PAS 2108 No4: you little SCAMP!

In the part of England where I was born and spent the early years of my life, and where my parents are from, the Manchester region, ‘scamp’ was a sort of affectionate term for a young child who had done something wrong, so if a toddler emptied a milk bottle on the floor by accident they would be referred to as ‘a little scamp’.

https://upload.wikimedia.org/wikipedia/en/4/48/The_Scamp_%281957_film%29.jpg This 1950’s English movie was a lot darker than that.

The SCAMP study was also small and irritating!

It was registered at NCT01994993

I am still looking to see if the protocol was published anywhere..

This was a multicenter randomized controlled trial to answer a really important question in neonatology. What are the appropriate antibiotics in complicated intra-abdominal infections? (Disclaimer, we were part of this trial, and Julie Autmizguine of our center was one of the investigators).

This was a difficult trial to do; when an infant <34 weeks gestational age and <121 days postnatal age was eligible, with either necrotizing enterocolitis with pneumatosis, or a perforation or peritonitis associated with other diagnoses, they were randomized to one of 3 antibiotic regimens; ampicillin, gentamicin, and metronidazole (group 1); ampicillin, gentamicin, and clindamycin (group 2); or piperacillin-tazobactam and gentamicin (group 3). The study was registered at NCT01994993

Part of the rationale was Julie Autmizugine’s observational study that seemed to show an increase in intestinal stenosis among infants with NEC who received anaerobic coverage, which may have been due to the fact that mortality was a bit lower, so there were a few more babies alive to develop strictures (or maybe not, it was an observational study after all).

Of the 182 patients reported in the abstract, 2/3 were randomized, the others were a simultaneous observational cohort. Mortality was similar between groups, but differed by a maximum of 3% (between about 8 and about 11%), that is not a big numeric difference, but is a large enough difference to influence antibiotic choice if it is real.

Treatment success was defined as being alive, with a negative blood culture and “a clinical cure score >4” which I can’t see defined in the abstract, nor is it mentioned in the registration document, and, as I said, I can’t find a published protocol. After a bit of googling around I did find the clinical cure score in an online pdf of a presentation somewhere by the presenting author. Each element of the score was evaluated and assigned a score of 0 or 1. So if you were extubated, with a lower FiO2, not on dopamine, not oliguric or acidotic, and seizure free, you would score 6.

This was adjudicated 30 days after antibiotic treatment, and was similar between groups, 73%, 83% and 74% respectively had a succesful treatment because they were alive and scored less than 4. The group with the highest success though, had the highest mortality… which brings me back to, yes, composite outcomes, and what a problem they are!

If I work this out, in the 1st group, 92% were alive, but another 20% had cure scores of 4 or less, which surprises me 30 days after the antibiotics. Still being ventilated and having a higher FiO2 I would think happen frequently, but, being on inotropes or oliguric or acidotic or having seizures, to have so many with at least 2 of those is unexpected.

In the second group, there were 89% alive and another 6% with a low cure score. This is again a complicated study, only partially randomized, and unblinded. There were a lot of babies who had pharmacokinetics, and a lot of important data will come out of the trial over the next years, I think. And a design for future larger better trials, I hope. This is one of the first trials to address this difficult subject, lets hope we can move forward from this.

 

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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