Frailty and the risk of ICU-acquired infections in a randomised trial: a protocol and statistical analysis plan

INTRODUCTION: Dysregulated immunity may account for an increased risk of infection and other adverse outcomes among frail hospitalised persons. The primary objective of this study is to examine whether baseline frailty is associated with the risk of developing ventilator-associated pneumonia (VAP) or other intensive care unit (ICU)-acquired infections among invasively ventilated adults. Additional objectives are to examine the relationship between frailty and hospital length of stay, discharge to a long-term care facility and vital status. We hypothesise that persons with frailty compared with others would have an increased risk of VAP and other infections, a longer hospital stay, higher probability of discharge to a long-term care facility and higher mortality. METHODS AND ANALYSIS: This is a preplanned secondary analysis of the PROSPECT trial (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) which enrolled patients across 44 ICUs in three countries. We will use Cox proportional hazards regression analysis to assess the association of frailty with the clinical outcomes of interest, adjusting for other baseline variables. Baseline demographic and descriptive outcome data will be reported using descriptive statistics. Regression results will be presented as adjusted HRs or ORs with 95% CIs for the associations of each independent variable with the primary, secondary and tertiary outcomes. ETHICS AND DISSEMINATION: Participating hospital research ethics board approved the PROSPECT trial and data collection. The protocol for this study was approved by the Hamilton Integrated Research Ethics Board on 20 August 2015 (Project ID:19128). This study will identify whether frailty is associated with risk of VAP and other healthcare-associated infections in invasively ventilated patients, adjusted for other baseline factors. Results may be useful to patients, their caregivers, clinicians and the design of future research. Findings will be disseminated to investigators at a meeting of the Canadian Critical Care Trials Group. We will present study results at an international conference in the fields of critical care and infectious diseases, to coincide with or precede open-access peer-review publication. To aid knowledge dissemination, we will use a variety of formats. For example, for traditional and social media, we will create two different visual abstracts and infographics of our results suitable to share on clinician-facing and public-facing platforms. TRIAL REGISTRATION NUMBER: NCT02462590.