Trial status

Initially, 15 participating centres started recruitment between December 2016 and April 2019, two additional centres started recruitment between August 2019 and May 2020. In another centre no patient was found to be eligible.

During the study we experienced lower inclusion rates than expected, both due to a lower rate of parental informed consent, but also a lower rate of PDA > 1.5mm than anticipated. As the funding by ZonMw stopped on 15 December 2020 and the conflicting DOXA Trial (Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT04430790","term_id":"NCT04430790"}}NCT04430790) started recruitment, enrollment was ended when in total 273 (48.4% of projected inclusion) patients were randomized (early pharmacological treatment n=137; expectant management n=136). The power calculation was based on data from 2008-2012, which might not represent current data. Even with the actual number of inclusions the BeNeDuctus Trial is the 3^rd largest RCT investigating PDA treatment since 2000 with regard to the study population. As the first two largest studies investigated prophylactic treatment [29, 30], this study is in fact the largest RCT investigating early pharmacological treatment.

The last patient is included on 5 December 2020. The last assessment of the primary outcome will be completed in March 2021. The last follow-up at 2 years corrected age is expected around March 2023. The database for the short-term outcome measurements will be locked only after data has been monitored and this SAP has been submitted for publication in a peer-reviewed journal. The long-term outcome measurements will be locked mid-2023 after monitoring of the data.