Background and importance Haemodynamically significant patent ductus arteriosus (hsPDA) is a common cause of morbidity and mortality in preterm infants. Currently, the first-line therapy for hsPDA is ibuprofen, but this treatment has potentially life-threatening side effects. Paracetamol has been proposed as an alternative to ibuprofen, but there is still insufficient clinical evidence to make a standard recommendation.
Aim and objectives To evaluate the efficacy and safety of the standard treatment of hsPDA with ibuprofen versus paracetamol in the closure of hsPDA.
Material and methods Non-inferiority, randomised, multicentre, double-blind clinical trial was designed to evaluate the efficacy and safety of intravenous (IV) paracetamol versus IV ibuprofen in preterm patients with a gestational age (GA) ≤30 weeks diagnosed with hsPDA in four Spanish hospitals. Patients were randomized 1:1 to 10 mg/kg ibuprofen followed by 5 mg/kg at 24 and 48 hours or 15 mg/kg paracetamol every 6 hours for 3 days. If ductus size was >1 mm after the end of the 3-day course of the assigned treatment, another 3-day course of the same treatment was administered. If not, efficacy, ibuprofen and/or surgical closure were evaluated. The primary endpoint was ductus closure after the first treatment course.
Results The clinical trial is currently ongoing. The results presented correspond to an interim analysis with the objective of evaluating possible relevant safety warnings. A total of 91 patients have been recruited (approximately one-third of the scheduled recruitment). The populations of both groups have been comparable, with a mean GA of 26 weeks. For the main variable, ductus clousure after the first treatment course, an intention-to-treat analysis revealed no statistically significant differences between the groups (62.8% vs 42.2%, p=0.053). Applying the random stop method to assess the need to continue or stop the study, a p value <0.978 was obtained, the limit for assuming a lack of power. Likewise, no differences were found in the main safety variables.
Conclusion and relevance Given the data obtained in the intermediate analysis, it is essential to continue with the planned recruitment. At the moment, with the results of this analysis and the previous literature, it is not yet possible to establish a clear recommendation on the use of paracetamol in hsPDA.
Conflict of interest No conflict of interest
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