Update on the Preventive Antibiotics in Stroke Study (PASS): a randomised controlled phase 3 clinical trial
- Equal contributors
1 Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands
2 Clinical Research Unit (CRU), Academic Medical Centre, Amsterdam, The Netherlands
3 Department of Neurology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
4 Centre of Infection and Immunity (CINIMA), Academic Medical Centre, Amsterdam, The Netherlands
5 Department of Infectious Diseases, Academic Medical Centre, Amsterdam, The Netherlands
6 Department of Microbiology, Academic Medical Centre, Amsterdam, The Netherlands
7 Department of Neurology, Sint Franciscus Gasthuis, Rotterdam, The Netherlands
8 Department of Neurology, H2.216, Academic Medical Centre, PO box 22660, Amsterdam 1100 DD, The Netherlands
Trials 2014, 15:133 doi:10.1186/1745-6215-15-133Published: 21 April 2014
Stroke is a leading cause of death worldwide. Infections after stroke occur in 30% of stroke patients and are strongly associated with unfavourable outcome. Preventive antibiotic therapy lowers infection rate in patients after stroke, however, the effect of preventive antibiotic treatment on functional outcome after stroke has not yet been investigated.The Preventive Antibiotics in Stroke Study (PASS) is an ongoing, multicentre, prospective, randomised, open-label, blinded end point trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 hours intravenously for four-days, in addition to stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. Aim of the study is to assess whether preventive antibiotic treatment improves functional outcome at three months by preventing infections.
To date, 2,470 patients have been included in PASS. Median stroke severity of the first 2,133 patients (second interim analysis) is 5 (IQR 3 to 9) on the National Institutes of Health Stroke Scale (NIHSS). Due to the PROBE design, no outcome data are available yet. In the initial trial protocol we proposed a dichotomisation of the mRS as primary analysis of outcome and ordinal regression analysis as secondary analysis of primary outcome, requiring a sample size of 3,200 patients. However, ordinal analysis of outcome data is becoming increasingly more common in acute stroke trials, as it increases statistical power. For PASS, funding is insufficient for inclusion of 3,200 patients with the overall inclusion rate of 15 patients per week. Therefore we change the analysis of our primary outcome from dichotomisation to ordinal regression analysis on the mRS. Power analysis showed that with similar assumptions 2,550 patients are needed using ordinal regression analysis. We expect to complete follow-up in June 2014. A full statistical analysis plan will be submitted for publication before treatment allocation will be unblinded.
The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection. In this update, we changed our primary outcome analysis from dichotomisation to ordinal regression analysis.
Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.