Probiotics: PRevention Of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT): A Feasibility Pilot Trial

This pilot project assessed the feasibility of a large future study in mechanically ventilated intensive care unit (ICU) patients in six ICUs in Ontario, Québec, British Columbia, Minnesota and Missouri. This preliminary pilot trial approach has increased the efficiency and cost effectiveness of many subsequent large-scale studies in the critical care community.

Research Results

Findings: (1) 150 patients were enrolled over 11 months and recruitment was 1.9 patients per month; (2) adherence of study product was 97%, (3) contamination did not occur; no patients received open-label probiotics, and (4) the adjudicated VAP rate was 19%. The PROSPECT Pilot Trial met all four feasibility objectives of timely recruitment, high adherence to protocol, minimal contamination and VAP burden to target. It also helped to refine pharmacy randomization, product preparation, consent documents and case report forms, as well as estimate realistic timelines for completion. The successful Pilot Trial completion led to the PROSPECT Vanguard Phase of 300 patients as of November 2015.

Impact of findings: A definitive trial showing that probiotics are beneficial against VAP will have an expedited translation into practice by nutritionists, pharmacists, nurses, physicians and managers, given the high baseline risk of VAP among elderly critically ill patients. If probiotics help to decrease potentially lethal infections (VAP), we will have fostered globally recognized research to improve the outcomes of frail elderly patients. If probiotics do indeed lower the risk of VAP, clinical benefits will be lower VAP rates and healthcare expenditures due to this potentially lethal clinical problem.

Publications, presentations and webinars

For more information on why this research matters, click the links below:

Families Researchers

About the Project

Several studies have suggested multiple benefits to critically ill patients who receive probiotics in the ICU. Probiotics appear to mitigate infections, which can lead to costly long stays in the ICU and even fatalities. However, whether probiotics are truly helpful is unclear because of the typically small sample sizes and variable study quality to date.

Before a large expensive international study is done to evaluate the true effects of probiotics in critically ill patients, a pilot trial is needed.

The PROSPECT Pilot Trial proved highly instructive to the ongoing search for more effective strategies to prevent serious infection during critical illness. Probiotics may be a simple, easy-to-use, readily available, inexpensive approach to help reduce infection rates in critically ill elderly patients worldwide.

For more details on the project rationale, objectives and research plan, click here.

Project Team

Principal Investigator:

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

Co-Investigators:

Dawn M.E. Bowdish, PhD — McMaster University/Canadian Critical Care Trials Group

Peter Dodek, MD — University of British Columbia/Canadian Critical Care Trials Group

Erick Duan, MD — McMaster University/Canadian Critical Care Trials Group

Eyal Golan, MD — University of Toronto/Canadian Critical Care Trials Group

William Henderson, MD — University of British Columbia/Canadian Critical Care Trials Group

Margaret Herridge, MD — University of Toronto/Canadian Critical Care Trials Group

Daren Heyland, MD, MSc, FRCPC — Queen’s University

Jenny Johnstone, MD, FRCPC — McMaster University

Tim Karachi, MD — McMaster University/Canadian Critical Care Trials Group

Daphnee Lamarche — McMaster University

François Lauzier, MD, MSc — Université Laval

John Marshall, MD, MSc, FRCPC, AGAF — McMaster University

Lauralyn McIntyre, MD — University of Ottawa/Canadian Critical Care Trials Group

Maureen Meade, BSc, MSc, MD — McMaster University

Sangeeta Mehta, MD — University of Toronto/Canadian Critical Care Trials Group

Daniel Ovakim, MD — University of Victoria/Canadian Critical Care Trials Group

Joe Pagliarello, MD — University of Ottawa/Canadian Critical Care Trials Group

Michael G. Surette, PhD — McMaster University/Canadian Critical Care Trials Group

Lehana Thabane, PhD — McMaster University/Canadian Critical Care Trials Group

Paul Wischmeyer, MD, BSc — University of Colorado Hospital

Gordon Wood, MD — University of Victoria/Canadian Critical Care Trials Group

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

CORE 2012-14

Key words: probiotics; pneumonia; prevention; critical care; nosocomial infection; lactobacillus; lung infection

Key Findings For Families

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

Key Findings for Families

150 patients were in the trial over 11 months
Almost all (97.4%) of the researchers followed the study protocol
The ventilator associated pneumonia rate was 19%

Why This Matters

Ventilator associated pneumonia (VAP) can lead to many complications for elderly patients that are critically ill. There is not a single way to prevent VAP and prevention can be poorly done. A simple and inexpensive VAP prevention strategy, probiotics, might lower pneumonia rates but there are no large studies to show definitively how helpful they can be.

About This Study

This was a “pilot study” for a randomized control trial
Adult elderly critically ill patients in Canada and the U.S. were randomized in a blinded trial to the probiotic Lactobacillus rhamnosus GG or placebo, given twice daily by nasogastric tube while they were in the intensive care unit (immunocompromised patients were excluded)
We hypothesized that a larger trial would be feasible, based on four feasibility outcomes: (1) recruitment success in one year; (2) >90% adherence to the probiotic protocol; (3) <5% contamination rate; and (4) an estimated VAP rate >10%

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Researchers

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

Key Findings for Researchers

150 patients were enrolled over 11 months (1.9 patients per month)
Adherence of study protocol was 97.4%
Contamination did not occur – no patients received a dose of open-label probiotic at any time
The adjudicated ventilator associated pneumonia (VAP) rate was 19%

This study provided evidence to support the feasibility for a large trial of probiotics to prevent ventilator associated pneumonia. The results of the larger trial could have the ability to change clinical care.

The success of this pilot trial provides needed support to embark on a large international trial to evaluate the true impact of probiotics on VAP and other infections in critically ill older persons

Why This Study was Needed

VAP presents a high burden of illness and as such is often used as a quality indicator of care in hospitals. Prevention of VAP is not standardized and often poorly done. A simple and inexpensive VAP prevention strategy, the administration of probiotics, has been suggested to lower pneumonia rates. However large, high quality studies are lacking to provide credence to their efficacy.

How This Study Addresses the Gap

Adult elderly critically ill patients in Canada and the U.S. were randomied in a blinded trial to the probiotic Lactobacillus rhamnosus GG or placebo, given twice daily by nasogastric tube while they were in the intensive care unit (immunocompromised patients were excluded)
We hypothesized that a larger trial would be feasible, based on four feasibility outcomes: (1) recruitment success in one year; (2) >90% adherence to the probiotic protocol; (3) <5% contamination rate; and (4) an estimated VAP rate >10%

Future Research

A large PROSPECT Trial is underway to determine the effect of probiotics on serious infections such as pneumonia and Clostridium difficile.

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Publications

Principal Investigator

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

Presentations

Wheeler, K.E., Calce, A., Cook, D.J., Mehta, S., Perreault, M.M., Thiboutot, Z., Guenette, M., Cho, A., Burry, L. (October 28, 2014). Survey of Canadian Intensive Care Unit Pharmacists’ Attitudes, Knowledge, and Use of Probiotics for Patients (Pro-Surve). Canadian Critical Care Forum, Toronto, ON.

Wheeler, K.E., Calce, A., Cook, D.J., Mehta, S., Perreault, M.M., Thiboutot, Z., Guenette, M., Cho, A., Burry, L. (September 23, 2014). Survey of Canadian Intensive Care Unit Pharmacists’ Attitudes, Knowledge, and Use of Probiotics for Patients (Pro-Surve). TechValueNet Meeting, Toronto, ON.

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Rationale

Principal Investigator

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

Rationale: 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 older frail patients have not been well done.

Objectives: This CFN project (n=30 frail elderly subjects) was a sub-study of a larger 150 patient feasibility study. Four goals of the pilot study will be to determine whether we can successfully enroll patients; follow the protocol faithfully; make sure patients don’t receive additional probiotics, and estimate how much pneumonia exists in these patients.

Research plan: Trial conducted in mechanically ventilated ICU patients in 6 ICUs in Ontario, Québec and Colorado. In this pilot trial, we will enroll 30 elderly adults requiring a breathing machine and give them L. rhamnosus GG (common probiotic) into a feeding tube, or a sugar pill (placebo), twice daily.

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