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Update of the Preventive Antibiotics in Stroke Study (PASS): statistical analysis plan.

Westendorp WF, Vermeij JD, Dippel DW, Dijkgraaf MG, van der Poll T, Prins JM, Vermeij FH, Roos YB, Brouwer MC, Zwinderman AH, van de Beek D, Nederkoorn PJ - Trials (2014)

Bottom Line: 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).Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Academic Medical Center, P,O, Box 22660, 1100 DD Amsterdam, the Netherlands. d.vandebeek@amc.uva.nl.

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.

Trial registration: Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.

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Related in: MedlinePlus

Diagnosis of pneumonia.
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Fig2: Diagnosis of pneumonia.

Mentions: The total number of patients diagnosed with one or more infection(s) during hospital admission will be reported, as well as the total number of infections. Infections will be reported according to subtypes pneumonia, urinary tract infection and other infection. Infection will be assessed in two ways. First, the infection will be diagnosed in the clinical setting by the treating physician and registered as pneumonia, urinary tract infection or other infection. The clinical diagnosis of infection will be used for the primary analysis. Suspected infections without diagnostics being performed are also recorded and reported as such (for example, in a patient with a palliative care policy). Second, infection will be categorized by two infectious disease specialists who are blinded for treatment allocation, using the modified criteria of the Centers for Disease Control and Prevention (CDC criteria)[12]. For this second categorization, patients with fever, new onset delirium or clinical diagnosis of infection during hospital admission will be reviewed. For this purpose, data on the diagnostic procedures during admission as recorded in the Case Record Form (CRF) will be used. For the diagnosis of pneumonia and urinary tract infection prespecified algorithms will be used based on the CDC-criteria (Figures 2 and3). Patients with a positive blood culture or a positive culture from the presumed site of infection, other than the lungs or urine, with a clinically relevant pathogen will be diagnosed as ‘other infection.’ Patients will be categorized as having confirmed pneumonia, urinary tract infection, or other infection. Only bacterial infections will be assessed since preventive antibiotic therapy aims to reduce these infections. Infection with Clostridium difficile is reported as a treatment complication. Case definition of this infection is diarrhea plus a positive C. difficile toxin test. Clostridium infection was diagnosed by the treating physician and was reviewed by the expert panel.Figure 2


Update of the Preventive Antibiotics in Stroke Study (PASS): statistical analysis plan.

Westendorp WF, Vermeij JD, Dippel DW, Dijkgraaf MG, van der Poll T, Prins JM, Vermeij FH, Roos YB, Brouwer MC, Zwinderman AH, van de Beek D, Nederkoorn PJ - Trials (2014)

Diagnosis of pneumonia.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4195873&req=5

Fig2: Diagnosis of pneumonia.
Mentions: The total number of patients diagnosed with one or more infection(s) during hospital admission will be reported, as well as the total number of infections. Infections will be reported according to subtypes pneumonia, urinary tract infection and other infection. Infection will be assessed in two ways. First, the infection will be diagnosed in the clinical setting by the treating physician and registered as pneumonia, urinary tract infection or other infection. The clinical diagnosis of infection will be used for the primary analysis. Suspected infections without diagnostics being performed are also recorded and reported as such (for example, in a patient with a palliative care policy). Second, infection will be categorized by two infectious disease specialists who are blinded for treatment allocation, using the modified criteria of the Centers for Disease Control and Prevention (CDC criteria)[12]. For this second categorization, patients with fever, new onset delirium or clinical diagnosis of infection during hospital admission will be reviewed. For this purpose, data on the diagnostic procedures during admission as recorded in the Case Record Form (CRF) will be used. For the diagnosis of pneumonia and urinary tract infection prespecified algorithms will be used based on the CDC-criteria (Figures 2 and3). Patients with a positive blood culture or a positive culture from the presumed site of infection, other than the lungs or urine, with a clinically relevant pathogen will be diagnosed as ‘other infection.’ Patients will be categorized as having confirmed pneumonia, urinary tract infection, or other infection. Only bacterial infections will be assessed since preventive antibiotic therapy aims to reduce these infections. Infection with Clostridium difficile is reported as a treatment complication. Case definition of this infection is diarrhea plus a positive C. difficile toxin test. Clostridium infection was diagnosed by the treating physician and was reviewed by the expert panel.Figure 2

Bottom Line: 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).Complications of treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs) are reported as safety outcomes.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Academic Medical Center, P,O, Box 22660, 1100 DD Amsterdam, the Netherlands. d.vandebeek@amc.uva.nl.

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.

Trial registration: Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010.

Show MeSH
Related in: MedlinePlus