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Evaluating probiotics for the prevention of ventilator-associated pneumonia: a randomised placebo-controlled multicentre trial protocol and statistical analysis plan for PROSPECT
  1. Jennie Johnstone1,
  2. Diane Heels-Ansdell2,
  3. Lehana Thabane2,
  4. Maureen Meade2,
  5. John Marshall3,
  6. Francois Lauzier4,
  7. Erick Huaileigh Duan5,
  8. Nicole Zytaruk2,
  9. Daphnee Lamarche6,
  10. Michael Surette6,
  11. Deborah J Cook5
  12. for the PROSPECT Investigators and the Canadian Critical Care Trials Group
  1. 1 Public Health Ontario, University of Toronto Dalla Lana School of Public Health, Toronto, Ontario, Canada
  2. 2 Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
  3. 3 Surgery/Critical Care Medicine, St. Michael’s Hospital, Toronto, Ontario, Canada
  4. 4 Critical Care, CHU de Quebec-Universite Laval, Quebec, Quebec, Canada
  5. 5 Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  6. 6 Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
  1. Correspondence to Dr. Jennie Johnstone; Jennie.Johnstone{at}oahpp.ca

Abstract

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
  • infection
  • intensive care
  • probiotics
  • ventilator-associated pneumonia

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Footnotes

  • 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.

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