title: Update of the Preventive Antibiotics in Stroke Study (PASS): statistical analysis plan.
abstract: BACKGROUND
  Infections occur in 30% of stroke patients and are associated with unfavorable outcomes. Preventive antibiotic therapy lowers the infection rate after stroke, but the effect of preventive antibiotic treatment on functional outcome in patients with stroke is unknown. The PASS is a multicenter, prospective, phase three, randomized, open-label, blinded end-point (PROBE) trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 h intravenously for 4 days, in addition to standard stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. The aim of this study is to assess whether preventive antibiotic treatment improves functional outcome at 3 months by preventing infections. This paper presents in detail the statistical analysis plan (SAP) of the Preventive Antibiotics in Stroke Study (PASS) and was submitted while the investigators were still blinded for all outcomes.
  
  
  RESULTS
  The primary outcome is the score on the modified Rankin Scale (mRS), assessed by ordinal logistic regression analysis according to a proportional odds model. Secondary analysis of the primary outcome is the score on the mRS dichotomized as a favorable outcome (mRS 0 to 2) versus unfavorable outcome (mRS 3 to 6). Secondary outcome measures are death rate at discharge and 3 months, infection rate during hospital admission, length of hospital admission, volume of post-stroke care, use of antibiotics during hospital stay, quality-adjusted life years and costs. Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes.
  
  
  CONCLUSIONS
  The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection and will be analyzed according to this pre-specified SAP.
  
  
  BACKGROUND
  Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.
authors.forename: Willeke F
authors.initials: WF
authors.lastname: Westendorp
authors.forename: Jan-Dirk
authors.initials: JD
authors.lastname: Vermeij
authors.forename: Diederik W J
authors.initials: DW
authors.lastname: Dippel
authors.forename: Marcel G W
authors.initials: MG
authors.lastname: Dijkgraaf
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
authors.forename: Frederique H
authors.initials: FH
authors.lastname: Vermeij
authors.forename: Yvo B W E M
authors.initials: YB
authors.lastname: Roos
authors.forename: Matthijs C
authors.initials: MC
authors.lastname: Brouwer
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Department of Neurology, Academic Medical Center, P,O, Box 22660, 1100 DD Amsterdam, the Netherlands. d.vandebeek@amc.uva.nl.
authors.forename: Diederik
authors.initials: D
authors.lastname: van de Beek
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Nederkoorn
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000191:economics; D001424:Bacterial Infections / Q000175:diagnosis / Q000191:economics / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D002443:Ceftriaxone / Q000008:administration & dosage* / Q000191:economics; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D003627:Data Interpretation, Statistical; D004185:Disability Evaluation; D004334:Drug Administration Schedule; D016527:Drug Costs; D017052:Hospital Mortality; D006801:Humans; D007902:Length of Stay; D016015:Logistic Models; D009426:Netherlands; D016017:Odds Ratio; D011446:Prospective Studies; D011788:Quality of Life; D020127:Recovery of Function; D012107:Research Design / Q000706:statistics & numerical data*; D020521:Stroke / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000401:mortality / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D002443:Ceftriaxone