Clinical trial NCT03314233: Delayed Cord Clamping for Congenital Diaphragmatic Hernia
Official title: Delayed Cord Clamping for Intubation and Gentle Ventilation in Infants With Congenital Diaphragmatic Hernia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Congenital Diaphragmatic Hernia
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2017-10-19
Enrollment: 21
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Unblinded single-arm pilot interventional trial. All enrolled infants will receive the DING intervention (Delayed cord clamping for INtubation and Gentle ventilation)
Primary purpose: OTHER

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of Infants Who Are Intubated Prior to Umbilical Cord Clamping
timeFrame: 3 minutes of life
Secondary outcomes:
measure: Mean Arterial Potential of Hydrogen (pH) in Arterial Blood
timeFrame: Approximately 1 hour of life
measure: Mean Partial Pressure of O2 in Arterial Blood (PaO2)
timeFrame: Approximately 1 hour of life
measure: Oxygenation Index (OI)
timeFrame: First obtained blood gas
measure: Proportion of Infants Who Require Vasopressors
timeFrame: First 48 hours of life
measure: Presence of Severe Pulmonary Hypertension
timeFrame: Approximately 24 hours of life
measure: Proportion of Infants Who Require Extracorporeal Membrane Oxygenation (ECMO) Treatment
timeFrame: 7 days of life
measure: Mortality in First 7 Days of Life
timeFrame: First 7 days of life
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Elizabeth Foglia, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.