| Sumario: | QuestionDoes early prophylactic treatment for patent ductus arteriosus with an appropriate dose of acetaminophen (paracetamol) increase survival without serious morbidity in preterm infants of 23 to 26 weeks of gestation?FindingsIn this randomized clinical trial among 778 preterm infants, early prophylactic treatment with acetaminophen did not increase survival without severe morbidity at 36 weeks' postmenstrual age, despite accelerated closure of the ductus arteriosus. This treatment was associated with an increased rate of cholestasis.MeaningProphylactic treatment for patent ductus arteriosus with acetaminophen should not be recommended in very preterm infants. ImportanceControversies persist about management of the ductus arteriosus by nonsteroidal anti-inflammatory drugs in extremely preterm infants. Acetaminophen (paracetamol) appears to be a promising alternative with possibly fewer adverse effects.ObjectiveTo evaluate whether prophylactic intravenous acetaminophen started within 12 hours of birth increases survival without neonatal severe morbidities at 36 weeks' postmenstrual age.Design, Setting, and ParticipantsA double-blind, randomized, placebo-controlled clinical trial was conducted among preterm infants born between 23 weeks 0 days and 28 weeks 6 days of gestation in 43 neonatal intensive care units of 14 European countries between October 2020 (October 2021 for infants born at 23-26 weeks' gestation, after the phase 2 study identified the optimal dose of acetaminophen) and April 2024. Data analysis was conducted from January to June 2025.InterventionIn the acetaminophen group, patients born at 27 to 28 weeks' gestation received a 20-mg/kg loading dose of acetaminophen followed by 7.5 mg/kg every 6 hours for 5 days, and patients born at 23 to 26 weeks' gestation received a 25-mg/kg loading dose of acetaminophen followed by 10 mg/kg every 6 hours for 5 days. In the placebo group, isotonic sodium chloride was administered.Main Outcomes and MeasuresThe primary outcome was survival without neonatal morbidity evaluated at 36 weeks' postmenstrual age. The secondary exploratory outcome was ductus arteriosus closure, assessed by echocardiography on day 7.ResultsA total of 778 patients (median [IQR] gestational age, 26 [25-27] weeks; 375 [48.2%] female) were included in the study, with 391 in the acetaminophen group and 387 in the placebo group. Survival without severe morbidities at 36 weeks' postmenstrual age occurred in 259 infants (66.2%) in the acetaminophen group and 246 (63.6%) in the placebo group (absolute risk difference [ARD], 2.7 [95% CI, -4.0 to 9.3] percentage points; relative risk [RR], 1.04 [95% CI, 0.94 to 1.16]). The ductus arteriosus was considered closed on day 7 in 264 of 371 infants (71.2%) assigned to acetaminophen and 191 of 366 infants (52.2%) assigned to placebo (ARD, 19.0 [95% CI, 12.0 to 25.7] percentage points; RR, 1.36 [95% CI, 1.21 to 1.53]). In the safety analysis, adverse events were not different except for a higher cholestasis rate in the acetaminophen group (25 of 392 infants [6.4%]) vs the placebo group (10 of 386 infants [2.6%]) (ARD, 3.8 [95% CI, 0.9 to 6.9]) percentage points.Conclusions and RelevanceThis study found that prophylactic acetaminophen treatment for patent ductus arteriosus did not increase survival without neonatal morbidities.Trial RegistrationClinicalTrials.gov Identifier: NCT04459117 This randomized clinical trial evaluates whether prophylactic intravenous acetaminophen started within 12 hours of birth, compared with placebo, for patent arteriosus ductus increases survival without neonatal severe morbidities at 36 weeks' postmenstrual age.
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