Delayed Cord Clamping with Oxygen for Premature Birth

(DOXIE Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Anup Katheria, MD

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Sharp HealthCare

Disqualifiers: Congenital anomalies, Bleeding Accreta, TTTS, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests whether giving preterm babies different oxygen levels while delaying umbilical cord clamping helps them breathe better. It focuses on very early preterm infants who often have trouble breathing. The goal is to see which method helps these babies get enough oxygen in their blood more quickly.

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 Delayed Cord Clamping with Oxygen for Premature Birth?

Research suggests that physiological-based cord clamping (PBCC), which is part of the treatment, helps stabilize blood flow and improve outcomes in very preterm infants by allowing better lung and heart function. Additionally, delayed umbilical cord clamping is known to increase blood volume in newborns, which can be beneficial for premature babies. ^{1 2 3 4 5}

Is delayed cord clamping safe for premature infants?

The research on delayed cord clamping (DCC) in preterm infants suggests it is generally safe, as it does not increase the need for inotropic support (medications that help the heart pump blood) or affect mean arterial blood pressure (average blood pressure in the arteries). ^{6 7 8 9 10}

How is the treatment of delayed cord clamping with oxygen for premature birth different from other treatments?

Delayed cord clamping with oxygen for premature birth is unique because it involves waiting to clamp the umbilical cord until the baby's lungs are working properly, which helps stabilize blood flow and reduce potential brain injury. This approach, known as physiological-based cord clamping (PBCC), contrasts with immediate cord clamping and aims to improve the baby's transition to life outside the womb. ^{1 2 5 11 12}

Research Team

Anup Katheria, MD

Principal Investigator

Sharp HealthCare

Eligibility Criteria

This trial is for preterm infants born up to 28+6 weeks gestational age, from any type of delivery and pregnancy. It's not for those with early membrane rupture before 20 weeks, congenital anomalies, fetal/maternal compromise, or if parents decline consent or resuscitation.

Inclusion Criteria

I have given birth, regardless of the method.

You are pregnant with one baby or more than one baby.

I am currently 28 weeks and 6 days pregnant or less.

Exclusion Criteria

There is a risk to the mother or baby.

My twins share a placenta and have twin-to-twin transfusion syndrome.

I have been diagnosed with bleeding accreta.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Infants receive delayed cord clamping with either high or low oxygen concentration for 90 seconds

Immediate post-birth

1 visit (in-person)

Initial Monitoring

Infants are monitored for oxygen saturation, heart rate, and other vital signs in the first 24 hours of life

24 hours

Follow-up

Participants are monitored for safety and effectiveness after the intervention, including assessments for sepsis, intraventricular hemorrhage, and other outcomes

Up to 6 months corrected gestational age

Treatment Details

Interventions

• Delayed Cord Clamping with High Oxygen concentration (NA)
• Delayed Cord Clamping with Low Oxygen concentration (NA)

Trial Overview The study compares two groups of extremely premature babies during delayed cord clamping: one receives high oxygen concentration (100%) and the other low oxygen concentration (30%), to see which helps achieve better oxygen levels by 5 minutes after birth.

Participant Groups

Group I: DCC and High Oxygen Concentration Experimental Treatment 1 Intervention

During 90 seconds of delayed cord clamping, the infant will receive gentle stimulation and start CPAP by 30 seconds of life at an FiO2 1.0, with CPAP of 5 cmH20. If the infant is apneic or there is no Pedicap color change the team will begin positive pressure ventilation (starting PIP of 20 cmH20) by 60 seconds of life. The infant will remain on this support up until the umbilical cord is clamped at 90 seconds or greater. Once the cord is clamped the infant resuscitation will continue according to unit protocol.

Group II: DCC and Low Oxygen Concentration Active Control 1 Intervention

During 90 seconds of delayed cord clamping, the infant will receive gentle stimulation and start CPAP by 30 seconds of life at an FiO2 .30, with CPAP of 5 cmH20. If the infant is apneic or there is no Pedicap color change the team will begin positive pressure ventilation (starting PIP of 20 cmH20) by 60 seconds of life. The infant will remain on this support up until the umbilical cord is clamped at 90 seconds or greater. Once the cord is clamped the infant resuscitation will continue according to unit protocol.

Who Is Running the Clinical Trial?

Sharp HealthCare

Lead Sponsor

Trials

42

Recruited

17,600+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Dr. Diana W. Bianchi

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Chief Executive Officer since 2016

MD from Stanford University

Dr. Alison Cernich

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Chief Medical Officer since 2020

PhD in Clinical Psychology from University of Maryland

Sharp Mary Birch Hospital for Women & Newborns

Collaborator

Trials

13

Recruited

6,600+

Findings from Research

The ABC3 trial is investigating whether physiological-based cord clamping (PBCC), which delays cord clamping until after the infant is stabilized, leads to better survival outcomes compared to time-based delayed cord clamping (TBCC) in very preterm infants, with a target sample size of 660 infants.

By allowing for lung aeration before clamping, PBCC may improve circulatory adaptation and reduce the risk of cardiac output decline, potentially leading to fewer cases of major cerebral and intestinal injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-study protocol for a multicentre randomised controlled trial. Knol, R., Brouwer, E., van den Akker, T., et al.[2022]

Physiologically based cord clamping (PBCC) effectively restored oxygenation and cardiac output in asphyxiated near-term lambs, similar to immediate cord clamping (ICC), but with less rebound hypertension, which is beneficial for brain health.

PBCC significantly reduced cerebrovascular injury compared to ICC, suggesting it may be a safer and more effective resuscitation method for asphyxiated newborns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologically based cord clamping stabilises cardiac output and reduces cerebrovascular injury in asphyxiated near-term lambs. Polglase, GR., Blank, DA., Barton, SK., et al.[2018]

A study involving 37 very preterm infants (born before 32 weeks) found that physiological-based cord clamping (PBCC) is at least as effective as standard delayed cord clamping (DCC) in stabilizing infants, with PBCC leading to faster respiratory stability.

The mean time to reach respiratory stability was shorter for PBCC (5:54 minutes) compared to DCC (7:07 minutes), demonstrating non-inferiority, while no significant differences were observed in maternal or neonatal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiological-based cord clamping in very preterm infants - Randomised controlled trial on effectiveness of stabilisation. Knol, R., Brouwer, E., van den Akker, T., et al.[2021]

The study compared extrauterine placental perfusion (EPP) and delayed cord clamping (DCC) in 60 very low birth weight infants, finding that EPP resulted in similar hematocrit levels to DCC, indicating it is a safe alternative.

Infants in the EPP group showed significantly better oxygenation during transition, with higher peripheral and cerebral oxygen saturation levels, suggesting potential benefits for their immediate health after birth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extrauterine Placental Perfusion and Oxygenation in Infants With Very Low Birth Weight: A Randomized Clinical Trial. Kuehne, B., Grüttner, B., Hellmich, M., et al.[2023]

In premature neonates, delayed umbilical cord clamping (45 seconds) is associated with higher hematocrit levels and less need for delivery room resuscitation, indicating improved blood volume and stability at birth.

The study found no significant differences in overall transfusion rates, peak bilirubin levels, or mortality between delayed and early umbilical cord clamping groups, suggesting that delayed clamping is a safe practice for these infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed umbilical cord clamping in premature neonates. Kaempf, JW., Tomlinson, MW., Kaempf, AJ., et al.[2022]

In a study of 158 premature infants, delayed cord clamping (DCC) resulted in higher admission hemoglobin levels and a lower incidence of high-grade intraventricular hemorrhage (IVH) compared to immediate cord clamping (ICC).

While DCC did not reduce the need for inotropic support or affect mean arterial blood pressure (MABP), it was associated with fewer blood transfusions and earlier discharge from the hospital.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed cord clamping and inotrope use in preterm infants. Vesoulis, ZA., Rhoades, J., Muniyandi, P., et al.[2019]

Delaying cord clamping for at least two to three minutes after birth does not increase the risk of postpartum hemorrhage in mothers, based on a review of 11 trials involving 2,989 participants.

Late cord clamping improves newborn iron levels, which can be beneficial for infants, especially in cases where nutrition may be lacking, but it also increases the risk of jaundice requiring phototherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cochrane Update: Effect of timing of umbilical cord clamping at birth of term infants on mother and baby outcomes. Neilson, JP.[2022]

A meta-analysis of 13 studies involving 837 pediatric patients found that normothermic cardiopulmonary bypass (NCPB) significantly reduces the need for revision surgery due to postoperative bleeding and lowers serum lactate and creatinine levels compared to hypothermic cardiopulmonary bypass (HCPB).

NCPB is shown to be as safe as HCPB while providing additional benefits in clinical outcomes for children undergoing simple congenital heart surgery, including shorter CPB times and fewer major adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Normothermic Cardiopulmonary Bypass in Pediatric Cardiac Surgery: A System Review and Meta-Analysis. Xiong, T., Pu, L., Ma, YF., et al.[2022]

Cardiopulmonary bypass (CPB) is generally safe for mothers, but it raises significant concerns about potential complications for the fetus, highlighting the need for careful consideration in timing surgical interventions.

When surgery is necessary before the second trimester, ethical dilemmas arise regarding the balance between the mother's autonomy and the rights of the fetus, especially in the context of changing maternal health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrauterine pregnancy and aortic valve replacement. Paulus, DA., Layon, AJ., Mayfield, WR., et al.[2019]

The centrifugal vortex blood pump (CVBP) significantly accelerates the re-warming of hypothermic trauma patients, achieving normothermia in an average of 85 minutes compared to 217 minutes with conventional methods, based on a study involving 16 pigs.

CVBP not only re-warms faster but also appears to help normalize clotting times more quickly, although it is associated with lower cardiac output and higher systemic vascular resistance, indicating the need for further research on its physiological effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Active internal re-warming using a centrifugal pump and heat exchanger following haemorrhagic shock, surgical trauma and hypothermia in a porcine model. Garraway, N., Brown, DR., Nash, D., et al.[2008]

Delayed umbilical cord clamping (DCC) resulted in significantly higher Apgar scores at 1 and 5 minutes for infants, indicating better immediate health outcomes compared to early cord clamping (ECC).

The DCC group showed a higher umbilical artery pO2 level, but overall, there were no clinically significant differences in blood gas parameters, suggesting that DCC does not require changes to clinical reference intervals for blood gas analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed cord clamping does not affect umbilical cord blood gas analysis. Tang, J., Fullarton, R., Samson, SL., et al.[2020]

In a study of 382 term deliveries, delayed cord clamping (DCC) did not significantly reduce maternal postpartum hemorrhage (PPH) compared to early cord clamping (ECC), with only a 1.2% difference in PPH rates.

The proportion of valid umbilical cord blood gas samples was similar between DCC and ECC groups, indicating that DCC is a feasible method without compromising the quality of blood sampling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial. Andersson, O., Hellström-Westas, L., Andersson, D., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-study protocol for a multicentre randomised controlled trial. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Physiologically based cord clamping stabilises cardiac output and reduces cerebrovascular injury in asphyxiated near-term lambs. [2018]

3. Ireland pubmed.ncbi.nlm.nih.gov

Physiological-based cord clamping in very preterm infants - Randomised controlled trial on effectiveness of stabilisation. [2021]

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

Extrauterine Placental Perfusion and Oxygenation in Infants With Very Low Birth Weight: A Randomized Clinical Trial. [2023]

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

Delayed umbilical cord clamping in premature neonates. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Delayed cord clamping and inotrope use in preterm infants. [2019]

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

Cochrane Update: Effect of timing of umbilical cord clamping at birth of term infants on mother and baby outcomes. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Safety of Normothermic Cardiopulmonary Bypass in Pediatric Cardiac Surgery: A System Review and Meta-Analysis. [2022]

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

Intrauterine pregnancy and aortic valve replacement. [2019]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Active internal re-warming using a centrifugal pump and heat exchanger following haemorrhagic shock, surgical trauma and hypothermia in a porcine model. [2008]

11. Germany pubmed.ncbi.nlm.nih.gov

Delayed cord clamping does not affect umbilical cord blood gas analysis. [2020]

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

Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial. [2013]