Infant, Premature, Patent Ductus Arteriosus, Infant, Newborn, Diseases, Patent Ductus Arteriosus After Premature Birth
Conditions
Brief summary
Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.
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).
Interventions
OTHERActive 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.
OTHERExpectant Management
Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.
Sponsors
NICHD Neonatal Research Network
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
48 Years to 21 Days
Healthy volunteers
No
Inclusion criteria
* Postnatal age 48 hours -21 days * Infant 22 0/7 to 28 6/7 weeks gestation at birth * sPDA, as defined as: 1. Mild, Moderate, or Severe Clinical Criteria with Small or Moderate size PDA on echocardiogram 2. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death or Bronchopulmonary Dysplasia (BPD) at 36 Weeks PMA | Randomization to 36 weeks PMA | A composite outcome for infants who were diagnosed with physiologic bronchopulmonary dysplasia (BPD) or died by 36 weeks postmenstrual age (PMA). Physiologic BPD is determined using existing Neonatal Research Network Generic Database criteria at 36 weeks PMA. Infants alive an in hospital are classified based on respiratory status at 36 weeks PMA or by a room air weaning challenge performed between 36 and 37 weeks PMA. Infants who are transferred or discharged before 36 weeks are classified based on the support they are receiving at that time. Infants who died before 36 weeks PMA are not assessed for BPD. Deaths include all-cause deaths between randomization and 36 weeks PMA. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Participant flow
Pre-assignment details
One infant was randomized but withdrew consent for use of any data. This infant is included in the Period table below, but excluded from all analyses.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 25.6 Weeks |
| Ethnicity (NIH/OMB) Hispanic or Latino | 58 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 368 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 16 Participants |
| Race (NIH/OMB) Black or African American | 175 Participants |
| Race (NIH/OMB) More than one race | 7 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 42 Participants |
| Race (NIH/OMB) White | 120 Participants |
| Sex: Female, Male Female | 120 Participants |
| Sex: Female, Male Male | 123 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 23 / 240 | 10 / 241 |
| other Total, other adverse events | 3 / 240 | 9 / 241 |
| serious Total, serious adverse events | 43 / 240 | 32 / 241 |
Outcome results
None listed