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Purpose

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.

Condition

Eligibility

Eligible Ages
Between 7 Days and 32 Days
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Primary Comparator 		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.
  • Device: Percutaneous Patent Ductus Arteriosus Closure (PPC)
    Infants 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.
  • Combination Product: Responsive Management Intervention
    Interventional 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).
  • Diagnostic Test: Echocardiogram, cardiac
    An 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.
Other
Secondary Intervention 		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.
  • Device: Percutaneous Patent Ductus Arteriosus Closure (PPC)
    Infants 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.
  • Diagnostic Test: Echocardiogram, cardiac
    An 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.

Recruiting Locations

Arkansas Children's Hospital
Little Rock, Arkansas 72202
Contact:
Megha Sharma, MD
MSharma@uams.edu

UC Davis Children's Hospital
Sacramento, California 95817
Contact:
Frank Ing, MD
ffing@ucdavis.edu

Children's Hospital Colorado
Aurora, Colorado 80045
Contact:
Theresa Grover, MD
Theresa.Grover@childrenscolorado.org

Joe DiMaggio Children's Hospital
Hollywood, Florida 33021
Contact:
Peter Guyton, MD
PGuyon@mhs.net

Orlando Health
Orlando, Florida 32806
Contact:
Michael McMahan, MD
Michael.McMahan@orlandohealth.com

Ann and Robert H. Lurie Children's Hospital
Chicago, Illinois 60611
Contact:
Nicolas Porta, MD
nporta@luriechildrens.org

University of Minnesota, Masonic Children's Hospital
Minneapolis, Minnesota 55455
Contact:
Gurumurthy Hiremath, MD
hiremath@umn.edu

St. Louis Children's Hospital
Saint Louis, Missouri 63110
Contact:
Daisuke Kobayashi, MD
daisuke@wustl.edu

Nationwide Children's Hospital
Columbus, Ohio 43205
Contact:
Jonathan Slaughter, MD
Jonathan.Slaughter@nationwidechildrens.org

Medical City Children's Dallas
Dallas, Texas 75230
Contact:
Vivian Dimas, MD
vivian.dimas@hcahealthcare.com

More Details

NCT ID
NCT05547165
Status
Recruiting
Sponsor
Nationwide Children's Hospital

Study Contact

Carl H Backes
16143556729
carl.backes@nationwidechildrens.org

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.