Management of the PDA Trial
Study Details
Study Description
Brief Summary
Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
This is a pragmatic randomized multicenter, effectiveness study comparing active treatment of a symptomatic patent ductus arteriosus (sPDA) to expectant management. We hypothesize in premature infants with a sPDA, expectant management reduces the incidence proportion of death or BPD by 10% (from 50% to 40%) when compared to active treatment.
Participants with a sPDA allocated to the active treatment arm will receive intravenous administration of indomethacin or ibuprofen (depending on center preference). The decision to ligate will be left to the clinical team. Participants with a sPDA allocated to the expectant management arm will receive supportive care at the clinical team's discretion and will receive indomethacin/ibuprofen or ligation if the infant develops cardiopulmonary compromise. The decision to ligate will be left to the clinical team.
The primary endpoint for the study will be death or BPD (as assessed by the physiologic definition) at 36 weeks postmenstrual age (PMA).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Active Treatment Group Infants assigned to the active treatment group will receive indomethacin or ibuprofen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other. |
Other: Active Treatment
Infants assigned to the active treatment group will receive indomethacin or ibuprofen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other. If the infant receives both, it will be considered a protocol violation.
|
| Active Comparator: Expectant Management Group Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs. |
Other: Expectant Management
Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.
|
Outcome Measures
Primary Outcome Measures
- Death or Bronchopulmonary Dysplasia (BPD) at 36 weeks PMA [birth to 36 week postmenstrual age]
Death or BPD. BPD will be defined by the physiologic definition.
Secondary Outcome Measures
- Mortality at 36 weeks PMA [birth to 36 week postmenstrual age]
mortality assessed at 36 week postmenstrual age
- Mortality before discharge [birth to 120 days of life]
mortality assessed prior to hospital discharge
- Bronchopulmonary dysplasia - Physiological Test [birth to 36 week postmenstrual age]
BPD defined by the physiologic test of oxygen therapy
- Bronchopulmonary dysplasia - NIH Consensus Definition [birth to 36 week postmenstrual age]
BPD defined by the NIH consensus definition of moderate or severe
- Necrotizing Enterocolitis (NEC) at 36 weeks PMA [birth to 36 weeks post menstrual age]
Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB
- Retinopathy of Prematurity at 36 weeks PMA [birth to 36 weeks post menstrual age]
Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug
- Receipt of therapies designed to close the PDA [birth to 120 days]
Defined as ligation or cardiac catheterization
- Weight at 36 weeks PMA [birth to 36 weeks post menstrual age]
Weight assessed at 36 weeks post menstrual age
- Height at 36 weeks PMA [birth to 36 weeks post menstrual age]
Height assessed at 36 weeks post menstrual age
- Head Circumference at 36 weeks PMA [birth to 36 weeks post menstrual age]
Head Circumference assessed at 36 weeks post menstrual age
Other Outcome Measures
- Necrotizing Enterocolitis (NEC) at status (2 years) [26 months corrected age]
Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB
- Retinopathy of Prematurity at status (2 years) [26 months corrected age]
Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug
- Weight at status (2 years) [26 months corrected age]
Weight assessed at status (2 years)
- Height at status (2 years) [26 months corrected age]
Height assessed at status (2 years)
- Head Circumference at status (2 years) [26 months corrected age]
Head Circumference assessed at status (2 years)
- Neurodevelopmental impairment (NDI) at status (2 years) [26 months corrected age]
Severe NDI will be defined by any of the following: a BSID III cognitive score < 70, Gross Motor Functional (GMF) Level of 3-5, blindness (<20/200 vision) or profound hearing loss (inability to understand commands despite amplification); moderate NDI will be defined as a BSID III cognitive score 70-84 and either a GMF level of 2 or a hearing deficit requiring amplification to understand commands or unilateral blindness; mild NDI will be defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMF level 1 or hearing loss not requiring amplification. Normal (no NDI) will be defined by a cognitive score ≥ 85 and absence of any neurosensory deficits.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Postnatal age 48 hours -21 days
-
Infant 22 0/7 to 28 6/7 weeks gestation at birth
-
sPDA, as defined as:
-
Mild, Moderate, or Severe Clinical Criteria with Small or Moderate size PDA on echocardiogram
-
Mild or Moderate Clinical Criteria with Large PDA on echocardiogram
Exclusion Criteria:
-
Cardiopulmonary compromise
-
Known congenital heart disease (besides atrial septal defect or ventricular septal defect)
-
Known pulmonary malformation (e.g. congenital lobar emphysema, congenital pulmonary adenomatous malformation)
-
Any condition which, in the opinion of the investigator, would preclude enrollment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35233 |
| 2 | Stanford University | Palo Alto | California | United States | 94304 |
| 3 | Emory University | Atlanta | Georgia | United States | 30303 |
| 4 | University of Iowa | Iowa City | Iowa | United States | 52242 |
| 5 | University of New Mexico | Albuquerque | New Mexico | United States | 87131 |
| 6 | University of Rochester | Rochester | New York | United States | 14642 |
| 7 | RTI International | Durham | North Carolina | United States | 27705 |
| 8 | Duke University | Durham | North Carolina | United States | 27710 |
| 9 | Cincinnati Children's Medical Center | Cincinnati | Ohio | United States | 45267 |
| 10 | Case Western Reserve University, Rainbow Babies and Children's Hospital | Cleveland | Ohio | United States | 44106 |
| 11 | Research Institute at Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
| 12 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 13 | Brown University - Women and Infants Hospital of Rhode Island | Providence | Rhode Island | United States | 02905 |
| 14 | University of Texas Southwestern Medical Center at Dallas | Dallas | Texas | United States | 75235 |
| 15 | University of Texas Health Science Center at Houston | Houston | Texas | United States | 77030 |
| 16 | University of Utah | Salt Lake City | Utah | United States | 84108 |
Sponsors and Collaborators
- NICHD Neonatal Research Network
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- NICHD-NRN-0059