WIP 69 - Extended prophylactic paracetamol treatment for ductal closure in extremely premature infants: a randomized clinical trial.

Poster Number: WIP 69
Publication Number: WIP 69.2448

Background: In extremely low gestational age ( < 28wk, ELGA) infants, ductus arteriosus frequently fails to close, leading to patent ductus arteriosus (PDA). Symptomatic PDA has been associated with increased morbidities and mortality. It has been treated medically with prostaglandin inhibitors, but their efficacy in ELGA infants has remained poor, and associated with adverse effects (AE). In our previous randomized clinical trial (RCT) of very preterm infants ( < 32wk), paracetamol medication for 4d, vs. placebo, accelerated early ductal closure with no AEs detected (Härkin 2016). However, scarce data on paracetamol dosage for early ductal closure in ELGA infants are available. In a previous cohort study, the median duration of paracetamol in ELGA infants was 9d and it was well tolerated (Juujärvi 2018). Thus, we hypothesized that the increase in the duration of the treatment would be safe and potentially effective.

Objective: To study the efficacy and safety of 9d early, prophylactic paracetamol treatment for ductal closure in ELGA infants.

Design/Methods: In the present phase 2 RCT, ELGA infants' PARAcetamol Study (PARAS; EudraCT 2018-000566-11, NCT03641209), infants were randomly assigned to intravenous paracetamol (loading dose 20mg/kg, maintenance 7.5mg/kg q6h) or placebo (0.45% NaCl) within 96h from birth for 9d. With 20% power and 5% alpha-error, and with the ductal closure time assumed to shorten from 35.8 to 7.4d, the sample size was calculated n=40 (20/group). All parents gave written informed consent. Multiple cardiac ultrasound scans of ductal calibers by neonatologists and other measurements were performed before the 1st dose until closure, or 1d after the last dose. Safety analysis will include the numbers of AEs, serious AEs, and neonatal outcomes.

Recruitment lasted from Sep 2018 to Oct 2023 (n=40). Randomization will be revealed when the last patient leaves the intensive care unit. We expect to complete the data analyses in the beginning of 2024.