Update protocol Preventive Antibiotics in Stroke Study (PASS)

Authors

  • Paul J. Nederkoorn,

    Corresponding author
    1. Department of Neurology, H2-216, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    • Correspondence: Paul J. Nederkoorn, Department of Neurology, H2-216, Academic Medical Center, University of Amsterdam, P.O. Box 22660, Amsterdam 1100 DD, The Netherlands.

      E-mail: p.j.nederkoorn@amc.uva.nl

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  • Diederik van de Beek

    1. Department of Neurology, H2-216, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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  • Conflicts of interest: None declared.
  • Funding: This work was supported by the Netherlands Organisation for Health Research and Development (ZonMW): 171002302, and the Netherlands Heart Foundation (Hartstichting): 2009B095.

Dear Editor,

The Preventive Antibiotics in Stroke Study (PASS) is an ongoing, phase III, multicenter, prospective, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke that started in 2010 (ISRCTN-number: 66140176)[1]. Patients presenting with stroke (symptoms less than 24 h) are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for four-days, in addition to stroke-unit care, or standard stroke unit care without preventive antibiotic therapy. The aim of the study is to assess whether preventive antibiotic treatment improves functional outcome at three-months at the modified Rankin Scale (mRS). Currently, more than 2400 patients have been enrolled. In the initial trial protocol we presented a dichotomized analysis of on the mRS (0–2 vs. 3–6) as primary outcome, requiring a sample size of 3200 patients, and a proportional odds model in a secondary analysis of the primary end-point [1]. Blinded for any of the outcomes, we have changed the primary analysis in PASS from dichotomization to ordinal regression on the mRS, enhancing statistical power [2]. A new power analysis showed that with identical assumptions on the clinical effect, using a 0·05 two-sided significance level and 80% study power, 2550 patients are needed. The dichotomized analysis will be the secondary analysis of the primary end-point. We expect to complete our trial in June 2014.

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