vinayakneo

The biggest problem with BeNeDuctus and Baby Oscar is the patient selection. The hemodynamically significant PDA definition based on PDA characteristics alone (Diameter > 1.5 mm and flow characteristics) may have high sensitivity but poor specificity. Various PDA scores are available which are better at defining the HSPDA than PDA characteristics alone. Interestingly they had more echo-based criteria before open-label use than they used to define HSPDA. I wonder why they did not use those in the first place. It implies that they may have treated some non-HSPDAs with Ibuprofen when it was not needed. No matter how well their trial was designed after patient selection, the trial outcomes might not be true due to selection bias. EBNEO commentary authors have not covered this part. In addition just like CLD, there has been a significant shift in HSPDA over the past 2 decades. HSPDA is a major issue in < 26 weeks infants and most of the 27 or 28 weeks infants can close their PDAs very well on their own without significant intervention. They rarely exhibit significant CLD purely from HSPDAs which was one of the main primary outcomes in both trials. In both BeNeDuctus and Baby Oscar trials, 50% of the patients were > 26 weeks at birth. (In BeNeDuctus infants < 26 weeks were 64/136 in the Ibuprofen group vs 55/137 in the expectant group and in BabyOscar had 118/324 in ibuprofen vs 125/322 in the expectant group). Also, 30% open use of Ibuprofen in the control arm alters the outcomes of the trial significantly. My take is that these trials show us that the current medical management (Ibuprofen) for PDA may be suboptimal and we have to look at better ways of treating it. A trial of PDA treatment with catheter-guided device closure (Picolo) against a placebo may answer this question. Due to the 50-60% efficacy of NSAIDs, it will be hard to recruit many patients within 1st week of life. It will be a herculean task to get consent from families and convince physicians to do catheter ligation as the first intervention for HSPDA. Till then, we will continue to debate 'how to treat PDAs' for the next few decades.