NCT03456336

Brief Summary

Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
482

participants targeted

Target at P50-P75 for phase_3

Timeline
12mo left

Started Feb 2019

Longer than P75 for phase_3

Geographic Reach
1 country

19 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress88%
Feb 2019May 2027

First Submitted

Initial submission to the registry

February 19, 2018

Completed
16 days until next milestone

First Posted

Study publicly available on registry

March 7, 2018

Completed
12 months until next milestone

Study Start

First participant enrolled

February 22, 2019

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 2, 2025

Completed
1.2 years until next milestone

Results Posted

Study results publicly available

May 12, 2026

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

May 30, 2027

Expected
Last Updated

May 12, 2026

Status Verified

April 1, 2026

Enrollment Period

6 years

First QC Date

February 19, 2018

Results QC Date

March 12, 2026

Last Update Submit

April 20, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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.

    Randomization to 36 weeks PMA

Secondary Outcomes (10)

  • Mortality at 36 Weeks PMA

    birth to 36 week postmenstrual age

  • Mortality Before Discharge

    birth to 120 days of life

  • Bronchopulmonary Dysplasia - Physiological Test

    birth to 36 week postmenstrual age

  • Bronchopulmonary Dysplasia - NIH Consensus Definition

    birth to 36 week postmenstrual age

  • Necrotizing Enterocolitis (NEC) at 36 Weeks PMA

    birth to 36 weeks post menstrual age

  • +5 more secondary outcomes

Other Outcomes (6)

  • Necrotizing Enterocolitis (NEC) at Status (2 Years)

    26 months corrected age

  • Retinopathy of Prematurity at Status (2 Years)

    26 months corrected age

  • Weight at Status (2 Years)

    26 months corrected age

  • +3 more other outcomes

Study Arms (2)

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.

Other: Active Treatment

Expectant Management Group

ACTIVE COMPARATOR

Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.

Other: Expectant Management

Interventions

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.

Active Treatment Group

Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.

Expectant Management Group

Eligibility Criteria

Age48 Hours - 21 Days
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Sharp Mary Birch Hospital for Women & Newborns

San Diego, California, 92123, United States

Location

Emory University

Atlanta, Georgia, 30303, United States

Location

Northwestern Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Mississippi Medical Center - Children's of Mississippi

Jackson, Mississippi, 39216, United States

Location

University of New Mexico

Albuquerque, New Mexico, 87131, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

RTI International

Durham, North Carolina, 27705, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cincinnati Children's Medical Center

Cincinnati, Ohio, 45267, United States

Location

Case Western Reserve University, Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106, United States

Location

Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Brown University - Women and Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Premature BirthDuctus Arteriosus, PatentInfant, Newborn, Diseases

Interventions

Watchful Waiting

Condition Hierarchy (Ancestors)

Obstetric Labor, PrematureObstetric Labor ComplicationsPregnancy ComplicationsFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesHeart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesHeart DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Outcome Assessment, Health CareOutcome and Process Assessment, Health CareQuality of Health CareHealth Services Administration

Results Point of Contact

Title
Matthew Laughon
Organization
University of North Carolina at Chapel Hill

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NETWORK
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 19, 2018

First Posted

March 7, 2018

Study Start

February 22, 2019

Primary Completion

March 2, 2025

Study Completion (Estimated)

May 30, 2027

Last Updated

May 12, 2026

Results First Posted

May 12, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will share

Per NIH Data Sharing Plan

Shared Documents
STUDY PROTOCOL, SAP

Locations