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Management of the PDA Trial (PDA)

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ClinicalTrials.gov Identifier: NCT03456336
Recruitment Status : Not yet recruiting
First Posted : March 7, 2018
Last Update Posted : March 7, 2018
Sponsor:
Information provided by (Responsible Party):
NICHD Neonatal Research Network

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

Condition or disease Intervention/treatment Phase
Infant, Premature Patent Ductus Arteriosus Infant, Newborn, Diseases Patent Ductus Arteriosus After Premature Birth Other: Active Treatment Other: Expectant Management Phase 3

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  (Clinical Trial)
Estimated Enrollment : 1116 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Management of the Patent Ductus Arteriosus in Premature Infants Trial (PDA Trial)
Estimated Study Start Date : May 30, 2018
Estimated Primary Completion Date : May 30, 2022
Estimated Study Completion Date : July 31, 2024

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. Death or Bronchopulmonary Dysplasia (BPD) at 36 weeks PMA [ Time Frame: birth to 36 week postmenstrual age ]
    Death or BPD. BPD will be defined by the physiologic definition.


Secondary Outcome Measures :
  1. Mortality at 36 weeks PMA [ Time Frame: birth to 36 week postmenstrual age ]
    mortality assessed at 36 week postmenstrual age

  2. Mortality before discharge [ Time Frame: birth to 120 days of life ]
    mortality assessed prior to hospital discharge

  3. Bronchopulmonary dysplasia - Physiological Test [ Time Frame: birth to 36 week postmenstrual age ]
    BPD defined by the physiologic test of oxygen therapy

  4. Bronchopulmonary dysplasia - NIH Consensus Definition [ Time Frame: birth to 36 week postmenstrual age ]
    BPD defined by the NIH consensus definition of moderate or severe

  5. Necrotizing Enterocolitis (NEC) at 36 weeks PMA [ Time Frame: birth to 36 weeks post menstrual age ]
    Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB

  6. Retinopathy of Prematurity at 36 weeks PMA [ Time Frame: birth to 36 weeks post menstrual age ]
    Stage 3 or worse in either eye AND as any intervention therapy—retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug

  7. Receipt of therapies designed to close the PDA [ Time Frame: birth to 120 days ]
    Defined as ligation or cardiac catheterization

  8. Weight at 36 weeks PMA [ Time Frame: birth to 36 weeks post menstrual age ]
    Weight assessed at 36 weeks post menstrual age

  9. Height at 36 weeks PMA [ Time Frame: birth to 36 weeks post menstrual age ]
    Height assessed at 36 weeks post menstrual age

  10. Head Circumference at 36 weeks PMA [ Time Frame: birth to 36 weeks post menstrual age ]
    Head Circumference assessed at 36 weeks post menstrual age


Other Outcome Measures:
  1. Necrotizing Enterocolitis (NEC) at status (2 years) [ Time Frame: 26 months corrected age ]
    Proven NEC, no surgery, Stages IIA, IIB, or IIIA AND proven, surgery, Stage IIIB

  2. Retinopathy of Prematurity at status (2 years) [ Time Frame: 26 months corrected age ]
    Stage 3 or worse in either eye AND as any intervention therapy—retinal ablation, scleral buckle/vitrectomy, avastin or other anti-VEGF drug

  3. Weight at status (2 years) [ Time Frame: 26 months corrected age ]
    Weight assessed at status (2 years)

  4. Height at status (2 years) [ Time Frame: 26 months corrected age ]
    Height assessed at status (2 years)

  5. Head Circumference at status (2 years) [ Time Frame: 26 months corrected age ]
    Head Circumference assessed at status (2 years)

  6. Neurodevelopmental impairment (NDI) at status (2 years) [ Time Frame: 26 months corrected age ]
    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.



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Ages Eligible for Study:   up to 21 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03456336


Contacts
Contact: Matthew Laughon, MD, MPH 984-974-5063 matt_laughon@med.unc.edu
Contact: Rosemary Higgins, MD 301-435-7909 higginsr@mail.nih.gov

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35233
United States, California
Stanford University
Palo Alto, California, United States, 94304
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87131
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, North Carolina
RTI International
Durham, North Carolina, United States, 27705
Duke University
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati Children's Medical Center
Cincinnati, Ohio, United States, 45267
Case Western Reserve University, Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106
Research Institute at Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
United States, Rhode Island
Brown University - Women and Infants Hospital of Rhode Island
Providence, Rhode Island, United States, 02905
United States, Texas
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, United States, 75235
University of Texas Health Science Center at Houston
Houston, Texas, United States, 77030
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84108
Sponsors and Collaborators
NICHD Neonatal Research Network

Additional Information:
Responsible Party: NICHD Neonatal Research Network
ClinicalTrials.gov Identifier: NCT03456336     History of Changes
Other Study ID Numbers: NICHD-NRN-0059
First Posted: March 7, 2018    Key Record Dates
Last Update Posted: March 7, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Per NIH Data Sharing Plan
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
URL: http://

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Premature Birth
Ductus Arteriosus, Patent
Infant, Newborn, Diseases
Obstetric Labor, Premature
Obstetric Labor Complications
Pregnancy Complications
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Ibuprofen
Indomethacin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Gout Suppressants
Tocolytic Agents
Reproductive Control Agents