Introduction Ventilator-associated pneumonia (VAP) is the most common healthcare-associated infection in critically ill patients. Prior studies suggest that probiotics may reduce VAP and other infections in critically ill patients; however, most previous randomised trials were small, single centre studies. The Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT) aims to determine the impact of the probiotic Lactobacillus rhamnosus GG on VAP and other clinically important outcomes in critically ill adults.
Methods PROSPECT is a multicentre, concealed, randomised, stratified, blinded, controlled trial in patients ≥18 years old, anticipated to be mechanically ventilated ≥72 hours, in intensive care units (ICUs) in Canada, the USA and Saudi Arabia. Patients receive either 1×1010 colony forming units of L. rhamnosus GG twice daily or an identical appearing placebo. Those at increased risk of probiotic infection are excluded. The primary outcome is VAP. Secondary outcomes are other ICU-acquired infections including Clostridioides difficile infection, diarrhoea (including antibiotic-associated diarrhoea), antimicrobial use, ICU and hospital length of stay and mortality. The planned sample size of 2650 patients is based on an estimated 15% VAP rate and will provide 80% power to detect a 25% relative risk reduction.
Ethics and dissemination This protocol and statistical analysis plan outlines the methodology, primary and secondary analyses, sensitivity analyses and subgroup analyses. PROSPECT is approved by Health Canada (#9427-M1133-45C), the research ethics boards of all participating hospitals and Public Health Ontario. Results will be disseminated via academic channels (peer reviewed journal publications, professional healthcare fora including international conferences) and conventional and social media. The results of PROSPECT will inform practice guidelines worldwide.
Trialregistration number NCT02462590; Pre-results.
- critically ill
- intensive care
- ventilator-associated pneumonia
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
Statistics from Altmetric.com
Contributors Concept and design: JJ, DH-A, LTh, DJC. Acquisition, analysis or interpretation of data: JJ, DH-A, LT, MM, JM, FL, EHD, NZ, DL, MS, DJC. Drafting of the manuscript: JJ, DH-A, LT, DJC. Critical revision of the manuscript for important intellectual content: everyone. Statistical analysis: DH-A (Trial Biostatistician), LT (Senior Biostatistician), DL, MS. Obtained funding: everyone. Administrative, technical or material support: DH-A, EHD, NZ, LT, DL, MS. JJ and DJC as co-principal investigators take responsibility for the integrity of the data.
Funding This work was funded by the Canadian Institutes of Health Research, Canadian Frailty Network, Physician Services Incorporated, Hamilton Academic Health Sciences Organization and Academic Medical Organization of Southwestern Ontario, as well as St. Joseph’s Healthcare Hamilton and McMaster University. iHealth is providing the blinded study product. FL is a recipient of a Research Career Award from the Fonds de la recherche du Québec-Santé. MS holds a Canada Research Chair in Interdisciplinary Microbiome Research. DJC holds a Canada Research Chair in Knowledge Translation in Critical Care.
Competing interests None declared.
Ethics approval Hamilton Integrated Research Ethics Board REB# 15-322.
Provenance and peer review Not commissioned; externally peer reviewed.
Patient consent for publication Next of kin consent obtained.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.