Management of the PDA Trial (PDA)

• ClinicalTrials.gov Identifier: NCT03456336
• Recruitment Status: Recruiting
• First Posted: March 7, 2018
• Last Update Posted: March 22, 2023
• Sponsor: NICHD Neonatal Research Network
• Information provided by (Responsible Party): NICHD Neonatal Research Network

Tracking Information

• First Submitted Date: February 19, 2018
• First Posted Date: March 7, 2018
• Last Update Posted Date: March 22, 2023
• Actual Study Start Date: December 3, 2018
• Estimated Primary Completion Date: March 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2018)

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 28, 2018)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: February 28, 2018)

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

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Management of the PDA Trial
• Official Title: Management of the Patent Ductus Arteriosus in Premature Infants Trial (PDA Trial)
• Brief Summary: Estimate the risks and benefits of active treatment versus expectant management of a symptomatic patent ductus arteriosus (sPDA) in premature infants.

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
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Infant, Premature
• Patent Ductus Arteriosus
• Infant, Newborn, Diseases
• Patent Ductus Arteriosus After Premature Birth

Intervention

• 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.
• Other: Expectant Management
  Infants assigned to the expectant management group will receive indomethacin or ibuprofen if cardiopulmonary compromise occurs.

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 28, 2018): 1116
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2029
• Estimated Primary Completion Date: March 2027 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 48 Hours to 21 Days (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Matthew Laughon, MD, MPH; 984-974-5063; matt_laughon@med.unc.edu

Contact: Abhik Das, PhD; 301-230-4640

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03456336
• Other Study ID Numbers: NICHD-NRN-0059
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Per NIH Data Sharing Plan
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)

• Current Responsible Party: NICHD Neonatal Research Network
• Original Responsible Party: Same as current
• Current Study Sponsor: NICHD Neonatal Research Network
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: NICHD Neonatal Research Network
• Verification Date: March 2023