Negative trials are just as important – if not moreso – than positive trials. Without negative trials, well-meaning clinicians continue with unproven and unverified treatments, incurring unnecessary costs and exposing patients to unneeded potential adverse effects.
This prospective trial of 2,550 patients randomized patients post-stroke to four days of prophylactic ceftriaxone versus no treatment, using an open-label, masked endpoint design. The theory – some of the mortality and disability post-stroke may be in excess as result of infectious (primarily respiratory) complications. The fact – no. There was no difference in functional outcome at any modified Rankin Score ordinal cut-off, nor mortality. There were actually not fewer cases of pneumonia in the ceftriaxone group, but urinary tract infections were significantly suppressed. Clostridium difficile infection occurred only in two cases, both in the ceftriaxone group.
As a random aside, the median NIHSS in this trial was 5 – and 37% of patients achieved mRS 0-1. This is rather surprisingly low, considering the SITS-MOST cohort and pooled placebo groups from RCTs with median NIHSS’ ~12 had achieved mRS 0-1 in 38% and 33% of the time, respectively. A window into the lack of generalizability of the thrombolysis RCTs? Perhaps – or just a curiosity.
Oh, but, back to the point – it does not appear to have clinical utility to routine use ceftriaxone as antibiotic prophylaxis after acute ischemic stroke.
“The Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial”
http://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)62456-9.pdf