Infant, PrematurePhase 3PDANCT03456336
Management of the PDA Trial
A Phase 3 study testing Active Treatment and Expectant Management in people with Infant, Premature and Patent Ductus Arteriosus, run by NICHD Neonatal Research Network at 19 sites in United States.
Trial summary
Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants. Read more about this study
- Who is it for?
- Ages 48 hours to 21 days
- Conditions the study is for
- Infant, Premature, Patent Ductus Arteriosus, Infant, Newborn, Diseases
- What is being tested?
- Active Treatment and Expectant Management
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 482 participants
- Where
- 19 sitesUnited States
- Study dates
- 22 Feb 2019to 30 May 2027
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 48 hours to 21 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Postnatal age 48 hours -21 days
- Infant 22 0/7 to 28 6/7 weeks gestation at birth
- sPDA, as defined as:
- Mild, Moderate, or Severe Clinical Criteria with Small or Moderate size PDA on echocardiogram
- Mild or Moderate Clinical Criteria with Large PDA on echocardiogram
Who cannot join
- Cardiopulmonary compromise
- Known congenital heart disease (besides atrial septal defect or ventricular septal defect)
- Known pulmonary malformation (e.g. congenital lobar emphysema, congenital pulmonary adenomatous malformation)
- Any condition which, in the opinion of the investigator, would preclude enrollment
Trial locations and contacts
19 sites in 1 country.
19 sites in 1 country
United States19 sites
University of New Mexico
Albuquerque, New Mexico, 87131
Emory University
Atlanta, Georgia, 30303
University of Alabama at Birmingham
Birmingham, Alabama, 35233
Northwestern Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Medical Center
Cincinnati, Ohio, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
Research Institute at Nationwide Children's Hospital
Columbus, Ohio, 43205
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75235
RTI International
Durham, North Carolina, 27705
Duke University
Durham, North Carolina, 27710
University of Texas Health Science Center at Houston
Houston, Texas, 77030
University of Iowa
Iowa City, Iowa, 52242
University of Mississippi Medical Center - Children's of Mississippi
Jackson, Mississippi, 39216
Stanford University
Palo Alto, California, 94304
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Brown University - Women and Infants Hospital of Rhode Island
Providence, Rhode Island, 02905
University of Rochester
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84108
Sharp Mary Birch Hospital for Women & Newborns
San Diego, California, 92123
About this study
Official title: Management of the Patent Ductus Arteriosus in Premature Infants Trial (PDA Trial)
Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.
Read the detailed description
This is a pragmatic randomized multicenter, effectiveness study comparing active treatment of a symptomatic patent ductus arteriosus (sPDA) to expectant management. We hypothesize in premature infants with a sPDA, expectant management reduces the incidence proportion of death or BPD by 10% (from 50% to 40%) when compared to active treatment.
Participants with a sPDA allocated to the active treatment arm will receive intravenous administration of indomethacin or ibuprofen (depending on center preference). The decision to ligate will be left to the clinical team. Participants with a sPDA allocated to the expectant management arm will receive supportive care at the clinical team's discretion and will receive indomethacin/ibuprofen or ligation if the infant develops cardiopulmonary compromise. The decision to ligate will be left to the clinical team.
The primary endpoint for the study will be death or BPD (as assessed by the physiologic definition) at 36 weeks postmenstrual age (PMA).
- Conditions
- Infant, Premature, Patent Ductus Arteriosus, Infant, Newborn, Diseases, Patent Ductus Arteriosus After Premature Birth
- Being tested
- Active Treatment, Expectant Management
- Medical subject headings
- Premature Birth, Ductus Arteriosus, Patent, Infant, Newborn, Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active TreatmentOther
Infants assigned to the active treatment group will receive indomethacin or ibuprofen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other. If the infant receives both, it will be considered a protocol violation.
Expectant ManagementOther
Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.
| Study group | Role | What they receive |
|---|---|---|
| Active Treatment Group | Active comparator | Infants assigned to the active treatment group will receive indomethacin or ibuprofen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other. Receives: Other: Active Treatment |
| Expectant Management Group | Active comparator | Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs. Receives: Other: Expectant Management |
What is being measured
The primary outcome is the main question the study is designed to answer.
Death or Bronchopulmonary Dysplasia (BPD) at 36 Weeks PMA
A composite outcome for infants who were diagnosed with physiologic bronchopulmonary dysplasia (BPD) or died by 36 weeks postmenstrual age (PMA). Physiologic BPD is determined using existing Neonatal Research Network Generic Database criteria at 36 weeks PMA. Infants alive an in hospital are classified based on respiratory status at 36 weeks PMA or by a room air weaning challenge performed between 36 and 37 weeks PMA. Infants who are transferred or discharged before 36 weeks are classified based on the support they are receiving at that time. Infants who died before 36 weeks PMA are not assessed for BPD. Deaths include all-cause deaths between randomization and 36 weeks PMA.
Measured: Randomization to 36 weeks PMA
Secondary outcomes (10)
Mortality at 36 Weeks PMA
mortality assessed at 36 week postmenstrual age
Measured: birth to 36 week postmenstrual age
Mortality Before Discharge
mortality assessed prior to hospital discharge
Measured: birth to 120 days of life
Bronchopulmonary Dysplasia - Physiological Test
BPD defined by the physiologic test of oxygen therapy
Measured: birth to 36 week postmenstrual age
Bronchopulmonary Dysplasia - NIH Consensus Definition
BPD defined by the NIH consensus definition of moderate or severe
Measured: birth to 36 week postmenstrual age
Necrotizing Enterocolitis (NEC) at 36 Weeks PMA
Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB
Measured: birth to 36 weeks post menstrual age
Retinopathy of Prematurity at 36 Weeks PMA
Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug
Measured: birth to 36 weeks post menstrual age
Receipt of Therapies Designed to Close the PDA
Defined as ligation or cardiac catheterization
Measured: birth to 120 days
Weight at 36 Weeks PMA
Weight assessed at 36 weeks post menstrual age
Measured: birth to 36 weeks post menstrual age
Height at 36 Weeks PMA
Height assessed at 36 weeks post menstrual age
Measured: birth to 36 weeks post menstrual age
Head Circumference at 36 Weeks PMA
Head Circumference assessed at 36 weeks post menstrual age
Measured: birth to 36 weeks post menstrual age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2018
- Study start22 Feb 2019
- Primary completion2 Mar 2025
- Study completion30 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infant, PrematureStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 482 participants (actual)
Sponsor and investigators
- Lead sponsor
- NICHD Neonatal Research Network
- Sponsor type
- Research network
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03456336
- Sponsor's protocol ID
- NICHD-NRN-0059
- Other IDs
- UG1HD112079, UG1HD112097, UG1HD112100
- Acronym
- PDA
- Status last verified
- Apr 2026
- First submitted
- 19 Feb 2018
- Last updated
- 12 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Per NIH Data Sharing Plan
Publications
Laughon MM, Thomas SM, Watterberg KL, Kennedy KA, Keszler M, Ambalavanan N, Davis AS, Slaughter JL, Guillet R, Colaizy TT, Cotten CM, Dhawan MA, Bose CL, Talbert J, Smucny S, Benitz WE, Rysavy MA, Ohls RK, Baserga MC, DeMauro SB, Jaleel M, Jackson WM, Carlo WA, Puopolo KM, Hibbs AM, Katheria A, Sanchez PJ, D'Angio CT, Patel RM, Johnson BA, Chock VY, Bhatt AJ, Merhar SL, Moore R, Laptook AR, Ghavam S, Fuller J, Vyas-Read S, Kicklighter SD, Steinbrekera B, Anderson K, Chandrasekharan PK, Wyckoff MH, Montoya C, Das A, Do B, Chang S, Higgins RD, Walsh MC; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: The PDA Randomized Clinical Trial. JAMA. 2026 Feb 17;335(7):588-599. doi: 10.1001/jama.2025.23330.
PubMed 41364689
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Management of the Patent Ductus Arteriosus in Premature Infants Trial (PDA Trial)
- ClinicalTrials.gov ID
- NCT03456336
- Acronym / sponsor ID
- PDA / NICHD-NRN-0059
- Conditions
- Infant, Premature, Patent Ductus Arteriosus, Infant, Newborn, Diseases, Patent Ductus Arteriosus After Premature Birth
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 482 participants (actual)
- Lead sponsor
- NICHD Neonatal Research NetworkResearch network
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 22 Feb 2019 (actual)
- Primary completion
- 2 Mar 2025 (actual)
- Study completion
- 30 May 2027 (estimated)
- First posted
- 7 Mar 2018 (actual)
- Results
- Posted 12 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.
Detailed description
This is a pragmatic randomized multicenter, effectiveness study comparing active treatment of a symptomatic patent ductus arteriosus (sPDA) to expectant management. We hypothesize in premature infants with a sPDA, expectant management reduces the incidence proportion of death or BPD by 10% (from 50% to 40%) when compared to active treatment.
Participants with a sPDA allocated to the active treatment arm will receive intravenous administration of indomethacin or ibuprofen (depending on center preference). The decision to ligate will be left to the clinical team. Participants with a sPDA allocated to the expectant management arm will receive supportive care at the clinical team's discretion and will receive indomethacin/ibuprofen or ligation if the infant develops cardiopulmonary compromise. The decision to ligate will be left to the clinical team.
The primary endpoint for the study will be death or BPD (as assessed by the physiologic definition) at 36 weeks postmenstrual age (PMA).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Treatment Group | Active comparator | Other: Active TreatmentInfants assigned to the active treatment group will receive indomethacin or ibuprofen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other. |
| Expectant Management Group | Active comparator | Other: Expectant ManagementInfants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs. |
Who may qualify
- Ages
- 48 hours to 21 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Postnatal age 48 hours -21 days
- Infant 22 0/7 to 28 6/7 weeks gestation at birth
- sPDA, as defined as:
Key exclusion criteria (4 listed)
- Cardiopulmonary compromise
- Known congenital heart disease (besides atrial septal defect or ventricular septal defect)
- Known pulmonary malformation (e.g. congenital lobar emphysema, congenital pulmonary adenomatous malformation)
- Any condition which, in the opinion of the investigator, would preclude enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active TreatmentInfants assigned to the active treatment group will receive indomethacin or ibuprofen per their local site usual care dosing and schedule if the infant has a sPDA. The choice of indomethacin or ibuprofen will be left to the center, however, infants may only receive one or the other. If the infant receives both, it will be considered a protocol violation. | Other | Active Treatment Group |
| Expectant ManagementInfants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs. | Other | Expectant Management Group |
Primary outcome
Death or Bronchopulmonary Dysplasia (BPD) at 36 Weeks PMA
Time frame: Randomization to 36 weeks PMA
A composite outcome for infants who were diagnosed with physiologic bronchopulmonary dysplasia (BPD) or died by 36 weeks postmenstrual age (PMA). Physiologic BPD is determined using existing Neonatal Research Network Generic Database criteria at 36 weeks PMA. Infants alive an in hospital are classified based on respiratory status at 36 weeks PMA or by a room air weaning challenge performed between 36 and 37 weeks PMA. Infants who are transferred or discharged before 36 weeks are classified based on the support they are receiving at that time. Infants who died before 36 weeks PMA are not assessed for BPD. Deaths include all-cause deaths between randomization and 36 weeks PMA.
10 secondary outcomes
Mortality at 36 Weeks PMA
Time frame: birth to 36 week postmenstrual age
Mortality Before Discharge
Time frame: birth to 120 days of life
Bronchopulmonary Dysplasia - Physiological Test
Time frame: birth to 36 week postmenstrual age
Bronchopulmonary Dysplasia - NIH Consensus Definition
Time frame: birth to 36 week postmenstrual age
Necrotizing Enterocolitis (NEC) at 36 Weeks PMA
Time frame: birth to 36 weeks post menstrual age
Retinopathy of Prematurity at 36 Weeks PMA
Time frame: birth to 36 weeks post menstrual age
Receipt of Therapies Designed to Close the PDA
Time frame: birth to 120 days
Weight at 36 Weeks PMA
Time frame: birth to 36 weeks post menstrual age
Height at 36 Weeks PMA
Time frame: birth to 36 weeks post menstrual age
Head Circumference at 36 Weeks PMA
Time frame: birth to 36 weeks post menstrual age
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41364689Laughon MM, Thomas SM, Watterberg KL, Kennedy KA, Keszler M, Ambalavanan N, Davis AS, Slaughter JL, Guillet R, Colaizy TT, Cotten CM, Dhawan MA, Bose CL, Talbert J, Smucny S, Benitz WE, Rysavy MA, Ohls RK, Baserga MC, DeMauro SB, Jaleel M, Jackson WM, Carlo WA, Puopolo KM, Hibbs AM, Katheria A, Sanchez PJ, D'Angio CT, Patel RM, Johnson BA, Chock VY, Bhatt AJ, Merhar SL, Moore R, Laptook AR, Ghavam S, Fuller J, Vyas-Read S, Kicklighter SD, Steinbrekera B, Anderson K, Chandrasekharan PK, Wyckoff MH, Montoya C, Das A, Do B, Chang S, Higgins RD, Walsh MC; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: The PDA Randomized Clinical Trial. JAMA. 2026 Feb 17;335(7):588-599. doi: 10.1001/jama.2025.23330.
- NRN WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Per NIH Data Sharing Plan
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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.
The record lists no contact. Use the official record to reach the sponsor.
19 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Active Treatment and Expectant Management in people with Infant, Premature and Patent Ductus Arteriosus, run by NICHD Neonatal Research Network at 19 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 5 inclusion and 4 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 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Death or Bronchopulmonary Dysplasia (BPD) at 36 Weeks PMA (time frame: Randomization to 36 weeks PMA). 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 NCT03456336, which also lists 1 linked publication.
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 12 May 2026.