Early Treatment Versus Delayed Conservative Treatment of the Patent Ductus Arteriosus
Condition: Patent Ductus Arteriosus; Surgery; Necrotizing Enterocolitis; Intestinal Perforation
MeSH terms: Enterocolitis; Enterocolitis, Necrotizing; Intestinal Perforation; Ductus Arteriosus, Patent
Intervention: pharmacologic treatment of the PDA; no pharmacologic treatment of the PDA; NSAID
Intervention description: Following randomization, infants will be treated with medications used to produce PDA closure.; Following randomization, infants will NOT be treated with medications used to produce PDA closure (unless they develop rescue criteria at a later point in time).; Indomethacin, ibuprofen or acetaminophen will be used as standard of care treatment
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Early routine, mandated PDA treatment versus Conservative treatment only if Rescue criteria are met
Masking: Single (Outcomes Assessor)
Enrollment: 202.0
Sex: All
Minimum age: 5 Days
Maximum age: 14 Days
Healthy volunteers: No
Keywords: patent ductus arteriosus; patent ductus arteriosus ligation; necrotizing enterocolitis; spontaneous intestinal perforation

Summary:

      The primary goal of the trial is to compare two different Patent Ductus Arteriosus (PDA)
      treatment approaches: 1) an "early treatment" approach or 2) a "conservative" approach. For
      the purposes of the study infants will be enrolled if they are delivered before 28 weeks
      gestation and have a moderate/large PDA present at 5-7 days after birth.

      The hypothesis is: treatment of a moderate size patent ductus arteriosus (PDA) will decrease
      the time needed for assisted respiratory support, diuretic therapy, and gavage feeding
      assistance, in addition to decreasing the incidence of ductus ligations or need for future
      outpatient cardiology follow-up appointments. The investigators hypothesize that one or more
      of these benefits will occur without an increase in the time taken to achieve full enteral
      feedings or in the incidence of necrotizing enterocolitis (NEC) or spontaneous intestinal
      perforations (SIP).The investigators will be comparing the effectiveness of early
      pharmacologic treatment with a control group of conservatively managed infants who will only
      receive treatment if they meet specific criteria for "rescue treatment".
    

Eligibility criteria:

        Inclusion Criteria:

        This will be a prospective randomized, multi-center, controlled trial that will enroll
        infants delivered between 23 & 0/7 - 27 & 6/7 weeks gestation:

          1. infants must be between 5-14 days old (if delivered between 23 and 0/7 - 25 and 6/7
             weeks) or 7-14 days old (if delivered between 26 & 0/7 - 27 & 6/7 weeks) and

          2. have a "moderate size PDA" (defined as a PDA on echocardiogram that has at least one
             of the following criteria: internal ductus diameter ≥1.5 mm/kg (or PDA:LPA ratio
             ≥0.5), ductus flow velocity ≤2.5 m/s or mean pressure gradient across the ductus <8
             mm, LA/Ao ratio ≥1.5, left pulmonary artery diastolic (or mean) flow velocity >0.2 (or
             >0.42) m/sec, respectively, and/or reversed diastolic flow in the descending
             aorta)(13, 68, 69) and

          3. are receiving respiratory support consisting of either mechanical ventilation, nasal
             CPAP, SiPAP, or nasal cannula flow ≥2 L/min.

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             Exclusion Criteria:

             prior treatment with indomethacin, ibuprofen, or acetaminophen, contraindications for
             the use of indomethacin, ibuprofen, or acetaminophen (these include: hydrocortisone
             administration within 24 hrs, urine output < 1 ml/kg/h during the preceding 8 h, serum
             creatinine level >1.6 mg/dl, platelet count <50, 000/mm3, abnormal coagulation
             studies, or total bilirubin concentration (in mg/dL) > 8 x weight (in kg)),
             chromosomal anomalies, congenital or acquired gastrointestinal anomalies, prior
             episode of necrotizing enterocolitis or intestinal perforation.

             -