Percutaneous Intervention Versus Observational Trial of Arterial Ductus in Low Weight Infants (PIVOTAL)

Nationwide Children's Hospital

Status: Enrolling

Conditions: Ductus Arteriosus, Patent

Treatments: Device: Percutaneous Patent Ductus Arteriosus Closure (PPC); Combination Product: Responsive Management Intervention; Diagnostic Test: Echocardiogram, cardiac

Study type: Interventional

Funder types: Other; Industry; NIH

Identifiers

NCT05547165

UG3HL161338 (U.S. NIH Grant/Contract)

00002501

Details and patient eligibility

About

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.

Enrollment: 240 estimated patients

Sex: All

Ages: 7 to 32 days old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. EPIs born between 22-weeks+0 days (220/7 wks) and 27-weeks+6 days (276/7 wks) gestation, inclusive
2. Admitted to a study NICU
3. Birth weight ≥700-grams
4. Mechanically ventilated at time of consent and randomization
5. HSPDA ("PDA Score" ≥6) noted on echocardiogram (ECHO)
6. Randomization is able to be performed within 5 days of the qualifying ECHO and when infant is 7-32 days postnatal

Exclusion criteria

Clinical Exclusion Criteria

1. 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;
2. Congenital lung abnormalities, (e.g. restrictive lung disease);
3. Pharyngeal or airway anomalies (tracheal stenosis, choanal atresia);
4. Treatment for acute abdominal process (e.g., necrotizing enterocolitis);
5. Infants with planned surgery;
6. Active infection requiring treatment;
7. Chromosomal defects (e.g., Trisomy 18);
8. Neuromuscular disorders;
9. Infants whose parents have chosen to allow natural death (do not resuscitate order) or for whom limitation of intensive care treatment is being considered (e.g. severe intraventricular hemorrhage)
10. Physician deems that the infant would not be a Percutaneous PDA Closure candidate due to clinical instability; however, if the infant's clinical status improves before 30-days postnatal and all inclusion criteria are still met, then the infant may be enrolled.

ECHO-based Exclusion Criteria

1. Pulmonary hypertension (defined by ductal right to left shunting for >33% of the cardiac cycle) in which early PDA closure may increase right ventricular afterload and compromise pulmonary and systemic blood flow;
2. Evidence of cardiac thrombus that might interfere with device placement;
3. PDA diameter larger than 4 mm at the narrowest portion (consistent with FDA-approved instructions for Piccolo™ device use).
4. PDA length smaller than 3 mm (consistent with FDA-approved instructions for Piccolo™ device use).
5. PDA that does not meet inclusion requirements ("PDA Score" <6).* * If a potential participant is found to have a PDA meeting eligibility requirements on a subsequent ECHO during the required period of 7 - 30 postnatal days of age, they may then be declared eligible to participate and enrolled, provided all other inclusion criteria are met and exclusion criteria are not met.

Other Exclusion Criteria

1. Parents or legal guardian do not speak English or Spanish

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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240 participants in 2 patient groups

Primary Comparator

Active Comparator group

Description:

Interventional groups that subject will be randomly assigned to include Percutaneous Patent Ductus Arteriosus Closure (PPC) or Responsive Management. Those assigned to PPC will undergo active intervention to close a hemodynamically significant patent ductus arteriosus (HSPDA) whereas those assigned to Responsive Management will be treated to manage the symptoms of the HSPDA and permit natural closure over time.

Treatment:

Diagnostic Test: Echocardiogram, cardiac

Combination Product: Responsive Management Intervention

Device: Percutaneous Patent Ductus Arteriosus Closure (PPC)

Secondary Intervention

Other group

Description:

Sub-group of patients initially randomized to Responsive Management who may suffer a decline in health status that can be attributed to the presence of a hemodynamically significant patent ductus arteriosus (HSPDA). These patients, upon meeting pre-specified clinical criteria, will undergo active treatment via Percutaneous Patent Ductus Arteriosus Closure (PPC) as in the active comparator arm.

Treatment:

Diagnostic Test: Echocardiogram, cardiac

Device: Percutaneous Patent Ductus Arteriosus Closure (PPC)