Early Treatment Versus Expectant Management of PDA in Preterm Infants

Randomized Non-inferiority Trial of Early Treatment Versus Expectant Management of Patent Ductus Arteriosus in Preterm Infants

Patent ductus arteriosus (PDA) in very preterm newborns is associated with severe neonatal mor-bidity: intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing en-terocolitis (NEC), retinopathy of prematurity (ROP). Existing methods of management PDA do not reduce the incidence of these diseases. The efficacy of cyclooxygenase inhibitors (COX) which are currently the standard of treatment in extreme preterm infants is about 70-80%. COX inhibitors have significant side effects. On the other hand, surgical ligation of the ductus arteriosus is associated with deterioration due to cardio-pulmonary problems and long-term complications. Paracetamol has been proposed for treatment of hemodynamically significant PDA because it has a different mecha-nism of action compared with COX inhibitors and a better safety profile.

Recently, expectant approach has becoming more popular, although there is not enough evidence to support it.

The objective of this study is to investigate whether in preterm infants, born at a GA less than 32 weeks, with a PDA (diameter > 1.5 mm) at a postnatal age of < 72 h, an expectant management is non-inferior to early treatment with regard to the composite of mortality and/or severe morbidity.

Inclusion Criteria:

• Gestational age < 32 weeks
• Birthweight <1500 g
• Age less than 72 hours
• PDA diameter > 1.5 mm
• Signed informed consent obtained from both parents

Exclusion Criteria:

• Birthweight ≥ 1500 g and/or gestation age ≥ 32 weeks
• Lack of informed consent of the parents
• Congenital heart defect, other than PDA and/or patent foramen ovale (PFO)
• The presence of a clinically apparent hemorrhagic syndrome
• Any intraventricular hemorrhage (IVH) in the first 48 hours or IVH grade 3-4
• A platelet count of < 50,000/mm3
• A serum creatinine concentration of > 110 μmol/L
• Oliguria <1 ml/kg/h
• Suspected/apparent NEC
• Suspected/apparent lung hypoplasia