Early Prediction of Spontaneous Patent Ductus Arteriosus (PDA) Closure and PDA-Associated Outcomes

Bronchopulmonary Dysplasia Clinical Trial

Official title:

Early Prediction of Spontaneous Patent Ductus Arteriosus (PDA) Closure and PDA-Associated Outcomes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03782610
• Other study ID #: 1800684
• Secondary ID: 1R01HL145032
• Status: Active, not recruiting
• Start date: April 1, 2019
• Est. completion date: June 2026

Study information

• Verified date: November 2023
• Source: Nationwide Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Patent ductus arteriosus (PDA), very common in preterm infants, is the delayed closure of a fetal blood vessel that limits blood flow through the lungs. PDA is associated with mortality and harmful long term outcomes including chronic lung disease and neurodevelopmental delay. Although, treatments to close PDA likely benefit some infants, widespread routine treatment of all preterm infants with PDA may not improve important outcomes. Left untreated, most PDAs close spontaneously. Thus, PDA treatment is increasingly controversial and varies markedly between hospitals and individual providers. The relevant and still unanswered clinical question is not whether to treat all preterm infants with PDA, but whom to treat and when. Treatment detriments may outweigh benefits, since all forms of deliberate PDA closure have potential adverse effects, especially in infants destined for early, spontaneous PDA closure. Unfortunately, clinicians cannot currently predict in the 1st month which infants are at highest risk for persistent PDA, and which combination of clinical risk factors, echocardiographic (echo) measurements, and serum biomarkers may best predict PDA-associated harm. The American Academy of Pediatrics has acknowledged early identification of infants at high-risk from PDA as a key research goal for informing future PDA-treatment effectiveness trials.

Our objective is to use a prospective cohort of untreated infants with PDA to predict spontaneous ductal closure timing and identify echo measurements and biomarkers that are present in the 1st postnatal month and associated with long-term impairment. Our central hypothesis is that these risk factors can be determined to inform appropriate clinical treatments when necessary. Clinical, serum and urine biomarkers (BNP, NTpBNP, NGAL, H-FABP), and echo variables sequentially collected during each of the first 4 postnatal weeks will be examined. In addition myocardial deformation imaging (MDI) and tissue Doppler imaging (TDI), innovative echo methods, will facilitate the quantitative evaluation of myocardial performance. Aim 1 will estimate the probability of spontaneous PDA closure and predict the timing of ductal closure using echo, biomarker, and clinical predictors. Aim 2 will specify which echo predictors and biomarkers are associated with mortality and severity of respiratory illness at 36-weeks PMA. Aim 3 will identify which echo predictors and biomarkers are associated with 22- to 26-month neurodevelopment. All models will be validated in a separate cohort. This project will significantly contribute to clinical outcomes and PDA management by reducing unnecessary and harmful overtreatment of infants with a high probability of early spontaneous PDA closure, and will permit the development of outcomes-focused trials to examine the effectiveness of PDA closure in those "high-risk" infants most likely to receive benefit.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 675
• Est. completion date: June 2026
• Est. primary completion date: March 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 72 Hours

Eligibility

Inclusion Criteria:

• Born between 23-weeks + 0 days (23_0/7 wks) and 29-weeks + 6 days (29_6/7 wks) gestation, inclusive

• Admitted to a study neonatal intensive care unit (NICU) within 72-hours of birth

• PDA noted on initial screening echo at <72 postnatal hours

Exclusion Criteria:

• Life-threatening congenital abnormalities, including congenital heart disease (other than PDA or small atrial septal defects/patent foramen ovale/muscular VSD)

• Parents have chosen to allow natural death (placed a do not resuscitate order)

Related Conditions & MeSH terms

• Bronchopulmonary Dysplasia
• Ductus Arteriosus, Patent
• Neurodevelopmental Abnormality
• Patent Ductus Arteriosus
• Preterm Infant

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital Main Campus Neonatal Intensive Care Unit	Columbus	Ohio
United States	Nationwide Children's Hospital Neonatal Intensive Care Unit at OhioHealth Grant Medical Center	Columbus	Ohio
United States	Nationwide Children's Neonatal Intensive Care Unit at OhioHealth Riverside Methodist Hospital	Columbus	Ohio
United States	Nationwide Children's Neonatal Intensive Care Unit at The Ohio State University Wexner Medical Center	Columbus	Ohio

Sponsors (5)

Lead Sponsor	Collaborator
Nationwide Children's Hospital	Mount Carmel Health System, National Heart, Lung, and Blood Institute (NHLBI), Ohio State University, OhioHealth

Country where clinical trial is conducted

United States, 

References & Publications (3)

Benitz WE; Committee on Fetus and Newborn, American Academy of Pediatrics. Patent Ductus Arteriosus in Preterm Infants. Pediatrics. 2016 Jan;137(1). doi: 10.1542/peds.2015-3730. Epub 2015 Dec 15. — View Citation

Pavlek LR, Slaughter JL, Berman DP, Backes CH. Catheter-based closure of the patent ductus arteriosus in lower weight infants. Semin Perinatol. 2018 Jun;42(4):262-268. doi: 10.1053/j.semperi.2018.05.009. Epub 2018 Jun 13. — View Citation

Slaughter JL, Reagan PB, Newman TB, Klebanoff MA. Comparative Effectiveness of Nonsteroidal Anti-inflammatory Drug Treatment vs No Treatment for Patent Ductus Arteriosus in Preterm Infants. JAMA Pediatr. 2017 Mar 6;171(3):e164354. doi: 10.1001/jamapediatrics.2016.4354. Epub 2017 Mar 6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Normal cardiac function at 36-weeks PMA (binary)	No functional abnormalities identified on the 36-week echocardiogram, as read by the study cardiologist	Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	Quantitative myocardial deformation imaging (MDI) at 36-weeks PMA (continuous)		Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	Quantitative tissue Doppler imaging (TDI) at 36-weeks PMA (continuous)		Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	Pulmonary Hypertension at 36-weeks PMA (binary)	Pulmonary hypertension noted on the 36-week echocardiogram, as read by the study cardiologist	Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	Normal left atrial size at 36-weeks PMA (binary)	No left atrial enlargement identified on the 36-week echocardiogram, as read by the study cardiologist	Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	Normal left ventricular size at 36-weeks PMA (binary)	No left ventricular enlargement identified on the 36-week echocardiogram, as read by the study cardiologist	Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	Normal right ventricular size at 36-weeks PMA (binary)	No right ventricular enlargement identified on the 36-week echocardiogram, as read by the study cardiologist	Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	Oxygen Dependency (Moderate BPD) (binary)		Recorded at 36-weeks PMA
Other	Positive-Pressure Dependency (Severe BPD) (binary)		Recorded at 36-weeks PMA
Other	Length at 36-weeks PMA	Length in centimeters	Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	General Movements Assessment (GMA) at 36-weeks corrected age	Prechtl's method for the qualitative assessment of general movements dysfunction	Recorded at 36-weeks PMA
Other	Time to enteral feed initiation		72 hours postnatal to 36-weeks PMA
Other	Time to a full enteral feed diet	Infant is weaned from intravenous fluids to a full enteral feed diet (delivery of feeds may be via an enteric tube)	72 hours postnatal to 36-weeks PMA
Other	Oral feeding status (binary)	Infant is taking all feeds by mouth (PO feeds) by 36-weeks PMA	Recorded at 36-weeks PMA
Other	Weight at 36-weeks PMA	Weight in grams	Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	Occipitofrontal circumference (OFC) at 36-weeks PMA	OFC in centimeters	Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	Body Mass Index (BMI) at 36-weeks PMA	BMI calculated by (BMI= weight in kg/length in meters squared)	Recorded at 36-weeks PMA or discharge if prior to 36-weeks
Other	Supplemental oxygen or positive-pressure respiratory support at 40-weeks PMA (binary)		Recorded at 40-weeks PMA
Other	Mortality by 22-26 months corrected age		Death occuring between 72-hours postnatal and 22-26 months corrected age
Other	Duration of ductal patency from 72-hours postnatal until 22 to 26-months corrected age follow-up		72 hours postnatal until 22-26 months follow-up visit
Other	Supplemental oxygen support (binary) at 22-26 months corrected age		Recorded at 22-26 months study follow-up visit
Other	Supplemental positive-pressure ventilation support (binary) at 22-26 months corrected age		Recorded at 22-26 months study follow-up visit
Other	Weight at 22-26 months corrected age	Weight in kilograms	Recorded at 22-26 months study follow-up visit
Other	Length at 22-26 months corrected age	Length in centimeters	Recorded at 22-26 months study follow-up visit
Other	Body Mass Index (BMI) at 22-26 months corrected age	BMI calculated by (BMI= weight in kg/length in meters squared)	Recorded at 22-26 months study follow-up visit
Other	Feeding status via full oral feeding or gastric-tube (binary) at 22-26 months corrected age		Recorded at 22-26 months study follow-up visit
Primary	Patent ductus arteriosus (PDA) closure documented via echocardiogram by 36-weeks postmenstrual age (PMA) (binary)	Documented closure of PDA on echocardiogram. Echocardiograms to document the primary outcome will be conducted weekly for the first four postnatal weeks and every other week thereafter, between study entry and 36-weeks PMA until PDA-closure is documented	Outcome will be documented between <72-hour screening echo and 36-weeks PMA.
Primary	Mortality or supplemental oxygen or positive-pressure respiratory support at 36-weeks PMA (binary)	Death occurring between study entry at <72-hours postnatal and 36-weeks PMA OR an oxygen or positive-pressure ventilation requirement at 36-weeks gestational age (=moderate bronchopulmonary dysplasia [BPD] or severe BPD)	Outcome will be documented between <72-hour screening echo and 36-weeks PMA
Primary	Composite Bayley III Motor Score at 22-26 months corrected age (continuous)	Composite motor score at 22 to 26-months postnatal as measured by Bayley Scales of Infant and Toddler Development- 3rd Edition (Bayley III)	Bayley III Score Testing will occur at 22 to 26 months corrected age (CA) (age since birth - number of weeks born before 40-weeks gestation)
Secondary	Mortality by 36-weeks PMA (binary)		Death occuring between 72-hours postnatal and 36-weeks PMA
Secondary	Bayley III Gross Motor Development Scaled Standard Score at 22-26 months corrected age (continuous)		Recorded at 22-26 months corrected age
Secondary	Bayley III Fine Motor Development Scaled Standard Score postnatal age at 22-26 months corrected age (continuous)		Recorded at 22-26 months corrected age
Secondary	Bayley III Cognitive Composite Score at 22-26 months corrected age (continuous)		Recorded at 22-26 months corrected age
Secondary	Bayley III Language Composite Score at 22-26 months corrected age (continuous)		Recorded at 22-26 months corrected age