Journal article
Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: The PDA Randomized Clinical Trial
JAMA : the journal of the American Medical Association, Vol.335(7), pp.588-599
02/17/2026
DOI: 10.1001/jama.2025.23330
PMCID: PMC12690482
PMID: 41364689
Abstract
The management of patent ductus arteriosus (PDA) in preterm infants is controversial.
To determine whether expectant management compared with active treatment of a protocol-defined PDA in preterm infants decreases the incidence of death or bronchopulmonary dysplasia (BPD).
A randomized clinical trial including infants born at 22 to 28 weeks' gestation and diagnosed with a protocol-defined PDA between the age of 48 hours and 21 days at screening. The trial was conducted from December 2018 to December 2024 at 33 hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. The final date of follow-up was June 2025.
Infants with PDA were randomized to expectant management (n = 242) or active treatment (n = 240; acetaminophen, ibuprofen, or indomethacin) to close the PDA.
The primary outcome was death or BPD at 36 weeks' postmenstrual age. The secondary outcomes included the components of the primary outcome and other morbidities of prematurity.
A total of 482 infants were randomized (median gestational age, 25 weeks [IQR, 24 to 27 weeks]; median birth weight, 760 g [IQR, 620 to 935 g]). The trial was stopped for futility and safety after the 50% interim analysis for the primary outcome due to higher survival in the expectant management group. The incidence of death or BPD was 80.9% (195/241) of infants in the expectant management group vs 79.6% (191/240) of infants in the active treatment group (adjusted risk difference, 1.2% [95% CI, -5.7% to 8.1%]; P = .73). The incidence of death before 36 weeks' postmenstrual age was 4.1% (10/241) of infants in the expectant management group vs 9.6% (23/240) of infants in the active treatment group (adjusted risk difference, -5.6% [95% CI, -10.1% to -1.2%]; P = .01). Infections resulting in death occurred in 0.8% (2/241) of infants in the expectant management group vs 3.8% (9/240) of infants in the active treatment group.
In extremely preterm infants with a protocol-defined PDA, death or BPD did not differ between the expectant management group and the active treatment group. Survival was substantially higher with expectant management.
ClinicalTrials.gov Identifier: NCT03456336.
Details
- Title: Subtitle
- Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: The PDA Randomized Clinical Trial
- Creators
- Matthew M Laughon - University of North Carolina at Chapel HillSonia M Thomas - RTI InternationalKristi L Watterberg - University of New MexicoKathleen A Kennedy - The University of Texas Health Science Center at HoustonMartin Keszler - Brown UniversityNamisavayam Ambalavanan - University of Alabama at BirminghamAlexis S Davis - Stanford UniversityJonathan L Slaughter - Nationwide Children's HospitalRonnie Guillet - University of RochesterTarah T Colaizy - University of IowaC Michael Cotten - Duke UniversityMegan A Dhawan - Children's Hospital of PhiladelphiaCarl L Bose - University of North Carolina at Chapel HillJennifer Talbert - RTI InternationalSarah Smucny - Case Western Reserve UniversityWilliam E Benitz - Lucile Packard Children's HospitalMatthew A Rysavy - The University of Texas Health Science Center at HoustonRobin K Ohls - University of UtahMariana C Baserga - University of UtahSara B DeMauro - Hospital of the University of PennsylvaniaMambarambath Jaleel - Parkland Memorial HospitalWesley M Jackson - University of North Carolina at Chapel HillWaldemar A Carlo - University of Alabama at BirminghamKaren M Puopolo - Pennsylvania HospitalAnna Maria Hibbs - Case Western Reserve UniversityAnup Katheria - Sharp Mary Birch Hospital for Women & NewbornsPablo J Sánchez - Nationwide Children's HospitalCarl T D'Angio - University of RochesterRavi M Patel - Emory UniversityBeth Ann Johnson - Good Samaritan HospitalValerie Y Chock - Lucile Packard Children's HospitalAbhay J Bhatt - University of Mississippi Medical CenterStephanie L Merhar - University of CincinnatiRyan Moore - East Carolina UniversityAbbot R Laptook - Brown UniversitySarvin Ghavam - Virtua Voorhees HospitalJanell Fuller - University of New MexicoShilpa Vyas-Read - Emory UniversityStephen D Kicklighter - WakeMedBaiba Steinbrekera - Sanford HealthKathryn Anderson - Sanford HealthAnne Marie Reynolds - University at Buffalo, State University of New YorkMyra H Wyckoff - William P. Clements Jr. University HospitalCassandra Montoya - Northwestern UniversityAbhik Das - RTI InternationalBarbara Do - RTI InternationalSamantha Chang - RTI InternationalRosemary D Higgins - Florida Gulf Coast UniversityMichele C Walsh - Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentEunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
- Resource Type
- Journal article
- Publication Details
- JAMA : the journal of the American Medical Association, Vol.335(7), pp.588-599
- DOI
- 10.1001/jama.2025.23330
- PMID
- 41364689
- PMCID
- PMC12690482
- NLM abbreviation
- JAMA
- ISSN
- 0098-7484
- eISSN
- 1538-3598
- Publisher
- AMER MEDICAL ASSOC
- Grant note
- National Institutes of Health (NIH)National Center for Advancing Translational Sciences (NCATS)Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
This study was supported by grants UG1 HD872293, UG1 HD112093, UG1 HD87226, UG1 HD68244, UG1 HD40689, UG1 HD40492, UG1 HD34216, UG1 HD68244, UG1 HD21364, UG1 HD112100, UG1 HD68278, UG1 HD68263, UG1 HD27851, UG1 HD27853, UG1 HD27880, UG1 HD112097, UG1 HD27853, UG1 HD40492, UG1 HD27904, UG1 HD68244, UG1 HD53089, UG1 HD27851, UG1 HD40492, UG1 HD53109, UG1 HD68263, UG1 HD40689, UG1 HD53109, UG1 HD112079, UG1 HD40492, and U24 HD95254 from the National Institutes of Health (NIH)Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)National Center for Advancing Translational Sciences (NCATS) and the and by grants UL1 TR1067, UL1 TR2489, UL1 TR454, UL1 TR1425, UL1 TR1085, UL1 TR1425, UL1 TR1449, UL1 TR454, UL1 TR442, and UL1 TR1117 from the . The grants were provided through cooperative agreements with the Neonatal Research Network (NRN) to support researchers who conduct rigorous multicenter clinical trials aiming to improve health care outcomes of neonates. The NRN centers and the data coordinating centers are chosen competitively every 5 to 7 years through open competition as per usual NIH peer review processes.
- Language
- English
- Electronic publication date
- 12/09/2025
- Date published
- 02/17/2026
- Academic Unit
- Stead Family Department of Pediatrics; Neonatology
- Record Identifier
- 9985090599502771
Metrics
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