Clinical trial NCT05547165: Percutaneous Intervention Versus Observational Trial of Arterial Ductus in Low Weight Infants
Official title: Percutaneous Intervention Versus Observational Trial of Arterial Ductus in Low Weight Infants
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ductus Arteriosus, Patent
Keywords: PDA
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Abbott
name: University of Pittsburgh
name: University of Bristol
name: Dartmouth College
name: University of Iowa
name: Emory University
name: Cedars-Sinai Medical Center
name: Children's Hospital Los Angeles
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-09-21
Enrollment: 240
Sex: ALL
Minimum age (years): 7
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of days free of ventilatory support requirement (ventilator-free days; VFDs)
timeFrame: 30 days post-randomization
Secondary outcomes:
measure: Positive-pressure dependency or death
timeFrame: 36 weeks post-menstrual age
measure: Diagnosis of pulmonary hypertension or death
timeFrame: 36 weeks post-menstrual age
measure: Total days on mechanical ventilation
timeFrame: 4 months corrected age
measure: Days requiring positive-pressure assisted breathing
timeFrame: Randomization through 4 months corrected age
measure: Days on supplemental oxygen
timeFrame: Randomization through 4 months corrected age
measure: Time to death
timeFrame: Randomization through 4 months corrected age
measure: Diagnosis of cardiac dysfunction
timeFrame: 36 weeks post-menstrual age
measure: Abnormal cardiac remodeling
timeFrame: 36 weeks post-menstrual age
measure: General Movements Assessment (GMA)
timeFrame: 34 - 36 weeks post-menstrual age
measure: Need for rescue intervention
timeFrame: Randomization through 4 months corrected age
measure: Hammersmith Neonatal Neurological Examination (HNNE)
timeFrame: 34 - 36 weeks post-menstrual age
measure: Hammersmith Infant Neurological Examination (HINE)
timeFrame: 3 - 4 months of corrected age
measure: Infant/Toddler Sensory Profile (Low Registration Domain)
timeFrame: 3 - 4 months of corrected age
measure: Infant/Toddler Sensory Profile (Sensation Seeking Domain)
timeFrame: 3 - 4 months of corrected age
measure: Infant/Toddler Sensory Profile (Sensory Sensitivity Domain)
timeFrame: 3 - 4 months of corrected age
measure: Infant/Toddler Sensory Profile (Sensation Avoiding Domain)
timeFrame: 3 - 4 months of corrected age
measure: Infant/Toddler Sensory Profile (Low Threshold Domain)
timeFrame: 3 - 4 months of corrected age
measure: Baby Care Questionnaire (BCQ)
timeFrame: 3 - 4 months of corrected age
measure: Mother-Infant Bonding Scale (MIBS)
timeFrame: 3 - 4 months of corrected age
measure: Type and incidence of any adverse event
timeFrame: 3 - 4 months of corrected age
measure: Type and incidence of serious adverse event
timeFrame: 3 - 4 months of corrected age
Other outcomes:
measure: Determine whether neurodevelopment at 3-4 months CA is mediated by improved neurodevelopmental profiles at 34-36 weeks PMA.
timeFrame: 34-36 weeks post-menstrual age and 3 - 4 months corrected age
measure: Evaluation of effect modifiers on primary and secondary outcomes
timeFrame: Birth to 4 months of corrected age
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Palo Alto
country: United States
facility: Lucille Packard Children's Hospital at Stanford
state: California
city: Sacramento
country: United States
facility: UC Davis Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Hollywood
country: United States
facility: Joe DiMaggio Children's Hospital
state: Florida
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota, Masonic Children's Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: New York
country: United States
facility: Morgan Stanley Children's Hospital of New York-Presbyterian
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Memphis
country: United States
facility: Le Bonheur Children's Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Monroe Carell Jr. Children's Hospital at Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: Medical City Children's Dallas
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Children's Medical Center of Dallas
state: Texas
city: Houston
country: United States
facility: Texas Children's
state: Texas
city: Seattle
country: United States
facility: Seattle Children's
state: Washington
city: Milwaukee
country: United States
facility: Children's Wisconsin
state: Wisconsin
Study officials:
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