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

Nationwide Children's Hospital240 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

240

Conditions

Ductus Arteriosus, Patent

Interventions

Responsive Management InterventionCOMBINATION_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).

Eligibility

Sex: ALLMin age: 7 DaysMax age: 32 Days

Medical Language ↔ Plain English

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

Locations (24)

University of Alabama

Birmingham, Alabama, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, United States

RECRUITING

Children's Hospital Los Angeles

Los Angeles, California, United States

WITHDRAWN

Cedars-Sinai Medical Center

Los Angeles, California, United States

RECRUITING

Lucille Packard Children's Hospital at Stanford

Palo Alto, California, United States

WITHDRAWN

UC Davis Children's Hospital

Sacramento, California, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

WITHDRAWN

Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

RECRUITING

Orlando Health

Orlando, Florida, United States

RECRUITING

Ann and Robert H. Lurie Children's Hospital

Chicago, Illinois, United States

RECRUITING

...and 14 more locations

Outcomes

Primary Outcomes

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.

Time frame: 30 days post-randomization

Secondary Outcomes

Positive-pressure dependency or death

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.

Time frame: 36 weeks post-menstrual age

Diagnosis of pulmonary hypertension or death

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 frame: 36 weeks post-menstrual age

Total days on mechanical ventilation

The total number of days (continuous variable) a study subject requires any use of invasive mechanical ventilatory support within a 24-hour calendar day.

Time frame: 4 months corrected age

Days requiring positive-pressure assisted breathing

The sum of days the study subject requires either invasive or non-invasive positive pressure assisted ventilation within a 24 hour calendar day.

Time frame: Randomization through 4 months corrected age

Days on supplemental oxygen

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.

Time frame: Randomization through 4 months corrected age

Time to death

A continuous measure, in days, of the time from a study subject's randomization to expiration, if this occurs.

Time frame: Randomization through 4 months corrected age

Diagnosis of cardiac dysfunction

A diagnosis of left-ventricular output by echocardiography (ECHO) at 36 weeks post-menstrual age.

Time frame: 36 weeks post-menstrual age

Abnormal cardiac remodeling

Finding of left-ventricular end-diastolic volume (LV EDV) \>97% on echocardiography (ECHO) at 36 weeks post-menstrual age.

Time frame: 36 weeks post-menstrual age

General Movements Assessment (GMA)

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.

Time frame: 34 - 36 weeks post-menstrual age

Need for rescue intervention

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.

Time frame: Randomization through 4 months corrected age

Hammersmith Neonatal Neurological Examination (HNNE)

The HNNE is a standardized neurological examination of 34 items to evaluate tone, motor patterns, spontaneous movements, reflexes, visual and auditory attention, and behavior.

Time frame: 34 - 36 weeks post-menstrual age

Hammersmith Infant Neurological Examination (HINE)

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.