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

NCT05547165 | Recruiting DMC FDA Device

• 2 other identifiers: 00002501UG3HL161338
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 24

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.

Conditions

Ductus Arteriosus, Patent

Keywords

PDA

Outcome Measures

Primary Outcomes (1)

• 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.

  30 days post-randomization

Secondary Outcomes (21)

• Positive-pressure dependency or death

  36 weeks post-menstrual age

• Diagnosis of pulmonary hypertension or death

  36 weeks post-menstrual age

• Total days on mechanical ventilation

  4 months corrected age

• Days requiring positive-pressure assisted breathing

  Randomization through 4 months corrected age

• Days on supplemental oxygen

  Randomization through 4 months corrected age

Other Outcomes (2)

• Determine whether neurodevelopment at 3-4 months CA is mediated by improved neurodevelopmental profiles at 34-36 weeks PMA.

  34-36 weeks post-menstrual age and 3 - 4 months corrected age

• Evaluation of effect modifiers on primary and secondary outcomes

  Birth to 4 months of corrected age

Study Arms (2)

Primary Comparator

ACTIVE 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); Combination Product: Responsive Management Intervention; Diagnostic Test: Echocardiogram, cardiac

Secondary Intervention

OTHER

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); Diagnostic Test: Echocardiogram, cardiac

Interventions

Percutaneous Patent Ductus Arteriosus Closure (PPC) DEVICE

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.

Primary Comparator; Secondary Intervention

Responsive Management Intervention COMBINATION_PRODUCT

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).

Primary Comparator

Echocardiogram, cardiac DIAGNOSTIC_TEST

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.

Primary Comparator; Secondary Intervention

Eligibility Criteria

• Age: 7 Days - 32 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• HSPDA ("PDA Score" ≥6) noted on echocardiogram (ECHO)
• Randomization is able to be performed within 5 days of the qualifying ECHO and when infant is 7-32 days postnatal

You may not qualify if:

• 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);
• Infants with planned surgery;
• Active infection requiring treatment;
• Chromosomal defects (e.g., Trisomy 18);
• Neuromuscular disorders;
• 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)
• 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;
• Evidence of cardiac thrombus that might interfere with device placement;
• PDA diameter larger than 4 mm at the narrowest portion (consistent with FDA-approved instructions for Piccolo™ device use).
• PDA length smaller than 3 mm (consistent with FDA-approved instructions for Piccolo™ device use).
• \. Parents or legal guardian do not speak English or Spanish

Sponsors & Collaborators

• Nationwide Children's Hospital: lead
• 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

Study Sites (24)

University of Alabama

Birmingham, Alabama, 35294, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

WITHDRAWN

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Lucille Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

WITHDRAWN

UC Davis Children's Hospital

Sacramento, California, 95817, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

WITHDRAWN

Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

RECRUITING

Orlando Health

Orlando, Florida, 32806, United States

RECRUITING

Ann and Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

WITHDRAWN

University of Minnesota, Masonic Children's Hospital

Minneapolis, Minnesota, 55455, United States

WITHDRAWN

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

RECRUITING

Morgan Stanley Children's Hospital of New York-Presbyterian

New York, New York, 10032, United States

WITHDRAWN

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

WITHDRAWN

Le Bonheur Children's Medical Center

Memphis, Tennessee, 38103, United States

RECRUITING

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

WITHDRAWN

Medical City Children's Dallas

Dallas, Texas, 75230, United States

RECRUITING

UT Southwestern Children's Medical Center of Dallas

Dallas, Texas, 75235, United States

RECRUITING

Texas Children's

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's

Seattle, Washington, 98105, United States

RECRUITING

Children's Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Related Publications (28)

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MeSH Terms

Conditions

Ductus Arteriosus, Patent

Interventions

Echocardiography

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular

Central Study Contacts

Carl H Backes

CONTACT

16143556729; carl.backes@nationwidechildrens.org

Jonathan Slaughter

CONTACT

16143556643; jonathan.slaughter@nationwidechildrens.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics, Departments of Neonatology and Cardiology

Study Record Dates

• First Submitted: August 30, 2022
• First Posted: September 21, 2022
• Study Start: February 21, 2023
• Primary Completion: February 28, 2026
• Study Completion: February 28, 2026
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (24)