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| ID | Type | Description | Link |
|---|---|---|---|
| K23HD084727 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DING intervention | Experimental | Delayed Cord Clamping |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DING | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Arterial Potential of Hydrogen (pH) in Arterial Blood | Arterial pH on first blood gas | Approximately 1 hour of life |
| Mean Partial Pressure of O2 in Arterial Blood (PaO2) | Arterial PaO2 on first blood gas |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Elizabeth Foglia, MD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25825963 | Background | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | DING Intervention | Delayed Cord Clamping 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | DING Intervention | Delayed Cord Clamping 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 | Posted | Count of Participants | Participants | 3 minutes of life |
|
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24 hours following allocation to the DING intervention.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | DING Intervention | Delayed Cord Clamping 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Elizabeth Foglia | Childrens Hospital of Philadelphia | 215-590-1653 | foglia@email.chop.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 5, 2018 | Oct 25, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D065630 | Hernias, Diaphragmatic, Congenital |
| ID | Term |
|---|---|
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D006548 | Hernia, Diaphragmatic |
| D000082122 | Internal Hernia |
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Unblinded single-arm pilot interventional trial. All enrolled infants will receive the DING intervention (Delayed cord clamping for INtubation and Gentle ventilation)
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| Approximately 1 hour of life |
| Oxygenation Index (OI) | Oxygenation index [OI] with first obtained blood gas | First obtained blood gas |
| Proportion of Infants Who Require Vasopressors | Proportion of infants who require vasopressors in first 48 hours of life | First 48 hours of life |
| Presence of Severe Pulmonary Hypertension | Presence of severe pulmonary hypertension on first echocardiogram | Approximately 24 hours of life |
| 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 |
| Mortality in First 7 Days of Life | Proportion of infants with mortality in the first 7 days of life | First 7 days of life |
| weeks |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
|
| Secondary | Mean Arterial Potential of Hydrogen (pH) in Arterial Blood | Arterial pH on first blood gas | 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results. | Posted | Mean | Standard Deviation | pH | Approximately 1 hour of life |
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| Secondary | Mean Partial Pressure of O2 in Arterial Blood (PaO2) | Arterial PaO2 on first blood gas | 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results. | Posted | Median | Inter-Quartile Range | PaO2 | Approximately 1 hour of life |
|
|
|
| Secondary | Oxygenation Index (OI) | Oxygenation index [OI] with first obtained blood gas | 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results. | Posted | Median | Inter-Quartile Range | oxygenation index | First obtained blood gas |
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|
|
| Secondary | Proportion of Infants Who Require Vasopressors | Proportion of infants who require vasopressors in first 48 hours of life | 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results. | Posted | Count of Participants | Participants | First 48 hours of life |
|
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|
| Secondary | Presence of Severe Pulmonary Hypertension | Presence of severe pulmonary hypertension on first echocardiogram | 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results. 1 trial participant was supported with ECMO when the echocardiogram was obtained and therefore was not assessed. | Posted | Count of Participants | Participants | Approximately 24 hours of life |
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|
| Secondary | Proportion of Infants Who Require Extracorporeal Membrane Oxygenation (ECMO) Treatment | Proportion of infants who require ECMO treatment in first 7 days of life | 1 of the 20 infants randomized to the intervention was diagnosis with a second major anomaly postnatally and was not included in the secondary outcome results. | Posted | Count of Participants | Participants | 7 days of life |
|
|
|
| Secondary | Mortality in First 7 Days of Life | Proportion of infants with mortality in the first 7 days of life | Posted | Count of Participants | Participants | First 7 days of life |
|
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| 0 |
| 20 |
| 3 |
| 20 |
| 0 |
| 20 |
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| D006547 | Hernia |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |