No Treatment Versus Oral Ibuprofen Treatment for Patent Ductus Arteriosus in Preterm Infants

Efficacy and Safety of No Treatment Compared With Oral Ibuprofen Treatment for Patent Ductus Arteriosus in Preterm Infants: a Randomized, Double-blind, Placebo-controlled, Non-inferiority Clinical Trial

The purpose of this study is to evaluate the efficacy and safety of no treatment compared with ibuprofen treatment for patent ductus arteriosus in preterm infants. The study hypothesis is that no treatment is not inferior to oral ibuprofen treatment in preterm infants. (non-inferiority study)

This study is a randomized, double-blind, placebo-controlled, non-inferiority clinical trial.

Inclusion Criteria:

1. gestational age of 30 weeks or less or birth weight of 1250 g or less

2. born in Samsung Medical Center

3. confirmed to have hemodynamically significant patent ductus arteriosus (PDA) during day of life (DOL) 5 to 14

4. Definition of hemodynamically significant PDA: ductal size ≥ 1.5 mm with left-to-right shunt (or bidirectional shunt with dominant left-to-right blood flow) on the initial echocardiography plus at least one of clinical criteria.

   • Clinical criteria

     • Respiratory signs, including tachypnea, chest retraction, increased respiratory support, unable to wean respiratory support
     • Physical signs, including a murmur, hyperdynamic precordium or bounding pulses
     • Blood pressure problems, including decreased mean or diastolic pressure or increased pulse pressure
     • Signs of congestive heart failure, including cardiomegaly, hepatomegaly or pulmonary congestion

Exclusion Criteria:

• Mortality within the first 48 hours of life
• Ductal size < 1.5 mm on the initial echocardiography
• Right-to-left shunt or bidirectional shunting with dominant right-to-left shunt through PDA
• congenital anomaly
• bilateral intraventricular hemorrhage of grade 4
• contraindication of ibuprofen (bleeding diasthesis, platelet count 10,000/mm3 or less, serum creatinine 2.0 mg/dL or greater, necrotizing enterocolitis stage 2 or greater