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  • Canadian Critical Care Trials Group
    The Canadian Critical Care Trials Group (CCCTG) is a national organization of more than 300 individuals with research interests in the management of the critically ill patient.
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Programs

Principal Investigator(s)

Coordinator(s)

Nicole Zytaruk et France Clarke

Status

Enrolling

PROSPECT — Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial






Research Question

Is it feasible to perform a large RCT in critically ill patients to test whether oral L. rhamnosus GG prevents ventilator-associated-pneumonia (VAP), based on timely recruitment; high protocol adherence; minimal contamination; and an acceptable VAP rate? We hypothesize that the larger trial will be feasible.

Background

As the commonest ICU-acquired infection, the burden of VAP is high in terms of morbidity, mortality and costs. More effective VAP prevention strategies are needed, and probiotics are an innovative promising strategy. However, small prior trials make their true impact uncertain. Before a large well-designed, multicenter trial is launched, a feasibility trial is necessary. In this PROSPECT Pilot Trial, if all 4 of our feasibility objectives are met regarding recruitment targets, protocol adherence, minimal contamination and estimated VAP rates, we will be well positioned to pursue the full scale trial. A mechanistic substudy will also investigate the microbiologic effects of probiotics on lower respiratory tract and lower GI colonization with potential pathogens, and the effect on endotoxin levels, using endotracheal aspirates, stool and whole-blood samples. This pilot trial is essential before designing and launching a large expensive trial with clinically important endpoints. 

Lay Summary

According to the World Health Organization, probiotics are commercially available live bacteria thought to have health benefits when ingested. Our literature review of probiotic studies in the intensive care unit (ICU) found that in patients who receive probiotics, there is a 25% reduction in lung infection, known as ventilator-associated pneumonia (VAP). There is also an 18% reduction in the chance of developing any infection in the ICU. Although probiotics also seem to reduce antibiotic-associated diarrhea and Clostridium difficile bowel infections in other settings, this has not been properly evaluated in the ICU setting. Studies in critically ill patients have not been well done. Therefore, whether probiotics are really helpful or not is unclear. Before a large carefully performed study is done to evaluate the effects of probiotics in critically ill patients, a pilot trial is needed. We plan to study the feasibility of such a trial in criticallyl ill patients who need the breathing machine, investigating whether orally ingested L. rhamnosus GG (a common probiotic) prevents VAP and other infections. The 4 goals of the pilot study will be to ensure that we can successfully enrol patients; follow the protocol faithfully; make sure patients don't receive too many additional probiotics, and estimate how much pneumonia and other infection develops in these patients. In a separate substudy, we will evaluate the effects of probiotics on lower lung infiltration with potential harmful bacteria, stool bacteria, markers of immunity called cytokines, and markers of infection called endotoxin levels. We plan to enroll adults admitted to the ICU who are receiving mechanical ventilation. Following informed consent, patients will be randomized to either L. rhamnosus GG group or an identical placebo. Twice daily, patients will receive probiotics or placebo in a feeding tube. We will record all infections and other important outcomes in the ICU. This study is key in the ongoing search for more effective strategies to prevent serious infection during critical illness. Probiotics may be an easy-to-use, readily available, inexpensive approach to help future critically ill patients around the world.

LEARN MORE ABOUT PROSPECT
www.prospectpilottrial.com

Co-Investigators

Maureen Meade, Timothy Kirachi, John Marshall, Jan Friedrich, Peter Dodek, Geeta Mehta, François Lauzier, Lauralyn McIntyre, Joe Pagliarello, Bill Henderson, Margaret Herridge

Participating Centers

Click here to download the liste of participating centres.