IVH- Intraventricular HemorrhageDOXIENCT04413097
Delayed Cord Clamping With Oxygen In Extremely Low Gestation Infants
A study testing Delayed Cord Clamping with Low Oxygen concentration and Delayed Cord Clamping with High Oxygen concentration in people with IVH- Intraventricular Hemorrhage and Extreme Prematurity, run by Sharp HealthCare at 3 sites in United States.
Trial summary
This study is being conducted to compare the incidence of preterm infants (up to 28+6 weeks GA) who achieve a peripheral oxygen saturation of 80 percent by 5 minutes of life (MOL) given mask CPAP/PPV with an FiO2 of 1.0 during DCC for 90 seconds (HI Group) to infants given mask CPAP/PPV with an FiO2 of .30 during DCC… Read more about this study
- Who is it for?
- Ages 22 to 28 weeks
- Conditions the study is for
- IVH- Intraventricular Hemorrhage, Extreme Prematurity, Hypoxia Neonatal
- What is being tested?
- Delayed Cord Clamping with Low Oxygen concentration and Delayed Cord Clamping with High Oxygen concentration
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 3 sitesUnited States
- Study dates
- 17 Nov 2021to 1 Feb 2027
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 28 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- up to 28+6 weeks Gestational age
- Single and Multiple pregnancy
- All modes of delivery (vaginally or caesarean section)
Who cannot join
- Parents decline consent
- Congenital anomalies of the newborn
- Bleeding Accreta
- Monochorionic multiples with evidence of TTTS
- Fetal or maternal risk (i.e. compromise)
- Preterm Premature Rupture of Membranes prior to 20 weeks gestation
- Parents request no resuscitation
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of California Davis
Davis, California, 95817
University of California San Diego Jacobs Medical Center
San Diego, California, 92037
Sharp Mary Birch Hospital for Women and Newborns
San Diego, California, 92123
About this study
This study is being conducted to compare the incidence of preterm infants (up to 28+6 weeks GA) who achieve a peripheral oxygen saturation of 80 percent by 5 minutes of life (MOL) given mask CPAP/PPV with an FiO2 of 1.0 during DCC for 90 seconds (HI Group) to infants given mask CPAP/PPV with an FiO2 of .30 during DCC for 90 seconds (LO Group).
Read the detailed description
Prenatal consent will be obtained on infant's with estimated gestational age up to 28+6 weeks. Shortly before delivery, infant's will be randomly assigned to receive either Low oxygen concentration (FiO2 .30) OR High oxygen concentration (FiO2 1.0) during 90 seconds of delayed cord clamping.
Randomization and intervention will remain blinded to the clinical care team during the entire study period. The research team member will open a randomization card when notified of a subject's impending birth, review the protocol with the obstetric provider performing the procedure, set-up the sterile stabilization bed, and note the time it takes from delivery until the clamping and cutting of the umbilical cord in both groups.
The research team member will set the oxygen blender as indicated by the randomization card and cover the blender to blind the FiO2 setting. The research team member will not be involved in the clinical care of the infant. The oxygen blender will be concealed from the clinical care team to ensure resuscitation maneuvers will not be biased.
Data will be submitted to the statistician, who will remain blinded to the intervention for the duration of the study.
At delivery, the infant will be placed on a platform that allows the infant to be close to the mother and the umbilical cord to remain intact for DCC. These beds are equipped with an oxygen blender, humidifier, t-piece resuscitator with mask, necessary to provide CPAP/PPV. At some centers the bed will be equipped with a radian warmer (Ceramotherm, Wyer GmbH, Germany) to maintain thermoregulation on the infant during delayed cord clamping.
If an infant is randomized to the DCC and Low Oxygen concentration (DCC LO group), the following procedure will ensue:
During delayed cord clamping, the infant will be gently stimulated by drying the infant with a sterile towel and provide CPAP by 30 seconds of life. During delayed cord clamping, breathing assistance with CPAP of 5 cm H20 and a FiO2 0.3 will be provided.
If an infant is randomized to the DCC and High Oxygen concentration (DCC HI group), the following procedure will ensue:
During delayed cord clamping, the infant will be gently stimulated by drying the infant with a sterile towel and provide CPAP by 30 seconds of life. During delayed cord clamping, breathing assistance with CPAP of 5 cm H20 and a FiO2 1.0 will be provided.
Patency of the airway in both groups will be assessed by a Colorimetric CO2 detector. Lack of color change will indicate that the airway is not patent (obstructed), the pressure is not sufficient to expand the lungs, there was excessive air leak, or there was no or inadequate pulmonary blood flow. If there is no color change, the neonatal provider will reposition and reattempt to open the airway, if no improvement they will initiate PPV (starting PIP of 20 cm H20) by 60 seconds of life. Cord clamping will occur at 90 seconds or greater and the infant will be transferred to a standard neonatal warmer and resuscitated per NRP guidelines.
Additionally, when available heart rate data will be collected using a non-invasive dry-electrode monitor, (NeoBeat, Laerdal Medical, Stavanger, Norway) and applied over the infant's chest or abdomen to provide continuous display of heart rate during 90 seconds of DCC.
Pulse oximetry, ECG sensors and Near-Infrared Spectroscopy (NIRS) sensors will be applied after cord clamping. The NIRS sensor will be placed on the infant's forehead. Cerebral StO2, SpO2, blood pressure (once in the NICU) and Heart rate will be recorded every two seconds and linked with other variables. These variables will continue to be recorded for the first 24 hours of life.
Blood sample will be collected at two different time points: Cord blood sample (T1: Cord blood collected after the cord is cut) and at 2 hours of life or NICU admission (T2). This is extra few drops of blood that is drawn from the baby for medical purposes (cord blood from cord gases and admission blood work up).
Samples will be tested for oxidized and reduced glutathione which are the most reliable and comprehensive biomarkers of oxidative stress.
- Conditions
- IVH- Intraventricular Hemorrhage, Extreme Prematurity, Hypoxia Neonatal, Hyperoxia, Respiratory Insufficiency
- Being tested
- Delayed Cord Clamping with Low Oxygen concentration, Delayed Cord Clamping with High Oxygen concentration
- Keywords
- Delayed Cord Clamping, IVH- Intraventricular Hemorrhage, Hyperoxia in Neonates, Hypoxia Neonatal, Continuous Positive Airway Pressure (CPAP)
- Medical subject headings
- Asphyxia Neonatorum, Hyperoxia, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Delayed Cord Clamping with Low Oxygen concentrationProcedure or surgery
Also called DCC with Low Oxygen concentration, DCC LO group
During delayed umbilical cord clamping of 90 seconds, breathing assistance with CPAP/PPV and low oxygen concentration (FiO2 0.30) will be provided.
Delayed Cord Clamping with High Oxygen concentrationProcedure or surgery
Also called DCC with High Oxygen concentration, DCC HI group
During delayed umbilical cord clamping of 90 seconds, breathing assistance with CPAP/PPV and high oxygen concentration (FiO2 1.0) will be provided.
| Study group | Role | What they receive |
|---|---|---|
| DCC and Low Oxygen Concentration | Active comparator | 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. Receives: Procedure: Delayed Cord Clamping with Low Oxygen concentration |
| DCC and High Oxygen Concentration | Experimental | 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. Receives: Procedure: Delayed Cord Clamping with High Oxygen concentration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Achieving a Peripheral Oxygen Saturation of 80 Percent by 5 Minutes After Birth
Indicates whether enrolled infants achieved a preductal peripheral oxygen saturation (SpO₂) of at least 80% by 5 minutes after birth. Preductal SpO₂ was measured using pulse oximetry, with the probe placed on the infant's right hand, in accordance with standard neonatal resuscitation practices. Following completion of the deferred cord-clamping period and clamping and cutting of the umbilical cord, SpO₂ monitoring was initiated during delivery room resuscitative care.The assessment time point was defined as 5 minutes after delivery. When continuous SpO₂ monitoring tracings were available, these data were reviewed to determine whether the infant achieved a preductal SpO₂ of at least 80% by the 5-minute time point. When continuous tracings were not available, contemporaneous nursing documentation was reviewed in a blinded manner to determine whether the SpO₂ threshold was achieved. The outcome was analyzed as a dichotomous measure (SpO₂ ≥80% vs <80%) using an intention-to-treat approach
Measured: Assessed during the period from arrival at the Panda bed warmer for initial resuscitation until 5 minutes after birth.
Secondary outcomes (7)
Any Intraventricular Hemorrhage (Grades 1-4)
Presence of any intraventricular hemorrhage (IVH), defined as Grade 1 through Grade 4, as diagnosed by cranial ultrasound performed according to routine neonatal care practices. IVH grading followed standard neonatal neuroimaging criteria, and results were abstracted from clinical radiology reports.
Measured: From birth to initial neonatal intensive care unit discharge, up to 6 months corrected age
Grade III and IV Intraventricular Hemorrhage
Proportion of participants with severe intraventricular hemorrhage (Grades 3-4), defined as Grade 3 intraventricular hemorrhage with ventricular dilation or Grade 4 intraventricular hemorrhage with extension into the brain parenchyma, as classified according to the Papile grading system, assessed by cranial ultrasound.
Measured: Birth to initial neonatal intensive care unit discharge, up to 6 months corrected age
Mean Heart Rate (BPM) in the First 10 Minutes of Life
Mean heart rate, expressed in beats per minute (BPM), of participants during the first 10 minutes of life. Heart rate is assessed in accordance with standard neonatal resuscitation monitoring practices using continuous electrocardiographic (ECG) monitoring or pulse oximetry, when available, or by auscultation or palpation if electronic monitoring is not feasible. Heart rate values obtained during the immediate post-birth period are recorded at regular intervals or continuously, and the outcome is reported as the mean BPM for each newborn across the first 10 minutes of life.
Measured: Assessed during the period from arrival at the Panda bed warmer for initial resuscitation until 10 minutes after birth.
Resuscitation Interventions: Endotracheal Intubation
Number of participants who undergo endotracheal intubation during neonatal resuscitation immediately following delivery. Intubation is defined as the placement of an endotracheal tube into the infant's trachea by a trained provider as part of resuscitative care in the delivery room. The outcome is recorded for each newborn during the immediate post-birth period and reported as the total number of infants requiring intubation.
Measured: From birth up to 30 minutes after birth
Resuscitation Interventions: Administration of Exogenous Surfactant
Number of participants who receive administration of exogenous surfactant during neonatal resuscitation immediately following birth. Administration of surfactant is defined, per Neonatal Resuscitation Program (NRP) guidelines, as the delivery of exogenous surfactant to the newborn, typically via an endotracheal tube, as part of advanced delivery room respiratory support. The outcome is assessed for each newborn during the immediate post-birth resuscitation period and reported as the total number of infants who receive exogenous surfactant.
Measured: From birth up to 30 minutes after birth.
Resuscitation Intervention: Chest Compressions
Number of participants who receive chest compressions during neonatal resuscitation immediately following birth. Chest compressions are defined, per Neonatal Resuscitation Program (NRP) guidelines, as coordinated cardiac compressions as part of advanced resuscitative care in the delivery room. The outcome is assessed for each newborn during the immediate post-birth resuscitation period and reported as the total number of infants who receive chest compressions.
Measured: Birth up to 30 minutes after birth
Resuscitation Intervention: Epinephrine Administration
Number of participants who receive epinephrine administration during neonatal resuscitation immediately following birth. Epinephrine administration is defined, per Neonatal Resuscitation Program (NRP) guidelines, as the delivery of epinephrine via an approved route (intravenous, intraosseous, or endotracheal) as part of advanced resuscitative care in the delivery room. The outcome is assessed for each newborn during the immediate post-birth resuscitation period and reported as the total number of infants who receive epinephrine.
Measured: Assessed during the period from arrival at the Panda bed warmer for initial resuscitation until 30 minutes after birth.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2020
- Study start17 Nov 2021
- Primary completion19 May 2025
- Study completion1 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (60)Papers the sponsor has linked to this study.
- Other trials for IVH- Intraventricular HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sharp HealthCare
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Sharp Mary Birch Hospital for Women & Newborns
- Responsible party
- Principal investigator, Anup Katheria, M.D., Sharp HealthCare
- Investigators
- Anup Katheria, MD, Principal investigator, Sharp HealthCare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04413097
- Sponsor's protocol ID
- DOXIE
- Other IDs
- 5R03HD105224-02
- Acronym
- DOXIE
- Status last verified
- May 2026
- First submitted
- 27 May 2020
- Last updated
- 15 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be made available per NICHD requirements (National Institute of Child Health and Human Development)
Publications
Mercer JS, McGrath MM, Hensman A, Silver H, Oh W. Immediate and delayed cord clamping in infants born between 24 and 32 weeks: a pilot randomized controlled trial. J Perinatol. 2003 Sep;23(6):466-72. doi: 10.1038/sj.jp.7210970.
PubMed 13679933Rabe H, Jewison A, Fernandez Alvarez R, Crook D, Stilton D, Bradley R, Holden D; Brighton Perinatal Study Group. Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates: a randomized controlled trial. Obstet Gynecol. 2011 Feb;117(2 Pt 1):205-211. doi: 10.1097/AOG.0b013e3181fe46ff.
PubMed 21252731Mercer JS, Vohr BR, McGrath MM, Padbury JF, Wallach M, Oh W. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics. 2006 Apr;117(4):1235-42. doi: 10.1542/peds.2005-1706.
PubMed 16585320Hofmeyr GJ, Bolton KD, Bowen DC, Govan JJ. Periventricular/intraventricular haemorrhage and umbilical cord clamping. Findings and hypothesis. S Afr Med J. 1988 Jan 23;73(2):104-6.
PubMed 3340910Hofmeyr GJ, Gobetz L, Bex PJ, Van der Griendt M, Nikodem C, Skapinker R, Delahunt T. Periventricular/intraventricular hemorrhage following early and delayed umbilical cord clamping. A randomized controlled trial. Online J Curr Clin Trials. 1993 Dec 29;Doc No 110:[2002 words; 26 paragraphs].
PubMed 8305996Rabe H, Reynolds G, Diaz-Rossello J. Early versus delayed umbilical cord clamping in preterm infants. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD003248. doi: 10.1002/14651858.CD003248.pub2.
PubMed 15495045Fogarty M, Osborn DA, Askie L, Seidler AL, Hunter K, Lui K, Simes J, Tarnow-Mordi W. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018 Jan;218(1):1-18. doi: 10.1016/j.ajog.2017.10.231. Epub 2017 Oct 30.
PubMed 29097178Wyllie J, Perlman JM, Kattwinkel J, Wyckoff MH, Aziz K, Guinsburg R, Kim HS, Liley HG, Mildenhall L, Simon WM, Szyld E, Tamura M, Velaphi S; Neonatal Resuscitation Chapter Collaborators. Part 7: Neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation. 2015 Oct;95:e169-201. doi: 10.1016/j.resuscitation.2015.07.045. Epub 2015 Oct 15. No abstract available.
PubMed 26477424Polglase GR, Dawson JA, Kluckow M, Gill AW, Davis PG, Te Pas AB, Crossley KJ, McDougall A, Wallace EM, Hooper SB. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping) improves systemic and cerebral oxygenation in preterm lambs. PLoS One. 2015 Feb 17;10(2):e0117504. doi: 10.1371/journal.pone.0117504. eCollection 2015.
PubMed 25689406Hooper SB, Te Pas AB, Lang J, van Vonderen JJ, Roehr CC, Kluckow M, Gill AW, Wallace EM, Polglase GR. Cardiovascular transition at birth: a physiological sequence. Pediatr Res. 2015 May;77(5):608-14. doi: 10.1038/pr.2015.21. Epub 2015 Feb 4.
PubMed 25671807Bhatt S, Polglase GR, Wallace EM, Te Pas AB, Hooper SB. Ventilation before Umbilical Cord Clamping Improves the Physiological Transition at Birth. Front Pediatr. 2014 Oct 20;2:113. doi: 10.3389/fped.2014.00113. eCollection 2014.
PubMed 25368858Katheria A, Reister F, Essers J, Mendler M, Hummler H, Subramaniam A, Carlo W, Tita A, Truong G, Davis-Nelson S, Schmolzer G, Chari R, Kaempf J, Tomlinson M, Yanowitz T, Beck S, Simhan H, Dempsey E, O'Donoghue K, Bhat S, Hoffman M, Faksh A, Arnell K, Rich W, Finer N, Vaucher Y, Khanna P, Meyers M, Varner M, Allman P, Szychowski J, Cutter G. Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants. JAMA. 2019 Nov 19;322(19):1877-1886. doi: 10.1001/jama.2019.16004.
PubMed 31742630Katheria AC, Hassen K, Rich W, Poeltler D, Finer N. Resuscitation outcomes of infants that do not achieve a 5 min target SpO2 saturation. J Perinatol. 2019 Dec;39(12):1635-1639. doi: 10.1038/s41372-019-0491-x. Epub 2019 Sep 5.
PubMed 31488904Oei JL, Finer NN, Saugstad OD, Wright IM, Rabi Y, Tarnow-Mordi W, Rich W, Kapadia V, Rook D, Smyth JP, Lui K, Vento M. Outcomes of oxygen saturation targeting during delivery room stabilisation of preterm infants. Arch Dis Child Fetal Neonatal Ed. 2018 Sep;103(5):F446-F454. doi: 10.1136/archdischild-2016-312366. Epub 2017 Oct 7.
PubMed 28988158Katheria A, Poeltler D, Durham J, Steen J, Rich W, Arnell K, Maldonado M, Cousins L, Finer N. Neonatal Resuscitation with an Intact Cord: A Randomized Clinical Trial. J Pediatr. 2016 Nov;178:75-80.e3. doi: 10.1016/j.jpeds.2016.07.053. Epub 2016 Aug 26.
PubMed 27574999
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Delayed Cord Clamping With Oxygen In Extremely Low Gestation Infants
- ClinicalTrials.gov ID
- NCT04413097
- Acronym / sponsor ID
- DOXIE / DOXIE
- Conditions
- IVH- Intraventricular Hemorrhage, Extreme Prematurity, Hypoxia Neonatal, Hyperoxia, Respiratory Insufficiency
- Keywords
- Delayed Cord Clamping, IVH- Intraventricular Hemorrhage, Hyperoxia in Neonates, Hypoxia Neonatal, Continuous Positive Airway Pressure (CPAP)
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 140 participants (actual)
- Lead sponsor
- Sharp HealthCareUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Sharp Mary Birch Hospital for Women & Newborns
- Study start
- 17 Nov 2021 (actual)
- Primary completion
- 19 May 2025 (actual)
- Study completion
- 1 Feb 2027 (estimated)
- First posted
- 2 Jun 2020 (actual)
- Results
- Posted 15 Oct 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being conducted to compare the incidence of preterm infants (up to 28+6 weeks GA) who achieve a peripheral oxygen saturation of 80 percent by 5 minutes of life (MOL) given mask CPAP/PPV with an FiO2 of 1.0 during DCC for 90 seconds (HI Group) to infants given mask CPAP/PPV with an FiO2 of .30 during DCC for 90 seconds (LO Group).
Detailed description
Prenatal consent will be obtained on infant's with estimated gestational age up to 28+6 weeks. Shortly before delivery, infant's will be randomly assigned to receive either Low oxygen concentration (FiO2 .30) OR High oxygen concentration (FiO2 1.0) during 90 seconds of delayed cord clamping.
Randomization and intervention will remain blinded to the clinical care team during the entire study period. The research team member will open a randomization card when notified of a subject's impending birth, review the protocol with the obstetric provider performing the procedure, set-up the sterile stabilization bed, and note the time it takes from delivery until the clamping and cutting of the umbilical cord in both groups.
The research team member will set the oxygen blender as indicated by the randomization card and cover the blender to blind the FiO2 setting. The research team member will not be involved in the clinical care of the infant. The oxygen blender will be concealed from the clinical care team to ensure resuscitation maneuvers will not be biased.
Data will be submitted to the statistician, who will remain blinded to the intervention for the duration of the study.
At delivery, the infant will be placed on a platform that allows the infant to be close to the mother and the umbilical cord to remain intact for DCC. These beds are equipped with an oxygen blender, humidifier, t-piece resuscitator with mask, necessary to provide CPAP/PPV. At some centers the bed will be equipped with a radian warmer (Ceramotherm, Wyer GmbH, Germany) to maintain thermoregulation on the infant during delayed cord clamping.
If an infant is randomized to the DCC and Low Oxygen concentration (DCC LO group), the following procedure will ensue:
During delayed cord clamping, the infant will be gently stimulated by drying the infant with a sterile towel and provide CPAP by 30 seconds of life. During delayed cord clamping, breathing assistance with CPAP of 5 cm H20 and a FiO2 0.3 will be provided.
If an infant is randomized to the DCC and High Oxygen concentration (DCC HI group), the following procedure will ensue:
During delayed cord clamping, the infant will be gently stimulated by drying the infant with a sterile towel and provide CPAP by 30 seconds of life. During delayed cord clamping, breathing assistance with CPAP of 5 cm H20 and a FiO2 1.0 will be provided.
Patency of the airway in both groups will be assessed by a Colorimetric CO2 detector. Lack of color change will indicate that the airway is not patent (obstructed), the pressure is not sufficient to expand the lungs, there was excessive air leak, or there was no or inadequate pulmonary blood flow. If there is no color change, the neonatal provider will reposition and reattempt to open the airway, if no improvement they will initiate PPV (starting PIP of 20 cm H20) by 60 seconds of life. Cord clamping will occur at 90 seconds or greater and the infant will be transferred to a standard neonatal warmer and resuscitated per NRP guidelines.
Additionally, when available heart rate data will be collected using a non-invasive dry-electrode monitor, (NeoBeat, Laerdal Medical, Stavanger, Norway) and applied over the infant's chest or abdomen to provide continuous display of heart rate during 90 seconds of DCC.
Pulse oximetry, ECG sensors and Near-Infrared Spectroscopy (NIRS) sensors will be applied after cord clamping. The NIRS sensor will be placed on the infant's forehead. Cerebral StO2, SpO2, blood pressure (once in the NICU) and Heart rate will be recorded every two seconds and linked with other variables. These variables will continue to be recorded for the first 24 hours of life.
Blood sample will be collected at two different time points: Cord blood sample (T1: Cord blood collected after the cord is cut) and at 2 hours of life or NICU admission (T2). This is extra few drops of blood that is drawn from the baby for medical purposes (cord blood from cord gases and admission blood work up).
Samples will be tested for oxidized and reduced glutathione which are the most reliable and comprehensive biomarkers of oxidative stress.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DCC and Low Oxygen Concentration | Active comparator | Procedure: Delayed Cord Clamping with Low Oxygen concentrationDuring 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. |
| DCC and High Oxygen Concentration | Experimental | Procedure: Delayed Cord Clamping with High Oxygen concentrationDuring 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. |
Who may qualify
- Ages
- 22 to 28 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- up to 28+6 weeks Gestational age
- Single and Multiple pregnancy
- All modes of delivery (vaginally or caesarean section)
Key exclusion criteria (7 listed)
- Parents decline consent
- Congenital anomalies of the newborn
- Bleeding Accreta
- Monochorionic multiples with evidence of TTTS
- Fetal or maternal risk (i.e. compromise)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Delayed Cord Clamping with Low Oxygen concentrationAlso: DCC with Low Oxygen concentration, DCC LO groupDuring delayed umbilical cord clamping of 90 seconds, breathing assistance with CPAP/PPV and low oxygen concentration (FiO2 0.30) will be provided. | Procedure or surgery | DCC and Low Oxygen Concentration |
| Delayed Cord Clamping with High Oxygen concentrationAlso: DCC with High Oxygen concentration, DCC HI groupDuring delayed umbilical cord clamping of 90 seconds, breathing assistance with CPAP/PPV and high oxygen concentration (FiO2 1.0) will be provided. | Procedure or surgery | DCC and High Oxygen Concentration |
Primary outcome
Number of Participants Achieving a Peripheral Oxygen Saturation of 80 Percent by 5 Minutes After Birth
Time frame: Assessed during the period from arrival at the Panda bed warmer for initial resuscitation until 5 minutes after birth.
Indicates whether enrolled infants achieved a preductal peripheral oxygen saturation (SpO₂) of at least 80% by 5 minutes after birth. Preductal SpO₂ was measured using pulse oximetry, with the probe placed on the infant's right hand, in accordance with standard neonatal resuscitation practices. Following completion of the deferred cord-clamping period and clamping and cutting of the umbilical cord, SpO₂ monitoring was initiated during delivery room resuscitative care.The assessment time point was defined as 5 minutes after delivery. When continuous SpO₂ monitoring tracings were available, these data were reviewed to determine whether the infant achieved a preductal SpO₂ of at least 80% by the 5-minute time point. When continuous tracings were not available, contemporaneous nursing documentation was reviewed in a blinded manner to determine whether the SpO₂ threshold was achieved. The outcome was analyzed as a dichotomous measure (SpO₂ ≥80% vs <80%) using an intention-to-treat approach
7 secondary outcomes
Any Intraventricular Hemorrhage (Grades 1-4)
Time frame: From birth to initial neonatal intensive care unit discharge, up to 6 months corrected age
Grade III and IV Intraventricular Hemorrhage
Time frame: Birth to initial neonatal intensive care unit discharge, up to 6 months corrected age
Mean Heart Rate (BPM) in the First 10 Minutes of Life
Time frame: Assessed during the period from arrival at the Panda bed warmer for initial resuscitation until 10 minutes after birth.
Resuscitation Interventions: Endotracheal Intubation
Time frame: From birth up to 30 minutes after birth
Resuscitation Interventions: Administration of Exogenous Surfactant
Time frame: From birth up to 30 minutes after birth.
Resuscitation Intervention: Chest Compressions
Time frame: Birth up to 30 minutes after birth
Resuscitation Intervention: Epinephrine Administration
Time frame: Assessed during the period from arrival at the Panda bed warmer for initial resuscitation until 30 minutes after birth.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 13679933Mercer JS, McGrath MM, Hensman A, Silver H, Oh W. Immediate and delayed cord clamping in infants born between 24 and 32 weeks: a pilot randomized controlled trial. J Perinatol. 2003 Sep;23(6):466-72. doi: 10.1038/sj.jp.7210970.
- Background: PubMed 21252731Rabe H, Jewison A, Fernandez Alvarez R, Crook D, Stilton D, Bradley R, Holden D; Brighton Perinatal Study Group. Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates: a randomized controlled trial. Obstet Gynecol. 2011 Feb;117(2 Pt 1):205-211. doi: 10.1097/AOG.0b013e3181fe46ff.
- Background: PubMed 16585320Mercer JS, Vohr BR, McGrath MM, Padbury JF, Wallach M, Oh W. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics. 2006 Apr;117(4):1235-42. doi: 10.1542/peds.2005-1706.
- Background: PubMed 3340910Hofmeyr GJ, Bolton KD, Bowen DC, Govan JJ. Periventricular/intraventricular haemorrhage and umbilical cord clamping. Findings and hypothesis. S Afr Med J. 1988 Jan 23;73(2):104-6.
- Background: PubMed 8305996Hofmeyr GJ, Gobetz L, Bex PJ, Van der Griendt M, Nikodem C, Skapinker R, Delahunt T. Periventricular/intraventricular hemorrhage following early and delayed umbilical cord clamping. A randomized controlled trial. Online J Curr Clin Trials. 1993 Dec 29;Doc No 110:[2002 words; 26 paragraphs].
- Background: PubMed 15495045Rabe H, Reynolds G, Diaz-Rossello J. Early versus delayed umbilical cord clamping in preterm infants. Cochrane Database Syst Rev. 2004 Oct 18;(4):CD003248. doi: 10.1002/14651858.CD003248.pub2.
- Background: PubMed 29097178Fogarty M, Osborn DA, Askie L, Seidler AL, Hunter K, Lui K, Simes J, Tarnow-Mordi W. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018 Jan;218(1):1-18. doi: 10.1016/j.ajog.2017.10.231. Epub 2017 Oct 30.
- Background: PubMed 26477424Wyllie J, Perlman JM, Kattwinkel J, Wyckoff MH, Aziz K, Guinsburg R, Kim HS, Liley HG, Mildenhall L, Simon WM, Szyld E, Tamura M, Velaphi S; Neonatal Resuscitation Chapter Collaborators. Part 7: Neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Resuscitation. 2015 Oct;95:e169-201. doi: 10.1016/j.resuscitation.2015.07.045. Epub 2015 Oct 15. No abstract available.
- Background: PubMed 25689406Polglase GR, Dawson JA, Kluckow M, Gill AW, Davis PG, Te Pas AB, Crossley KJ, McDougall A, Wallace EM, Hooper SB. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping) improves systemic and cerebral oxygenation in preterm lambs. PLoS One. 2015 Feb 17;10(2):e0117504. doi: 10.1371/journal.pone.0117504. eCollection 2015.
- Background: PubMed 25671807Hooper SB, Te Pas AB, Lang J, van Vonderen JJ, Roehr CC, Kluckow M, Gill AW, Wallace EM, Polglase GR. Cardiovascular transition at birth: a physiological sequence. Pediatr Res. 2015 May;77(5):608-14. doi: 10.1038/pr.2015.21. Epub 2015 Feb 4.
- Background: PubMed 25368858Bhatt S, Polglase GR, Wallace EM, Te Pas AB, Hooper SB. Ventilation before Umbilical Cord Clamping Improves the Physiological Transition at Birth. Front Pediatr. 2014 Oct 20;2:113. doi: 10.3389/fped.2014.00113. eCollection 2014.
- Background: PubMed 31742630Katheria A, Reister F, Essers J, Mendler M, Hummler H, Subramaniam A, Carlo W, Tita A, Truong G, Davis-Nelson S, Schmolzer G, Chari R, Kaempf J, Tomlinson M, Yanowitz T, Beck S, Simhan H, Dempsey E, O'Donoghue K, Bhat S, Hoffman M, Faksh A, Arnell K, Rich W, Finer N, Vaucher Y, Khanna P, Meyers M, Varner M, Allman P, Szychowski J, Cutter G. Association of Umbilical Cord Milking vs Delayed Umbilical Cord Clamping With Death or Severe Intraventricular Hemorrhage Among Preterm Infants. JAMA. 2019 Nov 19;322(19):1877-1886. doi: 10.1001/jama.2019.16004.
- Individual participant dataSharing planned: Yes. Data will be made available per NICHD requirements (National Institute of Child Health and Human Development)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anup Katheria, MD principal investigator
Sharp HealthCare
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Delayed Cord Clamping with Low Oxygen concentration and Delayed Cord Clamping with High Oxygen concentration in people with IVH- Intraventricular Hemorrhage and Extreme Prematurity, run by Sharp HealthCare at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Oct 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Achieving a Peripheral Oxygen Saturation of 80 Percent by 5 Minutes After Birth (time frame: Assessed during the period from arrival at the Panda bed warmer for initial resuscitation until 5 minutes after birth.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04413097, which also lists 60 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.