Early Treatment Versus Expectant Management of PDA in Preterm Infants

Lviv National Medical University (LNMU)

Status: Completed

Conditions: Patent Ductus Arteriosus

Treatments: Drug: Paracetamol; Drug: Ibuprofen; Other: Expectant Management

Study type: Interventional

Funder types: Other

Identifiers

NCT03860428

04011994

Details and patient eligibility

About

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.

Enrollment: 208 patients

Sex: All

Ages: Under 3 days old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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208 participants in 3 patient groups

Rectal ibuprofen

Active Comparator group

Description:

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

Treatment:

Drug: Ibuprofen

Intravenous paracetamol

Active Comparator group

Description:

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

Treatment:

Drug: Paracetamol

Expectant Treatment

Sham Comparator group

Description:

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.

Treatment:

Other: Expectant Management