search
Back to results

Physiological-based Cord Clamping in Congenital Diaphragmatic Hernia (PinC)

Primary Purpose

Hernias, Diaphragmatic, Congenital, Hernia; Diaphragm Defect, Congenital, Pulmonary Hypertension

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Physiological-based cord clamping
Sponsored by
Erasmus Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Hernias, Diaphragmatic, Congenital focused on measuring Congenital diaphragmatic hernia, Perinatal stabilisation, Resuscitation, Pulmonary hypertension, Birth defect, Physiological-based cord clamping

Eligibility Criteria

35 Weeks - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Left-sided CDH
  • Isolated CDH: no associated structural or genetic abnormalities that are diagnosed before birth
  • Gestational age at delivery ≥35.0 weeks
  • Parental written informed consent

Exclusion Criteria:

  • Right-sided or bilateral CDH
  • Gestational age at delivery <35.0 weeks
  • Maternal contraindications: anterior placenta praevia, placental abruption
  • High urgency caesarean section, with intended interval to delivery <15 min
  • Cases that have been treated during pregnancy with experimental drug therapy aiming to decrease the occurrence of pulmonary hypertension
  • Twin pregnancies in which the infant diagnosed with a CDH is born first
  • Multiple birth >2 (triplets or higher order)

Sites / Locations

  • Monash UniversityRecruiting
  • Medical University GrazRecruiting
  • University Hospitals leuvenRecruiting
  • Universitätskrankenhaus Bonn
  • Universitätsklinik Mannheim
  • Ospedale Pediatrico Bambino Gesu
  • Radboudumc University Medical CenterRecruiting
  • Erasmus MC University Medical Center - Sophia Children's HospitalRecruiting
  • Karolinska University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Physiological-based cord clamping

Immediate cord clamping

Arm Description

In PBCC, the Concord will be placed next to the bed of the mother and all equipment will be checked before the second stage of labour has started. The infant will be placed on the platform of the Concord immediately after birth, avoiding any traction or pressure on the cord and avoiding heat loss by radiation heating. The umbilical cord will not be clamped until the infant is considered respiratory stable, which is defined as the presence of a heart rate >100 bpm and preductal oxygen saturation >85%, while using an fraction of inspired oxygen (FiO2) of <0.5. The minimum and maximum times of cord clamping are three and ten minutes after birth, respectively. Oxytocin administration will be postponed until after cord clamping if there are no obstetric concerns. At any time, the attending neonatologist and obstetrician can decide that PBCC should not be performed or be interrupted. In that case, the infant can be placed on the standard resuscitation table for (further) stabilisation.

In the immediate cord clamping group, the cord will be clamped immediately after birth. The infant will then be transferred to the standard neonatal resuscitation table. After cord clamping, all infants will be managed according to the standardised neonatal management protocol for infants with a CDH, which is a consensus of current clinical guidelines by the CDH EURO consortium.

Outcomes

Primary Outcome Measures

Number of participants with pulmonary hypertension diagnosed in the first 24 hours after birth.
Pulmonary hypertension is present if at least 2 of the following 4 criteria are present or if the infant requires extracorporeal membrane oxygenation (ECMO) in the first 24 hours after birth: Right ventricular systolic pressure (RVSP) ≥2/3 systemic systolic pressure* Right ventricle (RV) dilatation/septal displacement or RV dysfunction +/- left ventricle (LV) dysfunction* Pre-post ductal SpO2 difference >10% for at least 15 consecutive minutes Oxygenation Index >20** *as found on first ultrasound in first 24 hours after birth; **highest value measured in first 24 hours after birth The following echocardiographic parameters will be collected to objectify these criteria: RV size Pulmonary artery acceleration time (PAAT), right ventricular ejection time (RVET), PAAT:RVET ratio Intraventricular septum configuration LV systolic eccentricity index Mean airway pressure PaO2 FiO2 Preductal+postductal SpO2

Secondary Outcome Measures

Neonatal: mortality before discharge from the tertiary care hospital
Number of patients that died before discharge
Neonatal: presence of 3 or more criteria for pulmonary hypertension or extracorporeal membrane oxygenation within 24 hours after birth
Number of patients with 3 or more criteria or ECMO
Neonatal: number of patients requiring ECMO therapy
Number of patients requiring ECMO therapy
Neonatal: number of days of duration of supplemental oxygen need
Number of days of duration of supplemental oxygen need
Neonatal: number of days of duration of mechanical ventilation
Number of days of duration of mechanical ventilation
Neonatal: duration of admission to the tertiary care hospital
Number of days of admission to the tertiary care hospital
Maternal: number of patients with postpartum haemorrhage
Postpartum haemorrhage is defined as estimated blood loss >1000 mL

Full Information

First Posted
April 14, 2020
Last Updated
September 20, 2023
Sponsor
Erasmus Medical Center
search

1. Study Identification

Unique Protocol Identification Number
NCT04373902
Brief Title
Physiological-based Cord Clamping in Congenital Diaphragmatic Hernia
Acronym
PinC
Official Title
Physiological-based Cord Clamping Versus Immediate Cord Clamping for Infants Born With Congenital Diaphragmatic Hernia: a Multicentre, Randomised Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 11, 2020 (Actual)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Erasmus Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Pulmonary hypertension is a major determinant of postnatal survival in infants with a congenital diaphragmatic hernia (CDH). The current care during the perinatal stabilisation period in infants born with this rare birth defect might contribute to the development of pulmonary hypertension after birth - in particular umbilical cord clamping before lung aeration. An ovine model of diaphragmatic hernia demonstrated that cord clamping after lung aeration, called physiological-based cord clamping (PBCC), avoided the initial high pressures in the lung vasculature while maintaining adequate blood flow, thereby avoiding vascular remodelling and aggravation of pulmonary hypertension. The investigators aim to investigate if the implementation of PBCC in the perinatal stabilisation period of infants born with a CDH could reduce the incidence of pulmonary hypertension in the first 24 hours after birth. The investigators will perform a multicentre, randomised controlled trial in infants with an isolated CDH. Before birth, infants will be randomised to either PBCC or immediate cord clamping, stratified by treatment centre and severity of pulmonary hypoplasia on antenatal ultrasound. For performing PBCC a purpose-designed resuscitation module (the Concord Birth Trolley) will be used.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hernias, Diaphragmatic, Congenital, Hernia; Diaphragm Defect, Congenital, Pulmonary Hypertension
Keywords
Congenital diaphragmatic hernia, Perinatal stabilisation, Resuscitation, Pulmonary hypertension, Birth defect, Physiological-based cord clamping

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Physiological-based cord clamping
Arm Type
Experimental
Arm Description
In PBCC, the Concord will be placed next to the bed of the mother and all equipment will be checked before the second stage of labour has started. The infant will be placed on the platform of the Concord immediately after birth, avoiding any traction or pressure on the cord and avoiding heat loss by radiation heating. The umbilical cord will not be clamped until the infant is considered respiratory stable, which is defined as the presence of a heart rate >100 bpm and preductal oxygen saturation >85%, while using an fraction of inspired oxygen (FiO2) of <0.5. The minimum and maximum times of cord clamping are three and ten minutes after birth, respectively. Oxytocin administration will be postponed until after cord clamping if there are no obstetric concerns. At any time, the attending neonatologist and obstetrician can decide that PBCC should not be performed or be interrupted. In that case, the infant can be placed on the standard resuscitation table for (further) stabilisation.
Arm Title
Immediate cord clamping
Arm Type
No Intervention
Arm Description
In the immediate cord clamping group, the cord will be clamped immediately after birth. The infant will then be transferred to the standard neonatal resuscitation table. After cord clamping, all infants will be managed according to the standardised neonatal management protocol for infants with a CDH, which is a consensus of current clinical guidelines by the CDH EURO consortium.
Intervention Type
Procedure
Intervention Name(s)
Physiological-based cord clamping
Intervention Description
See 'Arm'
Primary Outcome Measure Information:
Title
Number of participants with pulmonary hypertension diagnosed in the first 24 hours after birth.
Description
Pulmonary hypertension is present if at least 2 of the following 4 criteria are present or if the infant requires extracorporeal membrane oxygenation (ECMO) in the first 24 hours after birth: Right ventricular systolic pressure (RVSP) ≥2/3 systemic systolic pressure* Right ventricle (RV) dilatation/septal displacement or RV dysfunction +/- left ventricle (LV) dysfunction* Pre-post ductal SpO2 difference >10% for at least 15 consecutive minutes Oxygenation Index >20** *as found on first ultrasound in first 24 hours after birth; **highest value measured in first 24 hours after birth The following echocardiographic parameters will be collected to objectify these criteria: RV size Pulmonary artery acceleration time (PAAT), right ventricular ejection time (RVET), PAAT:RVET ratio Intraventricular septum configuration LV systolic eccentricity index Mean airway pressure PaO2 FiO2 Preductal+postductal SpO2
Time Frame
First 24 hours after birth
Secondary Outcome Measure Information:
Title
Neonatal: mortality before discharge from the tertiary care hospital
Description
Number of patients that died before discharge
Time Frame
From birth till discharge from the tertiary care hospital, through study completion an average of one year
Title
Neonatal: presence of 3 or more criteria for pulmonary hypertension or extracorporeal membrane oxygenation within 24 hours after birth
Description
Number of patients with 3 or more criteria or ECMO
Time Frame
The first 24 hours after delivery
Title
Neonatal: number of patients requiring ECMO therapy
Description
Number of patients requiring ECMO therapy
Time Frame
From admission to the ICU until the date of death or the date of discharge home, whichever came first
Title
Neonatal: number of days of duration of supplemental oxygen need
Description
Number of days of duration of supplemental oxygen need
Time Frame
From admission to the ICU until the date of discharge to another ward or home, whichever came first,through study completion an average of one year
Title
Neonatal: number of days of duration of mechanical ventilation
Description
Number of days of duration of mechanical ventilation
Time Frame
From admission to the ICU until the date of discharge to another ward or home, whichever came first,through study completion an average of one year
Title
Neonatal: duration of admission to the tertiary care hospital
Description
Number of days of admission to the tertiary care hospital
Time Frame
From admission to the ICU until the date of discharge to another ward or home, whichever came first
Title
Maternal: number of patients with postpartum haemorrhage
Description
Postpartum haemorrhage is defined as estimated blood loss >1000 mL
Time Frame
The first 24 hours after delivery

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Weeks
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Left-sided CDH Isolated CDH: no associated structural or genetic abnormalities that are diagnosed before birth Gestational age at delivery ≥35.0 weeks Parental written informed consent Exclusion Criteria: Right-sided or bilateral CDH Gestational age at delivery <35.0 weeks Maternal contraindications: anterior placenta praevia, placental abruption High urgency caesarean section, with intended interval to delivery <15 min Cases that have been treated during pregnancy with experimental drug therapy aiming to decrease the occurrence of pulmonary hypertension Twin pregnancies in which the infant diagnosed with a CDH is born first Multiple birth >2 (triplets or higher order)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Philip LJ DeKoninck, Dr.
Phone
0031107036614
Email
p.dekoninck@erasmusmc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Emily JJ Horn-Oudshoorn, Drs.
Phone
0031107031334
Email
e.horn-oudshoorn@erasmusmc.nl
Facility Information:
Facility Name
Monash University
City
Melbourne
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
C. Roberts
Facility Name
Medical University Graz
City
Graz
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
B. Urlesberger
Facility Name
University Hospitals leuven
City
Leuven
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A. Debeer
Facility Name
Universitätskrankenhaus Bonn
City
Bonn
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Florian Kipfmueller
Facility Name
Universitätsklinik Mannheim
City
Mannheim
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
T. Schaible
Facility Name
Ospedale Pediatrico Bambino Gesu
City
Rome
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Irma Capolupo
Facility Name
Radboudumc University Medical Center
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Prof. dr. W.P. De Boode
Facility Name
Erasmus MC University Medical Center - Sophia Children's Hospital
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
P.L.J. DeKoninck, Dr.
Phone
0031107036614
Email
p.dekoninck@erasmusmc.nl
Facility Name
Karolinska University Hospital
City
Stockholm
Country
Sweden
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carmen Mesas Burgos

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35304395
Citation
Horn-Oudshoorn EJJ, Knol R, Vermeulen MJ, Te Pas AB, Hooper SB, Cochius-den Otter SCM, Wijnen RMH, Crossley KJ, Rafat N, Schaible T, de Boode WP, Debeer A, Urlesberger B, Roberts CT, Kipfmueller F, Reiss IKM, DeKoninck PLJ. Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC): study protocol for a multicentre, randomised controlled trial. BMJ Open. 2022 Mar 18;12(3):e054808. doi: 10.1136/bmjopen-2021-054808.
Results Reference
derived

Learn more about this trial

Physiological-based Cord Clamping in Congenital Diaphragmatic Hernia

We'll reach out to this number within 24 hrs