Patent Ductus ArteriosusNCT03782610
Early Prediction of Spontaneous Patent Ductus Arteriosus (PDA) Closure and PDA-Associated Outcomes
An observational study of Patent Ductus Arteriosus and Preterm Infant, run by Nationwide Children's Hospital at 4 sites in United States.
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. Read more about this study
- Who is it for?
- Ages Up to 72 hours
- Conditions the study is for
- Patent Ductus Arteriosus, Preterm Infant, Bronchopulmonary Dysplasia
- How many people
- 526 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Apr 2019to Sep 2026
- How long will I take part?
- 22 Months
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 72 hours
- All sexes
- No healthy volunteers
- Child
Study population: A cohort of consecutively enrolled preterm infants born between 23- and 30-weeks gestation with patent ductus arteriosus (PDA) documented on echocardiogram within 72-hours postnatal.
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Nationwide Children's Hospital Main Campus Neonatal Intensive Care Unit
Columbus, Ohio, 43205
Nationwide Children's Neonatal Intensive Care Unit at The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210
Nationwide Children's Neonatal Intensive Care Unit at OhioHealth Riverside Methodist Hospital
Columbus, Ohio, 43214
Nationwide Children's Hospital Neonatal Intensive Care Unit at OhioHealth Grant Medical Center
Columbus, Ohio, 43215
About this study
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
- Keywords
- Patent Ductus Arteriosus, Preterm Infant, Echocardiogram, Prospective Cohort, Prediction Modeling
- Medical subject headings
- Ductus Arteriosus, Patent, Premature Birth, Bronchopulmonary Dysplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Primary Study Cohort | 450 Infants | |
| Validation Cohort | 225 Infants. Will allow subsequent validation of models derived from the Primary Study Cohort. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Outcome will be documented between <72-hour screening echo and 36-weeks PMA.
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)
Measured: Outcome will be documented between <72-hour screening echo and 36-weeks PMA
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)
Measured: 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 outcomes (5)
Mortality by 36-weeks PMA (binary)
Measured: Death occuring between 72-hours postnatal and 36-weeks PMA
Bayley III Gross Motor Development Scaled Standard Score at 22-26 months corrected age (continuous)
Measured: Recorded at 22-26 months corrected age
Bayley III Fine Motor Development Scaled Standard Score postnatal age at 22-26 months corrected age (continuous)
Measured: Recorded at 22-26 months corrected age
Bayley III Cognitive Composite Score at 22-26 months corrected age (continuous)
Measured: Recorded at 22-26 months corrected age
Bayley III Language Composite Score at 22-26 months corrected age (continuous)
Measured: Recorded at 22-26 months corrected age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2018
- Study start1 Apr 2019
- Primary completion31 Oct 2025
- Study completionSep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Patent Ductus ArteriosusStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 526 participants (actual)
- Target duration
- 22 Months
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Ohio State University, OhioHealth, Mount Carmel Health System
- Responsible party
- Principal investigator, Jonathan Slaughter, Nationwide Children's Hospital
- Investigators
- Jonathan L Slaughter, MD, MPH, Principal investigator, Nationwide Children's Hospital/The Ohio State UniversityCarl H Backes, MD, Principal investigator, Nationwide Children's Hospital/The Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03782610
- Sponsor's protocol ID
- 1800684
- Other IDs
- 1R01HL145032
- Status last verified
- Mar 2026
- First submitted
- 17 Dec 2018
- Last updated
- 10 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We welcome the opportunity to share data from our investigation. All patient identifiers will be removed from the final dataset. Following the completion and publication of our investigation, we will make the data available to other users under a data sharing agreement. We will ask under the agreement that other users will commit to using the data only for research purposes, that they will not identify individual study subjects, that they will securely store the data electronically using password protection or encryption, that they will delete or destroy the data after the completion of their investigation, and that they will acknowledge the contribution of the funding agency (NIH NHLBI) and our investigative team in collecting the original data.
Publications
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.
PubMed 26672023Slaughter 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.
PubMed 28046188Pavlek 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.
PubMed 29909074Runte 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.
PubMed 34675131Slaughter 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.
PubMed 31519154
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Prediction of Spontaneous Patent Ductus Arteriosus (PDA) Closure and PDA-Associated Outcomes
- ClinicalTrials.gov ID
- NCT03782610
- Acronym / sponsor ID
- 1800684
- Conditions
- Patent Ductus Arteriosus, Preterm Infant, Bronchopulmonary Dysplasia, Neurodevelopmental Abnormality
- Keywords
- Patent Ductus Arteriosus, Preterm Infant, Echocardiogram, Prospective Cohort, Prediction Modeling
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 526 participants (actual)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Ohio State University, OhioHealth, Mount Carmel Health System
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 31 Oct 2025 (actual)
- Study completion
- Sep 2026 (estimated)
- First posted
- 20 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 22 Months
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Primary Study Cohort | – | –450 Infants |
| Validation Cohort | – | –225 Infants. Will allow subsequent validation of models derived from the Primary Study Cohort. |
Who may qualify
- Ages
- Up to 72 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- A cohort of consecutively enrolled preterm infants born between 23- and 30-weeks gestation with patent ductus arteriosus (PDA) documented on echocardiogram within 72-hours postnatal.
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Patent ductus arteriosus (PDA) closure documented via echocardiogram by 36-weeks postmenstrual age (PMA) (binary)
Time frame: Outcome will be documented between <72-hour screening echo and 36-weeks PMA.
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
Mortality or supplemental oxygen or positive-pressure respiratory support at 36-weeks PMA (binary)
Time frame: Outcome will be documented between <72-hour screening echo and 36-weeks PMA
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)
Composite Bayley III Motor Score at 22-26 months corrected age (continuous)
Time frame: 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)
Composite motor score at 22 to 26-months postnatal as measured by Bayley Scales of Infant and Toddler Development- 3rd Edition (Bayley III)
5 secondary outcomes
Mortality by 36-weeks PMA (binary)
Time frame: Death occuring between 72-hours postnatal and 36-weeks PMA
Bayley III Gross Motor Development Scaled Standard Score at 22-26 months corrected age (continuous)
Time frame: Recorded at 22-26 months corrected age
Bayley III Fine Motor Development Scaled Standard Score postnatal age at 22-26 months corrected age (continuous)
Time frame: Recorded at 22-26 months corrected age
Bayley III Cognitive Composite Score at 22-26 months corrected age (continuous)
Time frame: Recorded at 22-26 months corrected age
Bayley III Language Composite Score at 22-26 months corrected age (continuous)
Time frame: Recorded at 22-26 months corrected age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2026.
- Background: PubMed 26672023Benitz 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.
- Background: PubMed 28046188Slaughter 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.
- Background: PubMed 29909074Pavlek 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.
- Derived from this study: PubMed 34675131Runte 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.
- Derived from this study: PubMed 31519154Slaughter 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.
- Individual participant dataSharing planned: Yes. We welcome the opportunity to share data from our investigation. All patient identifiers will be removed from the final dataset. Following the completion and publication of our investigation, we will make the data available to other users under a data sharing agreement. We will ask under the agreement that other users will commit to using the data only for research purposes, that they will not identify individual study subjects, that they will securely store the data electronically using password protection or encryption, that they will delete or destroy the data after the completion of their investigation, and that they will acknowledge the contribution of the funding agency (NIH NHLBI) and our investigative team in collecting the original data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jonathan L Slaughter, MD, MPH principal investigator
Nationwide Children's Hospital/The Ohio State University
Carl H Backes, MD principal investigator
Nationwide Children's Hospital/The Ohio State University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Patent Ductus Arteriosus and Preterm Infant, run by Nationwide Children's Hospital at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 10 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patent ductus arteriosus (PDA) closure documented via echocardiogram by 36-weeks postmenstrual age (PMA) (binary) (time frame: Outcome will be documented between <72-hour screening echo and 36-weeks PMA.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03782610, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Mar 2026.