PAS 2018 No2: let’s STOP-BPD

The STOP-BPD trial was a multicenter trial from Holland, (registered as NTR2768) over 180 babies were randomized to each arm of this trial, they were <30 weeks or less than 1250 g at birth, and were still ventilated at 2 weeks of age.  They had a respiratory index of more than 2 (which you get by multiplying the mean airway pressure by the FiO2). They actually changed the eligibility criteria during the trial as many infants with a respiratory index between 2 and 3.5 (the original criterion) were still developing BPD. A respiratory index of 2.1 therefore would be achieved by having a mean airway pressure of 10 in 21% oxygen, roughly, therefore, anything more than a mean airway pressure of 10 would make you eligible, or lower pressures with higher FiO2.

Infants in the hydrocortisone group received hydrocortisone 5 mg/kg/day Q.I.D for 7 days, followed by 3.75 mg/kg/day T.I.D. for 5 days, then one dose less per day every 5 days. This led to a duration of therapy of 22 days and a cumulative dose of 72.5 mg/kg hydrocortisone. The protocol was published here.

The results, as presented at PAS 2018, showed no difference in the primary outcome, which was survival without BPD. In contrast there were many fewer deaths, 16% vs 24%, and no change in moderate or severe BPD, 65% vs 66% with the hydrocortisone treatment compared to placebo. We don’t have long term neurologic or developmental follow up as yet, but to be honest I am not sure how important that is, if there is an increase in survival. Even if there are more survivors with low Bayley scores, there are more survivors! Also important, survival as reported in the abstract was survival to 36 weeks, they don’t mention survival to discharge which is much more important; with such a big difference in survival to 36 weeks, survival to discharge might well be improved. I don’t remember in the presentation if survival to discharge was reported.

These 2 studies, SAIL and STOP-BPD) illustrate really well the problem with these combined outcomes in neonatal studies. Especially this particular common outcome, combining oxygen needs at 36 weeks PMA with death, I think this is really a big problem.  The two outcomes are not of equivalent value to families, nor to me. What are you supposed to do with those data, to say to parents: “we could start steroids now, but that doesn’t change the probability of your baby surviving to discharge without needing oxygen at 36 weeks. Jacob is more likely to survive if we give him hydrocortisone, however…”

The 2 studies both have a null outcome, but in reality, the STOP-BPD trial intervention appears to be (at least potentially until the peer reviewed publication appears) a major benefit to babies. SAIL is the opposite, a study had a null outcome, but what seems to be a serious negative impact of the intervention. There are other ways of designing and analyzing these trials, analysis of survival as a first step, and then presenting morbidities among survivors would be much more useful for future families. Even profound impairments with limited communication skills, should be separated from mortality, as different families have differing attitudes to survival of the most handicapped infants.

About keithbarrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged , , . Bookmark the permalink.

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