ArticlesThe Preventive Antibiotics in Stroke Study (PASS): a pragmatic randomised open-label masked endpoint clinical trial
Introduction
Infection is a common complication in the acute phase after stroke.1 In a meta-analysis of 87 studies, the pooled infection rate after stroke was 30%,2 most commonly pneumonia and urinary tract infections. About half of pneumonia cases occur within the first 48 h after stroke onset.3 Many studies have shown that the occurrence of infections after stroke is associated with poor functional outcome and mortality,3, 4 although other investigators have reported that infection after stroke is merely a marker of stroke severity without an independent outcome effect when it is treated promptly.5
Five randomised studies have assessed the preventive use of antimicrobials in patients with acute stroke, with conflicting results.6, 7, 8, 9, 10 A Cochrane meta-analysis including 506 patients concluded that although studies differed in populations analysed, type of antimicrobial used, and definition of infection, overall antimicrobial prophylaxis reduced the infection rate from 36% to 22% (relative risk 0·58 [95% CI 0·43–0·79]) without major adverse effects.11 However, whether or not preventive antimicrobials reduce the risk of poor functional outcome after stroke remains uncertain.11 Existing guidelines for management of acute stroke state that preventive use of antibiotics is not indicated because it has not been proven effective.12 We undertook this study to establish whether or not preventive antimicrobial therapy with a third-generation cephalosporin, ceftriaxone, improves functional outcome in patients with acute stroke.
Section snippets
Study design and participants
In this multicentre, prospective, randomised, open-label, masked endpoint trial—the Preventive Antibiotics in Stroke Study (PASS)—we randomly assigned patients from 30 sites, including academic and non-academic medical centres, in the Netherlands in a 1:1 ratio to treatment with ceftriaxone in addition to stroke unit care, or to standard stroke unit care without preventive antimicrobial therapy.
Patients were enrolled by their treating physicians. Patients were eligible for inclusion if they
Results
Between July 6, 2010, and March 23, 2014, 2550 adult patients from 30 Dutch sites were enrolled and randomly assigned in a 1:1 ratio to the two study groups: 1275 patients to receive ceftriaxone and 1275 patients to receive standard stroke unit treatment without ceftriaxone (the control group) (figure 1). 12 patients (seven in the ceftriaxone group and five in the control group) withdrew consent immediately after randomisation, leaving 2538 patients available for the intention-to-treat-analysis
Discussion
Our study did not show improved functional outcome by preventive antimicrobial therapy in patients with acute stroke, nor did it shorten length of hospital stay or reduce in-hospital or follow-up mortality. One possible reason for these findings could be the high-quality care provided at the stroke units participating in the trial. Prophylaxis with ceftriaxone prevented infections and had a favourable safety profile, but was not associated with a shift in the distribution of scores on the mRS.
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