Management of the PDA Trial (PDA)

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.

Study Overview

• Status: Recruiting
• Conditions: Infant, Newborn, Diseases; Patent Ductus Arteriosus; Infant, Premature; Patent Ductus Arteriosus After Premature Birth
• Intervention / Treatment: Other: Active Treatment; Other: Expectant Management

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 Type: Interventional
• Enrollment (Estimated): 836
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Abhik Das, PhD; Phone Number: 301-230-4640
• Study Contact Backup: Name: Matthew Laughon, MD, MPH; Phone Number: 984-974-5063; Email: matt_laughon@med.unc.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama at Birmingham
      • Contact: Waldemar A. Carlo, MD
      • Principal Investigator: Waldemar A. Carlo, MD
  • California
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
      • Contact: Krisa P. Van Meurs, MD
      • Principal Investigator: Krisa P. Van Meurs, MD
    • San Diego, California, United States, 92123
      • Recruiting
      • Sharp Mary Birch Hospital for Women & Newborns
      • Contact: Anup Katheria, MD
      • Principal Investigator: Anup Katheria, MD
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Recruiting
      • Emory University
      • Contact: David P Carlton, MD
      • Principal Investigator: David P Carlton, MD
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Not yet recruiting
      • Northwestern Lurie Children's Hospital of Chicago
      • Contact: Aaron Hamvas, MD
      • Principal Investigator: Aaron Hamvas, MD
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Edward F. Bell, MD
      • Principal Investigator: Edward F. Bell, MD
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Not yet recruiting
      • University of Mississippi Medical Center - Children's of Mississippi
      • Principal Investigator: Abhay Bhatt, MD
      • Contact: Abhay Bhatt, MD
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • Recruiting
      • University of New Mexico
      • Contact: Kristi L. Watterberg, MD
      • Principal Investigator: Kristi L. Watterberg, MD
  • New York
    • Rochester, New York, United States, 14642
      • Active, not recruiting
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University
      • Contact: C. Michael Cotten, MD
      • Sub-Investigator: C. Michael Cotten, MD MHS
    • Durham, North Carolina, United States, 27705
      • Active, not recruiting
      • RTI International
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • Cincinnati Children's Medical Center
      • Contact: Brenda Poindexter, MD
      • Principal Investigator: Brenda Poindexter, MD
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Case Western Reserve University, Rainbow Babies and Children's Hospital
      • Contact: Michele C. Walsh, MD MS
      • Principal Investigator: Michele C. Walsh, MD MS
    • Columbus, Ohio, United States, 43205
      • Active, not recruiting
      • Research Institute at Nationwide Children's Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Eric Eichenwald, MD
      • Principal Investigator: Eric Eichenwald, MD
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Active, not recruiting
      • Brown University - Women and Infants Hospital of Rhode Island
  • Texas
    • Dallas, Texas, United States, 75235
      • Recruiting
      • University of Texas Southwestern Medical Center at Dallas
      • Contact: Myra Myckoff, MD
      • Principal Investigator: Myra Wyckoff, MD
    • Houston, Texas, United States, 77030
      • Recruiting
      • University of Texas Health Science Center at Houston
      • Principal Investigator: Jon E. Tyson, MD MPH
      • Contact: Jon E Tyson, MD MPH
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Recruiting
      • University of Utah
      • Contact: Bradley Yoder, MD
      • Principal Investigator: Bradley A. Yoder, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 days to 3 weeks (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Postnatal age 48 hours -21 days
• Infant 22 0/7 to 28 6/7 weeks gestation at birth

• sPDA, as defined as:

  1. Mild, Moderate, or Severe Clinical Criteria with Small or Moderate size PDA on echocardiogram
  2. Mild or Moderate Clinical Criteria with Large PDA on echocardiogram

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Treatment Group; 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; 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 Comparator: Expectant Management Group; Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.	Other: Expectant Management; Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death or Bronchopulmonary Dysplasia (BPD) at 36 weeks PMA	Death or BPD. BPD will be defined by the physiologic definition.	birth to 36 week postmenstrual age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality at 36 weeks PMA	mortality assessed at 36 week postmenstrual age	birth to 36 week postmenstrual age
Mortality before discharge	mortality assessed prior to hospital discharge	birth to 120 days of life
Bronchopulmonary dysplasia - Physiological Test	BPD defined by the physiologic test of oxygen therapy	birth to 36 week postmenstrual age
Bronchopulmonary dysplasia - NIH Consensus Definition	BPD defined by the NIH consensus definition of moderate or severe	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	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	birth to 36 weeks post menstrual age
Receipt of therapies designed to close the PDA	Defined as ligation or cardiac catheterization	birth to 120 days
Weight at 36 weeks PMA	Weight assessed at 36 weeks post menstrual age	birth to 36 weeks post menstrual age
Height at 36 weeks PMA	Height assessed at 36 weeks post menstrual age	birth to 36 weeks post menstrual age
Head Circumference at 36 weeks PMA	Head Circumference assessed at 36 weeks post menstrual age	birth to 36 weeks post menstrual age

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Necrotizing Enterocolitis (NEC) at status (2 years)	Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB	26 months corrected age
Retinopathy of Prematurity at status (2 years)	Stage 3 or worse in either eye AND as any intervention therapy-retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug	26 months corrected age
Weight at status (2 years)	Weight assessed at status (2 years)	26 months corrected age
Height at status (2 years)	Height assessed at status (2 years)	26 months corrected age
Head Circumference at status (2 years)	Head Circumference assessed at status (2 years)	26 months corrected age
Neurodevelopmental impairment (NDI) at status (2 years)	Severe NDI will be defined by any of the following: a BSID III cognitive score < 70, Gross Motor Functional (GMF) Level of 3-5, blindness (<20/200 vision) or profound hearing loss (inability to understand commands despite amplification); moderate NDI will be defined as a BSID III cognitive score 70-84 and either a GMF level of 2 or a hearing deficit requiring amplification to understand commands or unilateral blindness; mild NDI will be defined by a cognitive score 70-84, or a cognitive score ≥ 85 and any of the following: presence of a GMF level 1 or hearing loss not requiring amplification. Normal (no NDI) will be defined by a cognitive score ≥ 85 and absence of any neurosensory deficits.	26 months corrected age

Collaborators and Investigators

• Sponsor: NICHD Neonatal Research Network
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Publications and helpful links

Helpful Links

• NRN Website

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: February 19, 2018
• First Submitted That Met QC Criteria: February 28, 2018
• First Posted (Actual): March 7, 2018

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Heart Defects, Congenital; Cardiovascular Abnormalities; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Ductus Arteriosus, Patent; Infant, Newborn, Diseases
• Other Study ID Numbers: NICHD-NRN-0059; UG1HD112079 (U.S. NIH Grant/Contract); UG1HD112097 (U.S. NIH Grant/Contract); UG1HD112100 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Per NIH Data Sharing Plan
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No