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Editor—I am delighted to find that Van Overmeire et al 1 have acquired evidence to support the view that ibuprofen may be a useful treatment for patent ductus arteriosus (PDA). However, their paper may mislead. Their study suggests that there is no more than a 30% difference in the efficacy of indomethacin and ibuprofen for closing PDA. Unfortunately, a 30% difference is often seen as adequate to prove the superiority of one treatment over another, rather than to demonstrate equality.
Since our original publication,2 we have also acquired data which further support the contention that ibuprofen is a suitable treatment for PDA. Using these data to perform power calculations, we found that a total study number of 380 is required to demonstrate that the difference between the rate of PDA closure with each drug is no greater than 10% at the 5% level with 80% power. Such a result would be of far greater value for clinical purposes.
In order to define precisely the value of indomethacin for closure of PDA, we are currently preparing a multicentre randomised double blind control trial which will have sufficient power to settle this question once and for all. We would be delighted to discuss this further with interested research groups.
Van Overmeire and colleagues respond:
We only showed that in a small number of patients ibuprofen seems to be as efficient as indomethacin in closing PDA by day 3 of life. There is no doubt that, as we pointed out in our paper, a larger number of infants should be studied before definitive conclusions in the equal efficacy of both drugs can be drawn. We believe that although ibuprofen seems to be a promising alternative to indomethacin, its efficacy as well as its side effects should be studied further in controlled trials before it can be used in routine practice.
Since we first started our clinical studies with ibuprofen, about 150 patients have been randomly allocated; the data obtained seem to confirm our earlier reported results.
We are currently running a larger multicentre controlled trial in which we compare, not only the efficacy, but also less frequently occurring side effects. Moreover, many other factors will be studied (haemodynamic, cerebrovascular, circulatory, pharmacological, etc). We believe that ibuprofen remains a promising drug, worthy of study in neonates, and we welcome further discussion about clinical trials and other aspects of the drug from interested research groups.
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