Patent Ductus Arteriosus is a developmental condition commonly observed among preterm infants. It is a condition where the opening between the two major blood vessels leading from the heart fail to close after birth. In the womb, the opening (ductus arteriosus) is the normal part of the circulatory system of the baby, but is expected to close at full term birth. If the opening is tiny, the condition can be self-limiting. If not, medications/surgery are options for treatment.
There are two ways to treat patent ductus arteriosus - one is through closure of the opening with an FDA approved device called PICCOLO, the other is through supportive management (medications). No randomized controlled trials have been done previously to see if one of better than the other. Through our PIVOTAL study, the investigators aim to determine is one is indeed better than the other - if it is found that the percutaneous closure with PICCOLO is better, then it would immediately lead to a new standard of care. If not, then the investigators avoid an invasive costly procedure going forward.
EPIs born between 22-weeks+0 days (220/7 wks) and 27-weeks+6 days (276/7 wks) gestation, inclusive
Admitted to a study NICU
Birth weight ≥700-grams
Mechanically ventilated at time of consent and randomization
Life-threatening congenital defects (including congenital heart disease such as aortic coarctation or pulmonary artery stenosis). PDA and small atrial/ventricular septal defects are permitted;
Congenital lung abnormalities, (e.g. restrictive lung disease);
Pharyngeal or airway anomalies (tracheal stenosis, choanal atresia);
Treatment for acute abdominal process (e.g., necrotizing enterocolitis);
Parallel
Percutaneous Patent Ductus Arteriosus Closure (PPC)
DeviceInfants in this group will undergo catheter-based PPC closure ≤48 hours following randomization and within 7-days of qualifying ECHO. All participants assigned to PPC will receive the Amplatzer Piccolo™ Occluder which will be implanted within the duct (intraductal placement). The Piccolo™ occluder is approved by the US FDA for this purpose.
Responsive Management Intervention
Combination productInterventional PDA-closure, including PPC or surgical ligation and post-randomization pharmacologic (NSAID or acetaminophen) (enteral or intravenous) PDA treatment, are not allowed unless secondary treatment thresholds (see below) are met. Healthcare decisions for Responsive Management will be made at the discretion of the treatment team, while the infant is carefully monitored for any decline in status that may be attributed to the presence of PDA, in which case, Secondary Intervention (described below) may be considered. Despite widespread acceptance of responsive PDA management, no consensus definition exists. The following Responsive Management interventions are permitted but not required per clinician discretion: 1) fluid restriction between 120-140 mL/kg/day; 2) diuretics (per local practice); 3) increases in positive end-expiratory pressure (PEEP).
Echocardiogram, cardiac
Diagnostic testAn echocardiogram, also known as "ECHO", is an ultrasound image of the heart. Echocardiography is a common test used for the diagnosis and management of cardiac diseases or conditions.
Number of days free of ventilatory support requirement (ventilator-free days; VFDs)
Ventilator free days (VFDs) are defined as the number of days that a subject is alive and free from mechanical ventilatory support. VFDs are an established respiratory outcome measure in pediatric clinical trials, and are a strong predictor of short-term and longer-term oucomes, including length of neonatal intensive care unit (NICU) stay, morbidities, and mortality.
Positive-pressure dependency or death
A composite outcome measure (yes/no), positive pressure dependency at 36 weeks post-menstrual age (PMA) is an indicator of chronic lung disease (CLD), the most common and serious respiratory complication of prematurity. Both invasive and non-invasive positive pressure ventilation at 36 weeks PMA is associated with long-term respiratory and neurodevelopmental impairment.
Diagnosis of pulmonary hypertension or death
A compositve binary outcome measure (yes/no), diagnosis of pulmonary hypertension will be determined by cardiac echocardiogram at 36 weeks post-menstrual age. Diagnosis of pulmonary hypertension is an indicator of increased pulmonary vasculature resistance, a marker for increased morbidity and mortality among infants with chronic lung disease.
Total days on mechanical ventilation
The total number of days (continuous variable) a study subject requires any use of invasive mechanical ventilatory support within a 24-hour calendar day.
Days requiring positive-pressure assisted breathing
The sum of days the study subject requires either invasive or non-invasive positive pressure assisted ventilation within a 24 hour calendar day.
Determine whether neurodevelopment at 3-4 months CA is mediated by improved neurodevelopmental profiles at 34-36 weeks PMA.
Analysis of HNNE / HINE scores to determine if neurodevelopmental evaluation scores conducted at 34 - 36 weeks post-menstrual age mediate outcomes at 3 - 4 months corrected age
Evaluation of effect modifiers on primary and secondary outcomes
Examination of the homogeneity of the effect of HSPDA on the primary and secondary outcomes will be carried out in statistical analyses using stratification variables (e.g., gender, gestational age, etc.) and characteristics not balanced through random assignment, if any such imbalances are found.
Click on the lead sponsor to view all of their trials.
Nationwide Children's Hospital
Lead sponsor
National Institutes of Health (NIH)
Collaborator
Abbott
Collaborator
University of Pittsburgh
Collaborator
University of Bristol
Collaborator
Dartmouth College
Collaborator
University of Iowa
Collaborator
Emory University
Collaborator
Cedars-Sinai Medical Center
Collaborator
Children's Hospital Los Angeles
Collaborator
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
