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

NCT ID: NCT03782610

Last Updated: 2025-03-28

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 675 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-04-01
• Study Completion Date: 2026-06-30

Brief 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.

Conditions

Patent Ductus Arteriosus; Preterm Infant; Bronchopulmonary Dysplasia; Neurodevelopmental Abnormality

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Primary Study Cohort

450 Infants

No interventions assigned to this group

Validation Cohort

225 Infants. Will allow subsequent validation of models derived from the Primary Study Cohort.

No interventions assigned to this group

Eligibility Criteria

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)

• Maximum Eligible Age: 72 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Ohio State University

OTHER

Sponsor Role: collaborator

OhioHealth

OTHER

Sponsor Role: collaborator

Mount Carmel Health System

OTHER

Sponsor Role: collaborator

Nationwide Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Slaughter

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan L Slaughter, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital/The Ohio State University

Carl H Backes, MD

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital/The Ohio State University

Locations

Nationwide Children's Hospital Main Campus Neonatal Intensive Care Unit

Columbus, Ohio, United States

Nationwide Children's Neonatal Intensive Care Unit at The Ohio State University Wexner 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 Hospital Neonatal Intensive Care Unit at OhioHealth Grant Medical Center

Columbus, Ohio, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 26672023 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28046188 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29909074 (View on PubMed)

Runte KE, Flyer JN, Edwards EM, Soll RF, Horbar JD, Yeager SB. Variation of Patent Ductus Arteriosus Treatment in Very Low Birth Weight Infants. Pediatrics. 2021 Nov;148(5):e2021052874. doi: 10.1542/peds.2021-052874. Epub 2021 Oct 21.

Reference Type: DERIVED

PMID: 34675131 (View on PubMed)

Slaughter JL, Cua CL, Notestine JL, Rivera BK, Marzec L, Hade EM, Maitre NL, Klebanoff MA, Ilgenfritz M, Le VT, Lewandowski DJ, Backes CH. Early prediction of spontaneous Patent Ductus Arteriosus (PDA) closure and PDA-associated outcomes: a prospective cohort investigation. BMC Pediatr. 2019 Sep 13;19(1):333. doi: 10.1186/s12887-019-1708-z.

Reference Type: DERIVED

PMID: 31519154 (View on PubMed)

Provided Documents

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01HL145032

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1800684

Identifier Type: -

Identifier Source: org_study_id