CClinicalTrials.gg
RecruitingNCT06408376Updated May 10, 2024

Physiological Umbilical Cord Clamping in Patients With Congenital Diaphragmatic Hernia. Clinical Trial

An interventional study of Physiological cord clamping in Umbilical Cord Clamping, Congenital Diaphragmatic Hernia and Delayed Umbilical Cord Separation, sponsored by Hospital JP Garrahan. Recruiting at 1 site in Argentina. Per ClinicalTrials.gov, last updated 2024-05-10.

Sponsored by Hospital JP Garrahan · Not applicable, Interventional, and Prevention

Phase
Not applicable
Study type
Interventional
Enrollment
80
Allocation
Randomized
Sex
All
01

Study summary

Congenital diaphragmatic hernia (CDH) is a malformation that affects 1 in every 3000 newborns. The diaphragm does not complete its closure during embryogenesis, which allows the abdominal organs to herniate into the thoracic cavity altering lung development. The lungs of patients with CDH are small, with a decreased surface area for gas exchange and developmental impair of the pulmonary vasculature, resulting in respiratory failure and pulmonary hypertension shortly after birth. When clamping the umbilical cord, a large part of the preload is abruptly excluded, generating an increase in vascular resistance, which in turn increase the afterload, resulting in a decrease in cardiac output. The output is restored by decreasing vascular resistance in pulmonary circuit after lung aeration upon receiving the preload of the right atrium, increasing pulmonary flow and thus sustaining the preload of the left ventricle. If pulmonary aeration occurs before clamping the umbilical cord, the pulmonary blood flow increases before placenta flow is lost, thus avoiding a decrease in cardiac output. This modality has been called physiological base cord clamping (PFC). The hypothesis is that PFC once ventilation has been established could prevent hypoxia and improve cardiac output in newborns with CDH and secondarily improve their hemodynamic parameters, stabilizing gas exchange and pulmonary hypertension during the first 24 hours of birth.

Read the detailed description
  • Type of study: Randomized clinical trial
  • Primary objective: To establish the effectiveness of PFC in reducing hypoxia and improving cardiac output compared to immediate postintubation clamping in newborns with CDH. To establish the safety and feasibility of PFC after pulmonary recruitment achieved post intubation.
  • Secondary objectives: describe the evolution of patients with CDH 24 hours after birth under pre-established conditions. Relate prenatal indices to the subsequent evolution of these patients. Describe maternal evolution and postpartum complications.
  • Population: Patients who attend the Fetal Diagnosis and Treatment program of Garrahan Children's Hospital and undergo prenatal diagnosis of CDH are possible candidates. The study will be carried out in the Neonatal Intensive Care Unit of said hospital.
  • Scope of the study: Garrahan Children's Hospital is a level 3 B pediatric hospital and national referral center located in Autonomous City of Buenos Aires, Argentina. Center that receives neonates with CDH referred from all over the country as well as from other countries in the region and carries out the relevant training for equal reception.
  • Block randomization: will be carried out on the same day, 2 hours before entering the delivery room
  • Intervention: Immediately after birth, the newborn will be placed on a mobile table, made to received these patients in the delivery room, at the level of the mother's womb, leaving the umbilical cord intact, intubated and gently ventilated (positive inspiration pressure (PIM) 15/25 - positive end expiratory pressure (PEEP)4 - fraction of inspired oxygen inspired oxygen fraction (FiO2) 50%), until saturation >85% and heart rate (HR) >100 or 10 timed minutes pass, whichever occurs first, the umbilical cord will be clamped and continued with the usual reception steps in accordance with the unit´s CDH reception protocol.
  • Sample size: To calculate the sample size, a prevalence of hemodynamic alterations of 60% was considered in the first 24 hours of life of patients with CDH, following unit statistics and the aforementioned bibliography. The estimated sample size with a relative reduction of 50%: reduction from 60% to 30% of hemodynamic alterations - Power of 80% - Two-tailed test - alpha 5%. 40 patients required in each branch.
02

Conditions studied

  • Umbilical Cord Clamping
  • Congenital Diaphragmatic Hernia
  • Delayed Umbilical Cord Separation
03

Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Prenatal diagnosis of congenital diaphragmatic hernia
  • gestational age >34 weeks
  • Informed consent signed by the patient's parents

Exclusion criteria

Exclusion Criteria:

  • Multiple gestation
  • Major malformation or fetal genetic anomaly diagnosed in the prenatal stage
  • Emergency cesarean section or maternal condition that prevents the approach
  • Lack of informed consent
04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Factorial assignment
Masking
Single (Participant)
Enrollment
80 participants (estimated)

Study arms

  • Experimental
    physiological umbilical cord clamping

    Immediately after birth, the newborn will be placed on a mobile table, made to receive these patients in the delivery room, at the level of the mother's womb, leaving the umbilical cord intact and will be intubated. The patient will be gently ventilated (PIM 15/25 - PEEP 4 - Fio2 50%), until saturation \>85% and HR\>100 or 10 timed minutes have elapsed, whichever occurs first, the umbilical cord will be clamped and the procedures continued usual reception steps according to the unit´s CDH reception protocol.

    Procedure: Physiological cord clamping

  • No intervention
    usual reception

    Immediately after birth, the newborn is placed on a mobile table, made to receive these patients in the delivery room, at the level of the mother's womb, leaving the umbilical cord intact will be intubated. According to the unit´s CDH reception protocol, patients with CDH cord clamping is done post intubation

Interventions

  • ProcedurePhysiological cord clamping

    Immediately after birth, the newborn with prenatal diagnosis of CDH will be placed on a mobile table, made to receive these patients in the delivery room, at the level of the mother's womb, leaving the umbilical cord intact and intubated. The patient will be gently ventilated (PIM 15/25 - PEEP 4 - Fio2 50%), until saturation \>85% and HR\>100 or 10 timed minutes have elapsed, whichever occurs first, the umbilical cord will be clamped.

05

What researchers measure

Primary outcomes

  1. Hemodynamic deterioration in the first 24 hours of life

    Hemodynamic deterioration in the first 24 hours of life (meeting 3 of 4 of the following criteria or entry to extracorporeal membrane oxygenation (ECMO) or Death). 1. Pre/post ductal saturation difference \>10% 2. Oxygenation index (IO) \>20 3. mean arterial pressure \< Percentile 50 or inotrope requirement 4. Lactic acid \>3 mmol/l

    Time frame: 24 hours of life

  2. complete delivery according group

    Complete the protocol in the delivery room pre-established according to randomization (yes/no)

    Time frame: delivery

Secondary outcomes

  1. Gestational age at diagnosis

    Gestational age at diagnosis of CDH in weeks

    Time frame: 1st day of life

  2. Lung heart rate index observed/expected LHR O/E

    lung heart rate index observed/expected (LHR O/E)

    Time frame: from 26 to 32 weeks of gestational age

  3. liver in thorax

    liver in thorax (yes/no) and %

    Time frame: from 26 to 32 weeks of gestational age

  4. stomach herniation

    stomach herniation (yes/no) and %

    Time frame: from 26 to 32 weeks of gestational age

  5. lung volumen

    lung volumen in RMI

    Time frame: from 26 to 32 weeks of gestational age

  6. Mcgoon

    Mcgoon Index in fetal echocardiogram

    Time frame: from 26 to 32 weeks of gestational age

  7. maternal hematocrit

    maternal hematocrit in gr/dl

    Time frame: 1 day before delivery

  8. Intubation time

    Time to intubation (minutes, seconds)

    Time frame: From delivery to intubation

  9. Cord clamping time

    Cord clamping time (minutes, seconds)

    Time frame: from delivery to cord clamping

  10. Advance resuscitation need on delivery room

    Requirement for advanced resuscitation (yes/no) (compressions, drugs, hypothermia)

    Time frame: from delivery to 30 minutes of life

  11. Time to reach heart rate (HR) >100

    Time to reach HR \>100 (minutes, seconds)

    Time frame: from delivery to 30 minutes of life

  12. Time to reach saturation (SAT) >85%

    Time to reach SAT \>85% (minutes, seconds)

    Time frame: from delivery to 30 minutes of life

  13. Cord PH value

    cord ph value

    Time frame: inmediatly after cord clampping

  14. Cord lactic acid value

    cord lactic acid value in mmol/l

    Time frame: inmediatly after cord clampping

  15. saturation at 10 minutes

    pre and post ductal saturation %

    Time frame: 10 minutes of life

  16. Arterial pressure at 10 minutes

    mean arterial tension in mmhg

    Time frame: 10 minutes of life

  17. placenta abruption

    Time for placental abruption (minutes, seconds)

    Time frame: 30 minutes of life

  18. Mother arterial tension after delivery

    mothers arterial mean tension after delivery in mmhg

    Time frame: 10 minutes after delivery

  19. Uterotonic use

    uterotonics use on mothers after delivery (yes/no)

    Time frame: 30 minutes after delivery

  20. Evolution of patient Blood preassure (BP)

    Blood pressure in mmhg

    Time frame: 2 - 4 hours and 24 hours of life

  21. Evolution of patient inotropes required

    Inotrope requirement (yes/no)

    Time frame: 2 - 4 hours and 24 hours of life

  22. Inhaled nitric oxide (NOi) requirement

    NOi requirement (yes/no)

    Time frame: 2 - 4 hours and 24 hours of life

  23. ventilation requirements on the first day

    Ventilatory mode / mean airway pressure (MAP)/ FIo2 %

    Time frame: 2 - 4 hours and 24 hours of life

  24. Oxygenation on the first day

    Partial arterial pressure of oxygen (PaO2) mmhg

    Time frame: 2 - 4 hours and 24 hours of life

  25. Oxygenation index (OI) on the first day

    OI

    Time frame: 2 - 4 hours and 24 hours of life

  26. near-infrared spectroscopy (Nirs) on the first day

    Cerebral and somatic NIRS

    Time frame: 2 - 4 hours and 24 hours of life

  27. B natriuretic peptide (BNP) on the first day

    B natriuretic peptide (BNP)

    Time frame: 24 hours of life

  28. PH value on the first day

    echocardiographic pulmonary hypertension PH (\<50% of systemic pressure, between 50-80% of systemic pressure, between 80 and 100% of systemic pressure, systemic, suprasystemic)

    Time frame: 6 and 24 hours of life

  29. cardiac malformations

    cardiac malformation (yes/no)

    Time frame: 6 hours of life

  30. Mortality

    Mortality (yes/no)

    Time frame: through study completion, an average of 1 year

  31. Admission to ECMO

    Admission to ECMO after the first 24 hours (yes/no)

    Time frame: through study completion, an average of 1 year

Other outcomes

  1. maternal age

    maternal age during pregnancy

    Time frame: through study completion, an average of 1 year

  2. maternal history

    maternal pathological history during pregnancy (yes/no)

    Time frame: through study completion, an average of 1 year

  3. baby weight

    Weight in grams

    Time frame: 30 minutes of life

  4. Patent ductus arteriosus (PAD) on the first day (size)

    Patent ductus arteriosus (PAD): size in milimeters

    Time frame: 6 and 24 hours of life

  5. Patent ductus arteriosus (PAD) on the first day (gradient)

    Patent ductus arteriosus (PAD): gradient

    Time frame: 6 and 24 hours of life

  6. Patent ductus arteriosus (PAD) on the first day (shunt direction)

    Patent ductus arteriosus (PAD): shunt direction

    Time frame: 6 and 24 hours of life

  7. Patent foramen ovale (PFO) on the first day (shunt direction)

    Patent foramen ovale (PFO): shunt direction.

    Time frame: 6 and 24 hours of life

  8. Right ventricle (RV) on the first day diameter

    Right ventricle (RV): RV diameter in milimeters

    Time frame: 6 and 24 hours of life

  9. Right ventricle (RV) on the first day TAPSE

    Right ventricle (RV): TAPSE

    Time frame: 6 and 24 hours of life

  10. Tricuspide Insufitienty

    tricuspide insufitienty

    Time frame: 6 and 24 hours of life

  11. Right ventricle funtion

    Right ventricle global disfuntion : no, mild, moderate or severe

    Time frame: 6 and 24 hours of life

  12. Left ventricle (LV) on the first day (eccentricity index)

    Left ventricle (LV): eccentricity index

    Time frame: 6 and 24 hours of life

  13. Left ventricle (LV) on the first day (ejection fraction)

    Left ventricle (LV): ejection fraction (EF)

    Time frame: 6 and 24 hours of life

  14. Left ventricle (LV) on the first day global funtion

    Left ventricle (LV) global disfuntion : no, global disfuntion : no, mild, moderate or severe

    Time frame: 6 and 24 hours of life

  15. Interventricular septum (IS) on the first day

    Interventricular septum: configuration

    Time frame: 6 and 24 hours of life

  16. Pulmonary hypertation grade on the first day

    Pulmonary hypertation: no, mild, moderate or severe

    Time frame: 6 and 24 hours of life

  17. Associated malformations

    Associated malformations (yes/no), which

    Time frame: 24 hours of life

  18. Chromosomopathy or genetic alteration

    Chromosomopathy or genetic alteration (yes/no), which

    Time frame: through study completion, an average of 1 year

  19. Hyperbilirubinemia

    Hyperbilirubinemia requiring phototherapy or exchange transfusion (yes/no)

    Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

  20. Early sepsis

    Early sepsis (yes/no)

    Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

  21. Omphalitis

    Omphalitis (yes/no)

    Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

  22. CDH surgery

    CDH surgery (yes/no), days of life

    Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

  23. Surgical classification

    Surgical classification of CDH (a-b-c-d)

    Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

  24. Days in neonatal intensive care unit (NICU)

    Days in NICU

    Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

06

Study locations

1 of 1 sites recruiting
  • Hospital de Pediatría S.A.M.I.C. "Prof. Dr. Juan P. Garrahan"
    Buenos Aires, C1245AAM, Argentina
    Recruiting
07

References and documents

Publications

  • Langham MR Jr, Kays DW, Ledbetter DJ, Frentzen B, Sanford LL, Richards DS. Congenital diaphragmatic hernia. Epidemiology and outcome. Clin Perinatol. 1996 Dec;23(4):671-88. PubMed 8982563 ↗
  • Keller RL. Antenatal and postnatal lung and vascular anatomic and functional studies in congenital diaphragmatic hernia: implications for clinical management. Am J Med Genet C Semin Med Genet. 2007 May 15;145C(2):184-200. doi: 10.1002/ajmg.c.30130. PubMed 17436304 ↗
  • Snoek KG, Reiss IK, Greenough A, Capolupo I, Urlesberger B, Wessel L, Storme L, Deprest J, Schaible T, van Heijst A, Tibboel D; CDH EURO Consortium. Standardized Postnatal Management of Infants with Congenital Diaphragmatic Hernia in Europe: The CDH EURO Consortium Consensus - 2015 Update. Neonatology. 2016;110(1):66-74. doi: 10.1159/000444210. Epub 2016 Apr 15. PubMed 27077664 ↗
  • Bhatt S, Alison BJ, Wallace EM, Crossley KJ, Gill AW, Kluckow M, te Pas AB, Morley CJ, Polglase GR, Hooper SB. Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs. J Physiol. 2013 Apr 15;591(8):2113-26. doi: 10.1113/jphysiol.2012.250084. Epub 2013 Feb 11. PubMed 23401615 ↗
  • Polglase 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 25689406 ↗
  • Hooper 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 25671807 ↗
  • Horn-Oudshoorn EJJ, Knol R, Te Pas AB, Hooper SB, Cochius-den Otter SCM, Wijnen RMH, Schaible T, Reiss IKM, DeKoninck PLJ. Perinatal stabilisation of infants born with congenital diaphragmatic hernia: a review of current concepts. Arch Dis Child Fetal Neonatal Ed. 2020 Jul;105(4):449-454. doi: 10.1136/archdischild-2019-318606. Epub 2020 Mar 13. PubMed 32170029 ↗
  • Hooper SB, Polglase GR, te Pas AB. A physiological approach to the timing of umbilical cord clamping at birth. Arch Dis Child Fetal Neonatal Ed. 2015 Jul;100(4):F355-60. doi: 10.1136/archdischild-2013-305703. Epub 2014 Dec 24. PubMed 25540147 ↗
  • Lefebvre C, Rakza T, Weslinck N, Vaast P, Houfflin-Debarge V, Mur S, Storme L; French CDH Study Group. Feasibility and safety of intact cord resuscitation in newborn infants with congenital diaphragmatic hernia (CDH). Resuscitation. 2017 Nov;120:20-25. doi: 10.1016/j.resuscitation.2017.08.233. Epub 2017 Aug 30. PubMed 28860014 ↗
  • Duley L, Dorling J, Pushpa-Rajah A, Oddie SJ, Yoxall CW, Schoonakker B, Bradshaw L, Mitchell EJ, Fawke JA; Cord Pilot Trial Collaborative Group. Randomised trial of cord clamping and initial stabilisation at very preterm birth. Arch Dis Child Fetal Neonatal Ed. 2018 Jan;103(1):F6-F14. doi: 10.1136/archdischild-2016-312567. Epub 2017 Sep 18. PubMed 28923985 ↗
  • Wyckoff MH, Aziz K, Escobedo MB, Kapadia VS, Kattwinkel J, Perlman JM, Simon WM, Weiner GM, Zaichkin JG. Part 13: Neonatal Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015 Nov 3;132(18 Suppl 2):S543-60. doi: 10.1161/CIR.0000000000000267. No abstract available. PubMed 26473001 ↗
  • Rabe H, Gyte GM, Diaz-Rossello JL, Duley L. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev. 2019 Sep 17;9(9):CD003248. doi: 10.1002/14651858.CD003248.pub4. PubMed 31529790 ↗
  • Katheria AC, Brown MK, Faksh A, Hassen KO, Rich W, Lazarus D, Steen J, Daneshmand SS, Finer NN. Delayed Cord Clamping in Newborns Born at Term at Risk for Resuscitation: A Feasibility Randomized Clinical Trial. J Pediatr. 2017 Aug;187:313-317.e1. doi: 10.1016/j.jpeds.2017.04.033. Epub 2017 May 16. PubMed 28526223 ↗
  • McGillick EV, Davies IM, Hooper SB, Kerr LT, Thio M, DeKoninck P, Yamaoka S, Hodges R, Rodgers KA, Zahra VA, Moxham AM, Kashyap AJ, Crossley KJ. Effect of lung hypoplasia on the cardiorespiratory transition in newborn lambs. J Appl Physiol (1985). 2019 Aug 1;127(2):568-578. doi: 10.1152/japplphysiol.00760.2018. Epub 2019 Jun 13. PubMed 31194603 ↗
  • Kashyap AJ, Hodges RJ, Thio M, Rodgers KA, Amberg BJ, McGillick EV, Hooper SB, Crossley KJ, DeKoninck PLJ. Physiologically based cord clamping improves cardiopulmonary haemodynamics in lambs with a diaphragmatic hernia. Arch Dis Child Fetal Neonatal Ed. 2020 Jan;105(1):18-25. doi: 10.1136/archdischild-2019-316906. Epub 2019 May 23. PubMed 31123056 ↗
  • Sakurai Y, Azarow K, Cutz E, Messineo A, Pearl R, Bohn D. Pulmonary barotrauma in congenital diaphragmatic hernia: a clinicopathological correlation. J Pediatr Surg. 1999 Dec;34(12):1813-7. doi: 10.1016/s0022-3468(99)90319-6. PubMed 10626861 ↗
  • Foglia EE, Ades A, Hedrick HL, Rintoul N, Munson DA, Moldenhauer J, Gebb J, Serletti B, Chaudhary A, Weinberg DD, Napolitano N, Fraga MV, Ratcliffe SJ. Initiating resuscitation before umbilical cord clamping in infants with congenital diaphragmatic hernia: a pilot feasibility trial. Arch Dis Child Fetal Neonatal Ed. 2020 May;105(3):322-326. doi: 10.1136/archdischild-2019-317477. Epub 2019 Aug 28. PubMed 31462406 ↗
  • Winter J, Kattwinkel J, Chisholm C, Blackman A, Wilson S, Fairchild K. Ventilation of Preterm Infants during Delayed Cord Clamping (VentFirst): A Pilot Study of Feasibility and Safety. Am J Perinatol. 2017 Jan;34(2):111-116. doi: 10.1055/s-0036-1584521. Epub 2016 Jun 15. PubMed 27305177 ↗
  • Katheria 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 ↗
  • Le Duc K, Mur S, Rakza T, Boukhris MR, Rousset C, Vaast P, Westlynk N, Aubry E, Sharma D, Storme L. Efficacy of Intact Cord Resuscitation Compared to Immediate Cord Clamping on Cardiorespiratory Adaptation at Birth in Infants with Isolated Congenital Diaphragmatic Hernia (CHIC). Children (Basel). 2021 Apr 26;8(5):339. doi: 10.3390/children8050339. PubMed 33925985 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT06408376
Lead sponsor
Hospital JP Garrahan
Responsible party
Mariela Jozefkowicz (Principal Investigator, Hospital JP Garrahan) — Principal investigator
First posted
May 10, 2024
Start date
Jun 14, 2022
Primary completion
Dec 31, 2026 (estimated)
Completion
Dec 31, 2026 (estimated)
Last update
May 10, 2024

Study contacts

Mariela Jozefkowicz
Contact
mjozefkowicz@garrahan.gov.ar
+5491164646270
Maria T Mazzucchelli
Contact
mtmazzu@gmail.com
+5491149170437
Mariela Jozefkowicz
principal investigator · Hospital JP Garrahan

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
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