PROSPECT: Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial

This trial is key in the ongoing search for more effective strategies to prevent serious infection during critical illness in the elderly. Probiotics may be an easy-to-use, readily available, inexpensive approach to help reduce infections in older critically ill patients around the world.

Possible Research Results

Anticipated impact of findings: PROSPECT will determine whether a low cost, readily available intervention – probiotics – have any effect reducing the risk of infection in frail critically ill persons. Frailty is an important construct that will be increasingly measured in intensive care unit (ICU) patients, including in the PROSPECT Trial. In the context of critical illness, degree of frailty identifies a vulnerable population at risk for worse outcomes such as rehospitalization and one-year mortality. There is growing interest in screening for frailty in various healthcare settings. Little is known about the reliability of the Clinical Frailty Score (CFS) in the ICU setting. Associated with the PROSPECT Trial, there will be a stand-alone audit which will help to address that gap by characterizing pre-ICU frailty in consecutive heterogeneous patients in two ICUs using the CFS, comparing assessments without and with family input and between a Research Coordinator, Occupational Therapist and the patient.

About the Project

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 ICU found that patients who receive probiotics experience 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, and elderly patients are often excluded from trials in this setting.

VAP is an infection that is associated with morbidity, mortality and substantial cost. Older patients are at particularly high risk for VAP, likely due to their aging immune system. Probiotics are promising in terms of effectiveness and cost-effectiveness for preventing VAP, but studies in critically ill patients have not been well done.

Therefore, whether probiotics can really prevent VAP and other infections is unclear. We completed a pilot study in 14 ICUs in Canada and the United States which showed that a larger trial was feasible. Specifically, we enrolled the target number of patients, of which 40% were =65 years of age; we followed the protocol faithfully, made sure patients didn’t receive additional probiotics and estimated how many patients developed pneumonia.

We are now ready to establish the effects of probiotics in the ICU in a large trial. In critically ill patients who need support by a breathing machine, we will investigate whether oral L. rhamnosus GG (a common probiotic) prevents VAP and other infections. Following informed consent, patients will be randomized to either L. rhamnosus GG group or an identical placebo twice daily, down a feeding tube. We will record VAP, other serious infections such as Clostridium difficile, and overutilization of antibiotics.

Project Team

Principal Investigator:

Deborah Cook, MD, MSc (Epid), FRCPC, DABIM, CCM, CAHS, FRS  — McMaster University

Co-Investigators:

Ian Ball, MD — Western University

Emmanuel Charbonney, MD — Université de Montréal

Laurence Chau, MD — Oakville Trafalger Hospital

Robert Cirone, MD — St. Joseph’s Health Centre

Peter Dodek, MD — University of British Columbia

Martin Girard, MD — Université de Montréal

Eyal Golan, MD — University of Toronto

Rick Hall, MD — Dalhousie University

William Henderson, MD — University of British Columbia

Margaret Herridge, MD — University of Toronto

Jennie Johnstone, MD — Dalla Lana School of Public Health, University of Toronto/Public Health Ontario

Tim Karachi, MD — McMaster University

Kosar Khwaja, MD — McGill University

Arnie Kristof, MD — McGill University

Jim Kutsiogianis, MD — University of Alberta

François Lamontagne, MD — Université de Sherbrooke

François Lauzier, MD — Université Laval

John Marshall, MD — University of Toronto

Lauralyn McIntyre, MD — University of Ottawa

Maureen Meade, MD — McGill University

Sangeeta Mehta, MD — University of Toronto

Andrew Morris, MD — University of Toronto

Daniel Ovakim, MD — University of British Columbia

Joe Pagliarello, MD — University of Ottawa

Brenda Reeve, MD — Brantford General Hospital

Bram Rochwerg, MD — McMaster University

Lehana Thabane, PhD — McMaster University

Gordon Wood, MD — University of British Columbia

Ryan Zarychanski, MD — University of Manitoba/CancerCare Manitoba

Project Contact: Dr. Deborah Cook — debcook@mcmaster.ca

TG 2015-20-P

Key words: critically ill; probiotics; systematic review