Low dose paracetamol for management of patent ductus arteriosus in very preterm infants: a randomised non-inferiority trial.

OBJECTIVE

To compare the efficacy of low dose-short course intravenous paracetamol with a conventional dose regimen for early targeted closure of patent ductus arteriosus (PDA).

DESIGN

Single-centre, double-blinded, active controlled, randomised non-inferiority trial.

SETTING

Level III neonatal intensive care unit in Western India.

PATIENTS

Preterm infants <30 weeks of gestation requiring mechanical ventilation, or continuous positive airway pressure with FiO ≥0.35 and diagnosed with a haemodynamically significant PDA (hsPDA) at 18-24 hours of postnatal age.

INTERVENTIONS

Low dose (10 mg/kg/dose 6 hourly for 72 hours) versus conventional dose (15 mg/kg/dose 6 hourly for 120 hours) intravenous paracetamol treatment.

MAIN OUTCOME MEASURES

Comparison of the rates of ductal closure at completion of sixth postnatal day, using a prespecified non-inferiority margin of 20%.

RESULTS

A total of 102 infants were enrolled. The median gestational age and birth weight of the included infants were 26.4 weeks and 830 g. At completion of the sixth postnatal day, closure of PDA was achieved in 92% of infants in the low dose group as compared with 94% of those in the standard dose group (risk difference: -1.6%, 95% CI: -11.6% to 8.5%, p=0.38). The rates of rescue therapies, adverse effects and other neonatal morbidities were comparable in both groups.

CONCLUSION

In very preterm infants on significant respiratory support, low dose-short course intravenous paracetamol treatment was non-inferior to a conventional dosing regime of paracetamol for closure of hsPDA in the first week of postnatal age. Larger studies with narrow margins of non-inferiority are required to confirm our findings.

TRIAL REGISTRATION NUMBER

CTRI/2017/10/010012.