Oral Ibuprofen Versus Placebo in Treatment of Patent Ductus Arteriosus (PDA)in Preterm Infants
Condition: Patent Ductus Arteriosus After Premature Birth; Patent Ductus Arteriosus Conservative Management
MeSH terms: Premature Birth; Ductus Arteriosus, Patent
Study type: Interventional
Phase: Phase 2

Summary: 
      The management options of Patent Ductus Arteriosus are still controversial and differ between
      centers. Recently, conservative management has been gaining interest as the evidence of
      benefit from medical treatment in terms of mortality and morbidity is lacking.

      This study will compare oral ibuprofen (the standard treatment) with the conservative
      treatment, in terms of ductal closure and morbidity and mortality at discharge in preterm
      neonates less than 34 weeks.
    

Detailed description: 
      A double-blinded, randomized, placebo-control non-inferiority trial was conducted in the
      neonatal intensive care unit (NICU) of Ain Shams University children's hospital, Cairo,
      Egypt.

      Informed consent was taken from the parents or legal guardians before enrolment, after fully
      explaining to them the nature of the study. The approval of the Research Ethics Committee at
      Ain Shams University was also obtained.

      All preterm neonates less than 34 weeks were assessed in the first 48 hours by clinical and
      echocardiographic examination by a cardiologist to detect PDA and exclude any congenital
      heart disease.

      All neonates meeting the inclusion criteria will be randomized into one of two groups:

      Medical treatment group and Placebo group. Targeted neonatal Echo was repeated after 5 days
      of the start of medical treatment by a neonatologist or a cardiologist to assess PDA closure.

      After 7 days of intervention, open-label is offered to all patients with the option of
      another course for patients in the medical treatment group and Rescue therapy in the Placebo
      group.

      The short-term morbidity is documented.

      Withdrawal and replacement of individual subjects:

        -  The attending physician can decide to withdraw a subject from the study for urgent
           medical reasons. If they wish, parents or caregivers can leave the study at any time for
           any reason.

        -  Infants who are withdrawn from the study will be managed according to NICU Protocols.
    

Intervention name(s): Ibuprofen oral suspension; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The medical treatment group will receive oral Ibuprofen with conservative therapy in the form of fluid restriction, Positive End Expiratory Pressure (PEEP), and/or diuretics
An additional course of Ibuprofen may be offered if there is:
Moderate/Severe PDA on Echocardiography
Prolonged ventilation or Increased ventilatory setting
Prolonged use of inotropes or vasopressors or escalating dose
Another form of treatment may be offered if the patient developed side effects from Ibuprofen; Placebo Group will receive Oral Placebo and Conservative therapy in the form of fluid restriction, PEEP, and/or diuretics
An Open-label option might be offered if there are concerns by attending physicians over the poor patient condition that might be attributed to persistent PDA:
Prolonged Ventilation or Escalating Ventilatory Setting
Prolonged Use Of Inotropes or Vasopressors or escalation of Doses
Rescue therapy in the form of a course of oral ibuprofen may be offered:
After 5 days of recruitment
Moderate/Severe PDA on Echocardiography
Prolonged ventilation or Increased ventilatory setting
Prolonged use of inotropes or vasopressors or escalating dose - Another form of treatment may be offered if the patient developed side effects from Ibuprofen
Other intervention name(s): Active treatment; Conservative
Intervention MeSH terms: Ibuprofen
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment