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

September 20, 2023 updated by: Philip L.J. DeKoninck, Erasmus Medical Center

Physiological-based Cord Clamping Versus Immediate Cord Clamping for Infants Born With Congenital Diaphragmatic Hernia: a Multicentre, Randomised Controlled Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

140

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
      • Melbourne, Australia
        • Recruiting
        • Monash University
        • Contact:
          • C. Roberts
  • Austria
      • Graz, Austria
        • Recruiting
        • Medical University Graz
        • Contact:
          • B. Urlesberger
  • Belgium
      • Leuven, Belgium
        • Recruiting
        • University Hospitals Leuven
        • Contact:
          • A. Debeer
  • Germany
      • Bonn, Germany
        • Not yet recruiting
        • Universitätskrankenhaus Bonn
        • Contact:
          • Florian Kipfmueller
      • Mannheim, Germany
        • Not yet recruiting
        • Universitätsklinik Mannheim
        • Contact:
          • T. Schaible
  • Italy
      • Rome, Italy
        • Not yet recruiting
        • Ospedale Pediatrico Bambino Gesù
        • Contact:
          • Irma Capolupo
  • Netherlands
      • Nijmegen, Netherlands
        • Recruiting
        • Radboudumc University Medical Center
        • Contact:
          • Prof. dr. W.P. De Boode
      • Rotterdam, Netherlands
        • Recruiting
        • Erasmus MC University Medical Center - Sophia Children's Hospital
        • Contact:
  • Sweden
      • Stockholm, Sweden
        • Not yet recruiting
        • Karolinska University Hospital
        • Contact:
          • Carmen Mesas Burgos

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 months and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Physiological-based cord clamping
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.
Procedure: Physiological-based cord clamping
See 'Arm'
No Intervention: Immediate cord clamping
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with pulmonary hypertension diagnosed in the first 24 hours after birth.
Time Frame: 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:

  1. Right ventricular systolic pressure (RVSP) ≥2/3 systemic systolic pressure*
  2. Right ventricle (RV) dilatation/septal displacement or RV dysfunction +/- left ventricle (LV) dysfunction*
  3. Pre-post ductal SpO2 difference >10% for at least 15 consecutive minutes
  4. 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
First 24 hours after birth

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maternal: number of patients with postpartum haemorrhage
Time Frame: The first 24 hours after delivery
Postpartum haemorrhage is defined as estimated blood loss >1000 mL
The first 24 hours after delivery
Neonatal: mortality before discharge from the tertiary care hospital
Time Frame: From birth till discharge from the tertiary care hospital, through study completion an average of one year
Number of patients that died before discharge
From birth till discharge from the tertiary care hospital, through study completion an average of one year
Neonatal: presence of 3 or more criteria for pulmonary hypertension or extracorporeal membrane oxygenation within 24 hours after birth
Time Frame: The first 24 hours after delivery
Number of patients with 3 or more criteria or ECMO
The first 24 hours after delivery
Neonatal: 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
Number of patients requiring ECMO therapy
From admission to the ICU until the date of death or the date of discharge home, whichever came first
Neonatal: 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
Number of days of duration of supplemental oxygen need
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
Neonatal: 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
Number of days of duration of mechanical ventilation
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
Neonatal: duration 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
Number of days of admission to the tertiary care hospital
From admission to the ICU until the date of discharge to another ward or home, whichever came first

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Erasmus Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 11, 2020

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

July 1, 2024

Study Registration Dates

First Submitted

April 14, 2020

First Submitted That Met QC Criteria

April 30, 2020

First Posted (Actual)

May 5, 2020

Study Record Updates

Last Update Posted (Actual)

September 22, 2023

Last Update Submitted That Met QC Criteria

September 20, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PinC trial
  • NL7853 (Registry Identifier: NTR)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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