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

Not Applicable

Recruiting

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

• Registration Number: NCT05547165
• Lead Sponsor: Nationwide Children's Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-08-30
• Study First Submitted QC: 2022-09-15
• Study First Posted: 2022-09-21
• Study Start: 2023-02-21
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-30
• Primary Completion: 2026-02-28
• Study Completion: 2026-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 240

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

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Primary Comparator	Echocardiogram, cardiac	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.
Secondary Intervention	Echocardiogram, cardiac	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.
Primary Comparator	Responsive Management Intervention	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.
Primary Comparator	Percutaneous Patent Ductus Arteriosus Closure (PPC)	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.
Secondary Intervention	Percutaneous Patent Ductus Arteriosus Closure (PPC)	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.

Primary Outcome Measures

Name	Time	Method
Number of days free of ventilatory support requirement (ventilator-free days; VFDs)	30 days post-randomization	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.

Secondary Outcome Measures

Name	Time	Method
Diagnosis of cardiac dysfunction	36 weeks post-menstrual age	A diagnosis of left-ventricular output by echocardiography (ECHO) at 36 weeks post-menstrual age.
Infant/Toddler Sensory Profile (Low Registration Domain)	3 - 4 months of corrected age	Caregiver questionnaire responses to determine if their infant appropriately processes and responds to environmental stimuli, versus missing or taking longer to respond ("Low Registration"). There are 13 items with scores of 13 - 65 possible; scores of 42 - 51 are considered "Typical performance".
Infant/Toddler Sensory Profile (Low Threshold Domain)	3 - 4 months of corrected age	Caregiver questionnaire responses which are the sum of the Sensory Sensitivity and Sensation Avoiding domains). Summed scores of 15 - 85 are possible; summed scores of 64 - 81 are considered "Typical performance".
Total days on mechanical ventilation	4 months corrected age	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 on supplemental oxygen	Randomization through 4 months corrected age	Total number of days the study subject requires supplemental oxygen. The subject may be on either invasive or non-invasive ventilatory support during this time. The subject must be free from supplemental oxygen use for a period of at least 24 hours to interrupt or cease counting.
Abnormal cardiac remodeling	36 weeks post-menstrual age	Finding of left-ventricular end-diastolic volume (LV EDV) \>97% on echocardiography (ECHO) at 36 weeks post-menstrual age.
Need for rescue intervention	Randomization through 4 months corrected age	Recording of incidence of need for study subjects randomized to Responsive Management to undergo Percutaneous Patent Ductus Arteriosus Closure (PPC) due to decline in health status.
Diagnosis of pulmonary hypertension or death	36 weeks post-menstrual age	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.
Time to death	Randomization through 4 months corrected age	A continuous measure, in days, of the time from a study subject's randomization to expiration, if this occurs.
Hammersmith Neonatal Neurological Examination (HNNE)	34 - 36 weeks post-menstrual age	The HNNE is a standardized neurological examination of 34 items to evaluate tone, motor patterns, spontaneous movements, reflexes, visual and auditory attention, and behavior.
Hammersmith Infant Neurological Examination (HINE)	3 - 4 months of corrected age	The HINE is similar to the HNNE, used to assess neurological function at 3 - 24 months of age, including cranial nerve function, movements, reflexes, protective reactions and behavior, and age-dependent evaluation of gross and fine-motor function.
Infant/Toddler Sensory Profile (Sensation Avoiding Domain)	3 - 4 months of corrected age	Caregiver questionnaire responses to determine if their infant avoids sensory stimulation. There are 5 items with scores of 5 - 25 possible; scores of 19 - 25 are considered "Typical performance".
Type and incidence of serious adverse event	3 - 4 months of corrected age	Reporting of type and frequency of any serious adverse event (e.g., potentially life-threatening change in status) that occurs during percutaneous closure procedures, and post-procedurally that may be related to the intervention.
Positive-pressure dependency or death	36 weeks post-menstrual age	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.
Days requiring positive-pressure assisted breathing	Randomization through 4 months corrected age	The sum of days the study subject requires either invasive or non-invasive positive pressure assisted ventilation within a 24 hour calendar day.
General Movements Assessment (GMA)	34 - 36 weeks post-menstrual age	The General Movements Assessment (GMA) is a standardized video-based neurological exam to evaluate the presence of "fidgety" versus "absent fidgety" and "cramped-synchronized" versus "non cramped-synchronized" movement patterns at 34 - 36 weeks post-menstrual age. It is used to assist in the diagnosis of impaired motor neurodevelopment and cerebral palsy.
Infant/Toddler Sensory Profile (Sensory Sensitivity Domain)	3 - 4 months of corrected age	Caregiver questionnaire responses to determine if their infant responds readily to sensory stimulation, without actively avoiding it. There are 12 items with scores of 12 - 60 possible; scores of 45 - 57 are considered "Typical performance)
Type and incidence of any adverse event	3 - 4 months of corrected age	Reporting of type and frequency of any adverse event that occurs during percutaneous closure procedures, and post-procedurally that may be related to the intervention.
Infant/Toddler Sensory Profile (Sensation Seeking Domain)	3 - 4 months of corrected age	Caregiver questionnaire responses to determine if their infant is hyposensitive, seeking additional sensory stimulation. There are 6 items with scores of 6 - 30 possible; scores of 7 - 15 are considered "Typical performance".
Baby Care Questionnaire (BCQ)	3 - 4 months of corrected age	The BCQ is another caregiver-based questionnaire for parental perspectives of an infant's feeding and sleeping habits. It is used as an evaluation of a parent's reliance upon structure / routines and attunement (dependence upon infant's cues).
Mother-Infant Bonding Scale (MIBS)	3 - 4 months of corrected age	The MIBS is an 8-item questionnaire to evaluate a mother's bondedness towards her infant. Responses are scored from 0 to 3 for each item, with a total possible range of 0 - 24. Lower scores indicate more favorable outcomes for mother-infant bondedness, whereas higher scores indicate the potential for difficulties.

Trial Locations

Locations (24)

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Orlando Health; 🇺🇸 Orlando, Florida, United States

Ann and Robert H. Lurie Children's Hospital; 🇺🇸 Chicago, Illinois, United States

Arkansas Children's Hospital; 🇺🇸 Little Rock, Arkansas, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Joe DiMaggio Children's Hospital; 🇺🇸 Hollywood, Florida, United States

Lucille Packard Children's Hospital at Stanford; 🇺🇸 Palo Alto, California, United States

UC Davis Children's Hospital; 🇺🇸 Sacramento, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States

C.S. Mott Children's Hospital; 🇺🇸 Ann Arbor, Michigan, United States

University of Minnesota, Masonic Children's Hospital; 🇺🇸 Minneapolis, Minnesota, United States

St. Louis Children's Hospital; 🇺🇸 Saint Louis, Missouri, United States

Morgan Stanley Children's Hospital of New York-Presbyterian; 🇺🇸 New York, New York, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Le Bonheur Children's Medical Center; 🇺🇸 Memphis, Tennessee, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt; 🇺🇸 Nashville, Tennessee, United States

Medical City Children's Dallas; 🇺🇸 Dallas, Texas, United States

UT Southwestern Children's Medical Center of Dallas; 🇺🇸 Dallas, Texas, United States

Texas Children's; 🇺🇸 Houston, Texas, United States

Seattle Children's; 🇺🇸 Seattle, Washington, United States

Children's Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States