Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants

Abstract

Importance The management of patent ductus arteriosus (PDA) in preterm infants is controversial. Objective 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). Design, Setting, and Participants 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. Interventions Infants with PDA were randomized to expectant management (n = 242) or active treatment (n = 240; acetaminophen, ibuprofen, or indomethacin) to close the PDA. Main Outcomes and Measures 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. Results 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. Conclusions and Relevance 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. Trial Registration ClinicalTrials.gov Identifier: NCT03456336

Affiliated Institutions

• Rainbow Babies & Children's Hospital US
• University at Buffalo, State University of New York US
• University of Utah US
• University of New Mexico US
• The University of Texas Health Science Center at Houston US
• Grady Memorial Hospital US
• Women's Hospital US
• University of Alabama at Birmingham US
• University of Rochester US
• Sanford Health US
• Case Western Reserve University US
• Emory University US
• Brown University US
• Lucile Packard Children's Hospital US
• University of Pennsylvania US
• Duke University US
• University of North Carolina at Chapel Hill US
• Children's Hospital of Philadelphia US
• Hospital of the University of Pennsylvania US
• Good Samaritan Hospital US
• Research Network (United States) US
• William P. Clements Jr. University Hospital US
• Northwestern University US
• University of Iowa US
• Sharp Mary Birch Hospital for Women & Newborns US
• University of Mississippi Medical Center US
• University of Cincinnati US
• Pennsylvania Hospital US
• RTI International US
• Stanford University US
• Nationwide Children's Hospital US
• Philadelphia University US
• Eunice Kennedy Shriver National Institute of Child Health and Human Development US
• East Carolina University US
• Jackson Memorial Hospital US
• The University of Texas Southwestern Medical Center US
• Virtua Voorhees Hospital US
• WakeMed US
• Parkland Memorial Hospital US
• Florida Gulf Coast University US

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