Delayed Cord Clamping for Congenital Diaphragmatic Hernia

Congenital Diaphragmatic Hernia Clinical Trial

— DING  

Official title:

Delayed Cord Clamping for Intubation and Gentle Ventilation in Infants With Congenital Diaphragmatic Hernia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03314233
• Other study ID #: 17-014125
• Secondary ID: K23HD084727
• Status: Completed
• Phase: N/A
• Start date: October 12, 2017
• Est. completion date: October 9, 2018

Study information

• Verified date: January 2020
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Congenital diaphragmatic hernia (CDH) is a congenital anomaly associated with a high risk of mortality and need for life-saving interventions such as extracorporeal membrane oxygenation (ECMO), nitric oxide, and vasopressor support. Although infants with CDH experience significant morbidity and mortality starting immediately after birth, high quality evidence informing delivery room resuscitation in this population is lacking.

Infants with CDH are at risk for pulmonary hypoplasia and pulmonary hypertension and often experience hypoxemia and acidosis during neonatal transition. The standard approach to DR resuscitation is immediate umbilical cord clamping (UCC) followed by intubation and mechanical ventilation. Animal models suggest that achieving lung aeration prior to UCC results in improved pulmonary blood flow and cardiac function compared with immediate UCC before lung aeration is established. Trials of preterm infants demonstrated that initiating respiratory support prior to UCC is safe and feasible. Because infants with CDH are at high risk for pulmonary hypertension and systemic hypotension, they may benefit from the hemodynamic effects of lung aeration before UCC, namely increased pulmonary blood flow, decreased pulmonary vascular resistance, and improved cardiac output. To date, this approach has not been studied in infants with CDH.

Description:

Congenital diaphragmatic hernia (CDH) is a congenital anomaly associated with a high risk of mortality (29%) and need for life-saving interventions such as ECMO (33%), nitric oxide (62%), and vasopressor support (73%).1 Although infants with CDH experience significant morbidity and mortality starting immediately after birth, high quality evidence informing delivery room resuscitation in this population is lacking.

Infants with CDH are at risk for pulmonary hypoplasia and pulmonary hypertension and often experience hypoxemia and acidosis during neonatal transition. The standard approach to delivery room (DR) resuscitation is immediate UCC followed by intubation and mechanical ventilation. The goals of this strategy are to immediately recruit and aerate the lung for gas exchange and oxygenation, while simultaneously avoiding gaseous distention of the thoracic gastrointestinal contents.

Animal models suggest that achieving lung aeration prior to UCC results in improved pulmonary blood flow and cardiac function compared with immediate UCC before lung aeration is established. Trials of preterm infants demonstrated that initiating respiratory support prior to UCC is safe and feasible. Because infants with CDH are at high risk for pulmonary hypertension and systemic hypotension, they may benefit from the hemodynamic effects of lung aeration before UCC, namely increased pulmonary blood flow, decreased pulmonary vascular resistance, and improved cardiac output.

The investigators hypothesize that a sequence of intubation, gentle ventilation, and then umbilical cord clamping will result in improved cardiovascular transition after birth in infants with CDH. To date, this approach has not been studied in infants with CDH. The DING trial will assess the feasibility and safety of this intervention in infants with CDH.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: October 9, 2018
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 1 Day

Eligibility

Inclusion Criteria:

1. Antenatal diagnosis of CDH, with care in the Center for Fetal Treatment

2. Gestational age = 36 weeks at birth

Exclusion Criteria:

1. Multiple gestation

2. Major anomalies or aneuploidy

3. Enrolled in fetal endoluminal tracheal occlusion (FETO) trial

4. Palliative care planned or considered

5. Maternal diagnosis placenta previa, accreta, or abruption

6. Maternal diagnosis pre-eclampsia requiring Magnesium sulfate therapy at time of delivery

7. Obstetrics (OB) or Neonatal provider concerns for the clinical care of the mother or infant, or study team not available

Related Conditions & MeSH terms

• Congenital Diaphragmatic Hernia
• Hernia
• Hernia, Diaphragmatic
• Hernias, Diaphragmatic, Congenital

Intervention

Procedure:
• DING
Immediately after birth, the infant will be placed on a Lifestart trolley with an intact umbilical cord, intubated, and ventilated with the Children's Hospital of Philadelphia (CHOP) "gentle ventilation" protocol.

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Grover TR, Murthy K, Brozanski B, Gien J, Rintoul N, Keene S, Najaf T, Chicoine L, Porta N, Zaniletti I, Pallotto EK; Children's Hospitals Neonatal Consortium. Short-term outcomes and medical and surgical interventions in infants with congenital diaphragmatic hernia. Am J Perinatol. 2015 Sep;32(11):1038-44. doi: 10.1055/s-0035-1548729. Epub 2015 Mar 31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Infants Who Are Intubated Prior to Umbilical Cord Clamping	Infants who are intubated and have ventilation initiated prior to umbilical cord clamping	3 minutes of life
Secondary	Mean Arterial Potential of Hydrogen (pH) in Arterial Blood	Arterial pH on first blood gas	Approximately 1 hour of life
Secondary	Mean Partial Pressure of O2 in Arterial Blood (PaO2)	Arterial PaO2 on first blood gas	Approximately 1 hour of life
Secondary	Oxygenation Index (OI)	Oxygenation index [OI] with first obtained blood gas	First obtained blood gas
Secondary	Proportion of Infants Who Require Vasopressors	Proportion of infants who require vasopressors in first 48 hours of life	First 48 hours of life
Secondary	Presence of Severe Pulmonary Hypertension	Presence of severe pulmonary hypertension on first echocardiogram	Approximately 24 hours of life
Secondary	Proportion of Infants Who Require Extracorporeal Membrane Oxygenation (ECMO) Treatment	Proportion of infants who require ECMO treatment in first 7 days of life	7 days of life
Secondary	Mortality in First 7 Days of Life	Proportion of infants with mortality in the first 7 days of life	First 7 days of life