Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: The PDA Randomized Clinical Trial.
| Title: | Expectant Management vs Medication for Patent Ductus Arteriosus in Preterm Infants: The PDA Randomized Clinical Trial. |
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| Authors: | Laughon MM; Department of Pediatrics, University of North Carolina at Chapel Hill.; Thomas SM; Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, North Carolina.; Watterberg KL; Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque.; Kennedy KA; McGovern Medical School, University of Texas Health Science Center, Houston.; Keszler M; Department of Pediatrics, Warren Alpert Medical School, Brown University, Providence, Rhode Island.; Ambalavanan N; Division of Neonatology, University of Alabama, Birmingham.; Davis AS; Lucile Packard Children's Hospital Stanford, Stanford University, Palo Alto, California.; Slaughter JL; Nationwide Children's Hospital, College of Medicine, Ohio State University, Columbus.; Guillet R; Division of Neonatology, School of Medicine and Dentistry, University of Rochester, Rochester, New York.; Colaizy TT; Department of Pediatrics, University of Iowa, Iowa City.; Cotten CM; Department of Pediatrics, Duke University, Durham, North Carolina.; Dhawan MA; Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia.; Bose CL; Department of Pediatrics, University of North Carolina at Chapel Hill.; Talbert J; Department of Pediatrics, University of North Carolina at Chapel Hill.; Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, North Carolina.; Smucny S; Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio.; Benitz WE; Lucile Packard Children's Hospital Stanford, Stanford University, Palo Alto, California.; Rysavy MA; McGovern Medical School, University of Texas Health Science Center, Houston.; Ohls RK; University of Utah Health Sciences Center, Salt Lake City.; Baserga MC; University of Utah Health Sciences Center, Salt Lake City.; DeMauro SB; Hospital of the University of Pennsylvania, Philadelphia.; Jaleel M; Parkland Memorial Hospital, University of Texas Southwestern Medical Center, Dallas.; Jackson WM; Department of Pediatrics, University of North Carolina at Chapel Hill.; Carlo WA; Division of Neonatology, University of Alabama, Birmingham.; Puopolo KM; Pennsylvania Hospital, Philadelphia.; Hibbs AM; Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio.; Katheria A; Sharp Mary Birch Hospital for Women and Newborns, San Diego, California.; Sánchez PJ; Nationwide Children's Hospital, College of Medicine, Ohio State University, Columbus.; D'Angio CT; Division of Neonatology, School of Medicine and Dentistry, University of Rochester, Rochester, New York.; Patel RM; Department of Pediatrics, Emory University, Atlanta, Georgia.; Johnson BA; Good Samaritan Hospital, Cincinnati, Ohio.; Chock VY; Lucile Packard Children's Hospital Stanford, Stanford University, Palo Alto, California.; Bhatt AJ; Department of Pediatrics, University of Mississippi Medical Center, Jackson.; Merhar SL; University of Cincinnati Hospital, Cincinnati, Ohio.; Moore R; Maynard Children's Hospital, East Carolina University Health, Greenville, North Carolina.; Laptook AR; Department of Pediatrics, Warren Alpert Medical School, Brown University, Providence, Rhode Island.; Ghavam S; Virtua Voorhees Hospital, Voorhees, New Jersey.; Fuller J; Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque.; Vyas-Read S; Grady Memorial Hospital, Emory University, Atlanta, Georgia.; Kicklighter SD; WakeMed Health and Hospitals, Raleigh, North Carolina.; Steinbrekera B; Sanford Health, Sioux Falls, South Dakota.; Anderson K; Sanford Health, Sioux Falls, South Dakota.; Chandrasekharan PK; Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York.; Wyckoff MH; William P. Clements Jr University Hospital, Dallas, Texas.; Montoya C; Prentice Women's Hospital, Northwestern University, Chicago, Illinois.; Das A; Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, Maryland.; Do B; Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, North Carolina.; Chang S; Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, North Carolina.; Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.; Research and Sponsored Programs, Florida Gulf Coast University, Fort Myers.; Walsh MC; Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland. |
| Corporate Authors: | Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network |
| Source: | JAMA [JAMA] 2026 Feb 17; Vol. 335 (7), pp. 588-599. |
| Publication Type: | Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Pragmatic Clinical Trial; Randomized Controlled Trial |
| Language: | English |
| Journal Info: | Publisher: American Medical Association Country of Publication: United States NLM ID: 7501160 Publication Model: Print Cited Medium: Internet ISSN: 1538-3598 (Electronic) Linking ISSN: 00987484 NLM ISO Abbreviation: JAMA Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Chicago : American Medical Association, 1960- |
| MeSH Terms: | Bronchopulmonary Dysplasia*/epidemiology ; Bronchopulmonary Dysplasia*/etiology ; Bronchopulmonary Dysplasia*/prevention & control ; Ductus Arteriosus, Patent*/complications ; Ductus Arteriosus, Patent*/mortality ; Ductus Arteriosus, Patent*/therapy ; Infant, Premature, Diseases*/mortality ; Infant, Premature, Diseases*/therapy ; Watchful Waiting*; Acetaminophen/therapeutic use ; Acetaminophen/adverse effects ; Ibuprofen/therapeutic use ; Ibuprofen/adverse effects ; Indomethacin/therapeutic use ; Indomethacin/adverse effects ; Female ; Humans ; Infant, Newborn ; Male ; Gestational Age ; Incidence ; Infant Death ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Kaplan-Meier Estimate ; Treatment Outcome |
| 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. |
| Comments: | Comment in: JAMA. 2026 Feb 17;335(7):580-582. doi: 10.1001/jama.2025.23935.. (PMID: 41364680); Erratum in: JAMA. 2026 Mar 19. doi: 10.1001/jama.2026.2697.. (PMID: 41854607) |
| Grant Information: | UG1 HD068263 United States HD NICHD NIH HHS; UG1 HD087226 United States HD NICHD NIH HHS; U01 HD036790 United States HD NICHD NIH HHS; UM1 TR004406 United States TR NCATS NIH HHS; UG1 HD040689 United States HD NICHD NIH HHS; UG1 HD112100 United States HD NICHD NIH HHS; UG1 HD112097 United States HD NICHD NIH HHS; UG1 HD034216 United States HD NICHD NIH HHS; UG1 HD027904 United States HD NICHD NIH HHS; UL1 TR001085 United States TR NCATS NIH HHS; UG1 HD027880 United States HD NICHD NIH HHS; UL1 TR001117 United States TR NCATS NIH HHS; UG1 HD053109 United States HD NICHD NIH HHS; UG1 HD027851 United States HD NICHD NIH HHS; U10 HD034216 United States HD NICHD NIH HHS; UL1 TR001067 United States TR NCATS NIH HHS; UG1 HD068244 United States HD NICHD NIH HHS; UG1 HD027853 United States HD NICHD NIH HHS; UG1 HD112093 United States HD NICHD NIH HHS; UL1 TR001449 United States TR NCATS NIH HHS; UG1 HD053089 United States HD NICHD NIH HHS; UL1 TR002489 United States TR NCATS NIH HHS; U10 HD040689 United States HD NICHD NIH HHS; U10 HD040492 United States HD NICHD NIH HHS; UL1 TR001425 United States TR NCATS NIH HHS; UG1 HD040492 United States HD NICHD NIH HHS; UG1 HD021364 United States HD NICHD NIH HHS; UG1 HD112079 United States HD NICHD NIH HHS; UG1 HD068278 United States HD NICHD NIH HHS; U24 HD095254 United States HD NICHD NIH HHS |
| Contributed Indexing: | Investigator: SJ Weiner; AM Hensman; K Porras; L St Pierre; E Vieira; R Henry; AH Aaron Hamvas; RA deRegnier; C Montoya; DT Robinson; SM Ward; BS Siner; S Smucny; NS Newman; DE Wilson-Costello; T Beiersdorfer; A Graber-Pels; C Grisby; M Hess; J Kim; C King; K Kirker; H Kramer; K McKeown; G Muthig; L Radcliff; C Reid; D Russell; K Schibler; J Thompson; ME D'Alton; RA Polin; KA Fisher; RN Goldberg; S Aleem; M Babilonia-Rosa; K Bear; V Bergstedt; C Clark; J Finkle; S Makhijani; S Moseley; C Stone; J Talbert; DP Carlton; D Bottcher; S Connor; J Laursen; Y Loggins; C Mackie; J Thompson; M Willinger; AA Bremer; RD Higgins; SW Archer; MC Allen; G Dominguez; AM Khan; R Pucio; E Stephens; J Wade; N Batterson; H Baugher; DR Beckford; K Benninger; C Boyle; C Cobe; R Cotterman; B DeSantis; HS Dixit; M Glaze; C Hanlon; J Knox; R Kumar; P Luzader; EF Mark; L Marzec; J McCool; K McGovern; G Mendez; B Miller; T Naik; MA Nelin; T Pennington; J Randle; M Resetar; J Schiering; K Schmidt; S Shepherd; K Small; M Stein; RA Sullivan; A Talliker; AM Tice; K Warnimont; E Zettler; JW Pickett; KM Zaterka-Baxter; JO Auman; A Lewis; A Mazur; G Aliyev; K Arnell; R Dorner; F Ines; J Koo; A Peirson; C Peterson; J Sauberan; MB Ball; JE Chuck; AS Davis; KK Morris; BP Recine; KP Van Meurs; G Green; L Rutkowska; T Clemons; RL Benz; CL Buie; KM Foshee; S Gentle; SE Owen; AA Salas; VS Shukla; CP Travers; SM Turner; SS Cosby; TE McNair; R Steinhorn; M Broadbent; C Elenkiwich; EF Bell; CA Goeke; MM Henning; LA Hogden; KJ Johnson; PJ McNamara; ML Schmelzel; JR Walker; S Van Muyden; CA Giachelli; NJ Taylor; M Famuyide; S Hodges; S Jackson; C McKenzie; NJ Salazar; SS Beauman; E Kuan; J Montoya; MA Dhawan; EC Eichenwald; L Booth; C Catts; M Crisafulli; MC Gambacorta; T Mancini; J Snyder; K Zola; HIM Wadkins; K Binion; M Bowman; E Boylin; J Donato; R Jensen; R Jones; A Kent; E Li; K Mckee; M Moreland; P Sabaratnam; AM Scorsone; K Voelker; L Brion; A Chavez; J Duran; VS Kapadia; M Kawamura; M Lemler; L Roblyer; P Sepulveda; MH Webbon; K Coleman; B Davis; TM Bahr; M Baserga; LM Bell; JO Elmont; EB Gerday; SE Johnson; MC Loertscher; DK Magana; T Marchant; KM McGrath; HG Mickelsen; SD Minton; DM Parry; BJ Petersen; MJ Sheffield; KD Woodbury; D Bentley; LC Bledsoe; S Christensen; R Fisher; L Floyd; SS Moody; R Pierce; BA Reich; B Scullin; K Weaver-Lewis; BA Yoder; RJ Boyle; CA Gleason |
| Molecular Sequence: | ClinicalTrials.gov NCT03456336 |
| Substance Nomenclature: | 362O9ITL9D (Acetaminophen); WK2XYI10QM (Ibuprofen); XXE1CET956 (Indomethacin) |
| Entry Date(s): | Date Created: 20251209 Date Completed: 20260217 Latest Revision: 20260319 |
| Update Code: | 20260319 |
| PubMed Central ID: | PMC12690482 |
| DOI: | 10.1001/jama.2025.23330 |
| PMID: | 41364689 |
| Database: | MEDLINE |
Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Pragmatic Clinical Trial; Randomized Controlled Trial