinical outcomes of preterm infants because NIRS has the potential to alert healthcare workers when cerebral ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S1526054225000296

Towards standardized and clinically relevant definitions of ... A randomised crossover trial of clinical algorithm for oxygen saturation targeting in preterm infants with frequent desaturation episodes ...