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.

Early treatment of PDA that starts within the first 3 days of life using rectal ibuprofen q24h for 3 days, dosages: 20 mg/kg + 10 mg/kg + 10 mg/kg

Early treatment of PDA that starts within the first 3 days of life using intravenous paraceta-mol 15 mg/kg q6h for 3 days

Expectant PDA management is characterized as 'watchful waiting'. No intervention is initiated with the intention to close a PDA unless defi-nitely needed based of the predefined infant's condition.

Expectative PDA management is character-ized as 'watchful waiting'. No intervention is initiated with the intention to close a PDA.

Participants will be evaluated at the end of first and second course, at an expected avarage of 10 days of life

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

Potsiurko S, Dobryanskyy D, Sekretar L. Patent ductus arteriosus, systemic NT-proBNP concentrations and development of bronchopulmonary dysplasia in very preterm infants: retrospective data analysis from a randomized controlled trial. BMC Pediatr. 2021 Jun 19;21(1):286. doi: 10.1186/s12887-021-02750-9.