Management of the PDA Trial

Study Overview
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Brief Summary
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Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.

Detailed Description
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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).

Official Title
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Management of the Patent Ductus Arteriosus in Premature Infants Trial (PDA Trial)

Conditions
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Infant, Premature, Patent Ductus Arteriosus, Infant, Newborn, Diseases, Patent Ductus Arteriosus After Premature Birth

Intervention / Treatment
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* Other: Active Treatment
* Other: Expectant Management


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 48 Hours
Maximum Age: 21 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Treatment Group<br>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<br>* 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.<br>|
| Active Comparator: Expectant Management Group<br>Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs. | Other: Expectant Management<br>* Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or Bronchopulmonary Dysplasia (BPD) at 36 weeks PMA | Death or BPD. BPD will be defined by the physiologic definition. | birth to 36 week postmenstrual age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at 36 weeks PMA | mortality assessed at 36 week postmenstrual age | birth to 36 week postmenstrual age | 
| Mortality before discharge | mortality assessed prior to hospital discharge | birth to 120 days of life | 
| Bronchopulmonary dysplasia - Physiological Test | BPD defined by the physiologic test of oxygen therapy | birth to 36 week postmenstrual age | 
| Bronchopulmonary dysplasia - NIH Consensus Definition | BPD defined by the NIH consensus definition of moderate or severe | birth to 36 week postmenstrual age | 
| Necrotizing Enterocolitis (NEC) at 36 weeks PMA | Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB | birth to 36 weeks post menstrual age | 
| Retinopathy of Prematurity at 36 weeks PMA | Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug | birth to 36 weeks post menstrual age | 
| Receipt of therapies designed to close the PDA | Defined as ligation or cardiac catheterization | birth to 120 days | 
| Weight at 36 weeks PMA | Weight assessed at 36 weeks post menstrual age | birth to 36 weeks post menstrual age | 
| Height at 36 weeks PMA | Height assessed at 36 weeks post menstrual age | birth to 36 weeks post menstrual age | 
| Head Circumference at 36 weeks PMA | Head Circumference assessed at 36 weeks post menstrual age | birth to 36 weeks post menstrual age |