Project Overview

Probiotics are commercially available live bacteria thought to have health benefits when ingested.  Studies have shown that probiotics may reduce ventilator associated pneumonia (VAP) by 25%. , and reduce 18% of all other infections, and 65% of Clostridium difficile infections. However, previous studies were small and potentially biased; therefore, whether probiotics are truly helpful remains unclear.  With TVN funding, we recently completed a randomized controlled pilot trial in critically ill patients who need a breathing machine in 14 intensive care units (ICUs) to test the feasibility of doing a larger trial designed to determine whether probiotics prevent VAP. This feasibility study achieved all 4 a priori feasibility objectives: 1) 150 patients were enrolled over 11 months; recruitment was 1.9 patients per month among actively recruiting centers; 2) adherence of study product was 97.4%; only 2.6% of doses prescribed were not received; 3) contamination did not occur; no patients received a dose of open-label probiotic at any time and 4) the adjudicated VAP rate was 19%. We are now proceeding to investigate whether L. rhamnosus GG (LGG, a common probiotic) prevents VAP and other infectious outcomes. We will enroll 2650 patients overall and based upon the pilot and Vanguard results approximately 40% of the patient will be adults ≥65 years old across 38 centers. Patients will receive either LGG or a placebo, twice daily while in the ICU.

Older persons developing critical illness are at extremely high risk for acquiring infections and VAP is among the most serious. Probiotics are readily available, inexpensive, and have a favourable safety profile; indeed, recent publications suggest that probiotics are one of the most cost-effective strategies for preventing VAP.  However, due to the limitations of prior studies, current data do not yet truly support their widespread use.  The PROSPECT Trial is ready to launch, in collaboration with the  Canadian Critical Care Trials Group, to determine the utility of probiotics in practice for older patients with critical illness.

Milestones will include a start-up PROSPECT Investigator meeting in Halifax in June 2016, and Montreal in November 2016.  Progress will be discussed at PROSPECT presentations in association with the 3 annual Canadian Critical Care Trials Group meetings in Calgary, Toronto and peripatetically in eastern Canada.  Additional milestones include 2 interim analyses at one-third and two-thirds of patient enrolment, and the final analysis.

Deliverables will include successful trial completion on time and on budget, knowledge transfer through conference presentations, peer-reviewed abstracts and manuscript publications, and submission of results to the Canadian VAP Prevention Guideline Committee for incorporation into clinical recommendations for practitioners around the world.