Randomized Controlled Trial

. 2016 Aug 2:17:377.

doi: 10.1186/s13063-016-1495-x.

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: a pilot trial

Deborah J Cook^{1

2}, Jennie Johnstone^{3

4

5}, John C Marshall^{6

7}, Francois Lauzier^{8

9

10}, Lehana Thabane¹¹, Sangeeta Mehta^{5

7}, Peter M Dodek^{12

13}, Lauralyn McIntyre¹⁴, Joe Pagliarello¹⁴, William Henderson¹⁵, Robert W Taylor¹⁶, Rodrigo Cartin-Ceba¹⁷, Eyal Golan^{5

7}, Margaret Herridge^{5

7}, Gordon Wood¹⁸, Daniel Ovakim¹⁸, Tim Karachi¹⁹, Michael G Surette¹⁹, Dawn M E Bowdish²⁰, Daphnee Lamarche²¹, Chris P Verschoor²⁰, Erick H Duan¹⁹, Diane Heels-Ansdell¹¹, Yaseen Arabi²², Maureen Meade^{19

11}; PROSPECT Investigators and the Canadian Critical Care Trials Group

Affiliations

¹ Department of Medicine, McMaster University, McMaster Health Sciences Center, Room 2C11, 1200 Main Street W, Hamilton, ON, Canada. debcook@mcmaster.ca.
² Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. debcook@mcmaster.ca.
³ Public Health Ontario, Toronto, ON, Canada.
⁴ St. Joseph's Health Center, Toronto, ON, Canada.
⁵ Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁶ Department of Surgery, University of Toronto, Toronto, ON, Canada.
⁷ Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
⁸ Research Center of the CHU de Québec - Population Health and Optimal Health Practices Research Unit, Université Laval, Quebec City, QC, Canada.
⁹ Department of Medicine, Université Laval, Quebec City, QC, Canada.
¹⁰ Department of Anesthesiology and Critical Care, Université Laval, Quebec City, QC, Canada.
¹¹ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
¹² Division of Critical Care Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, BC, Canada.
¹³ Center for Health Evaluation and Outcome Sciences, St. Paul's Hospital and University of British Columbia, Vancouver, BC, Canada.
¹⁴ Division of Critical Care, University of Ottawa, Ottawa, ON, Canada.
¹⁵ Division of Critical Care Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
¹⁶ Department of Critical Care Medicine, Mercy Hospital, St Louis, MO, USA.
¹⁷ Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁸ Department of Anesthesia & Critical Care, Vancouver Island Health Authority, Victoria, BC, Canada.
¹⁹ Department of Medicine, McMaster University, McMaster Health Sciences Center, Room 2C11, 1200 Main Street W, Hamilton, ON, Canada.
²⁰ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
²¹ Biochemistry and Biomedical Sciences Department, McMaster University, Hamilton, ON, Canada.
²² King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.

PMID: 27480757
PMCID: PMC4970233
DOI: 10.1186/s13063-016-1495-x

Randomized Controlled Trial

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: a pilot trial

Deborah J Cook et al. Trials. 2016.

. 2016 Aug 2:17:377.

doi: 10.1186/s13063-016-1495-x.

Authors

Affiliations

¹ Department of Medicine, McMaster University, McMaster Health Sciences Center, Room 2C11, 1200 Main Street W, Hamilton, ON, Canada. debcook@mcmaster.ca.
² Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada. debcook@mcmaster.ca.
³ Public Health Ontario, Toronto, ON, Canada.
⁴ St. Joseph's Health Center, Toronto, ON, Canada.
⁵ Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁶ Department of Surgery, University of Toronto, Toronto, ON, Canada.
⁷ Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.
⁸ Research Center of the CHU de Québec - Population Health and Optimal Health Practices Research Unit, Université Laval, Quebec City, QC, Canada.
⁹ Department of Medicine, Université Laval, Quebec City, QC, Canada.
¹⁰ Department of Anesthesiology and Critical Care, Université Laval, Quebec City, QC, Canada.
¹¹ Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada.
¹² Division of Critical Care Medicine, St. Paul's Hospital and University of British Columbia, Vancouver, BC, Canada.
¹³ Center for Health Evaluation and Outcome Sciences, St. Paul's Hospital and University of British Columbia, Vancouver, BC, Canada.
¹⁴ Division of Critical Care, University of Ottawa, Ottawa, ON, Canada.
¹⁵ Division of Critical Care Medicine, Vancouver General Hospital, Vancouver, BC, Canada.
¹⁶ Department of Critical Care Medicine, Mercy Hospital, St Louis, MO, USA.
¹⁷ Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
¹⁸ Department of Anesthesia & Critical Care, Vancouver Island Health Authority, Victoria, BC, Canada.
¹⁹ Department of Medicine, McMaster University, McMaster Health Sciences Center, Room 2C11, 1200 Main Street W, Hamilton, ON, Canada.
²⁰ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
²¹ Biochemistry and Biomedical Sciences Department, McMaster University, Hamilton, ON, Canada.
²² King Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.

PMID: 27480757
PMCID: PMC4970233
DOI: 10.1186/s13063-016-1495-x

Abstract

Background: Probiotics are live microorganisms that may confer health benefits when ingested. Randomized trials suggest that probiotics significantly decrease the incidence of ventilator-associated pneumonia (VAP) and the overall incidence of infection in critically ill patients. However, these studies are small, largely single-center, and at risk of bias. The aim of the PROSPECT pilot trial was to determine the feasibility of conducting a larger trial of probiotics to prevent VAP in mechanically ventilated patients in the intensive care unit (ICU).

Methods: In a randomized blinded trial, patients expected to be mechanically ventilated for ≥72 hours were allocated to receive either 1 × 10(10) colony-forming units of Lactobacillus rhamnosus GG or placebo, twice daily. Patients were excluded if they were at increased risk of L. rhamnosus GG infection or had contraindications to enteral medication. Feasibility objectives were: (1) timely recruitment; (2) maximal protocol adherence; (3) minimal contamination; and (4) estimated VAP rate ≥10 %. We also measured other infections, diarrhea, ICU and hospital length of stay, and mortality.

Results: Overall, in 14 centers in Canada and the USA, all feasibility goals were met: (1) 150 patients were randomized in 1 year; (2) protocol adherence was 97 %; (3) no patients received open-label probiotics; and (4) the VAP rate was 19 %. Other infections included: bloodstream infection (19.3 %), urinary tract infections (12.7 %), and skin and soft tissue infections (4.0 %). Diarrhea, defined as Bristol type 6 or 7 stools, occurred in 133 (88.7 %) of patients, the median length of stay in ICU was 12 days (quartile 1 to quartile 3, 7-18 days), and in hospital was 26 days (quartile 1 to quartile 3, 14-44 days); 23 patients (15.3 %) died in the ICU.

Conclusions: The PROSPECT pilot trial supports the feasibility of a larger trial to investigate the effect of L. rhamnosus GG on VAP and other nosocomial infections in critically ill patients.

Trial registration: Clinicaltrials.gov NCT01782755 . Registered on 29 January 2013.

Keywords: Critically ill; Infection; Intensive care; Probiotics.

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Figures

**Fig. 1**
The probiotics in ICU research program. The PROSPECT pilot trial is part of the probiotics in ICU Research Program

**Fig. 2**
Average number of hours spent by the PROSPECT pilot trial research coordinator screening, obtaining consent, and enrolling patients per study day of the trial.

**Fig. 3**
Capsule quality assurance results. The quality control protocol was performed on 34 probiotic capsules used in the PROSPECT pilot trial

See this image and copyright information in PMC

References

1. Joint FAO/WHO Working Group. Guidelines for the evaluation of probiotics in food: report of a joint FAO/WHO working group on drafting guidelines for the evaluation of probiotics in food. http://www.who.int/foodsafety/fs_management/en/probiotic_guidelines.pdf. Accessed 26 Dec 2014.
1. Hao Q, Lu Z, Dong BR, Huang CQ, Wu T. Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev. 2011;9:CD006895. - PubMed
1. Hempel S, Newberry SJ, Maher AR, et al. Probiotics for the prevention and treatment of antibiotic-associated diarrhea: a systematic review and meta-analysis. JAMA. 2012;307:1959–69. doi: 10.1001/jama.2012.3507. - DOI - PubMed
1. Ritchie ML, Romanuk TN. A meta-analysis of probiotic efficacy for gastrointestinal diseases. PLoS One. 2012;7(4):e34938. doi: 10.1371/journal.pone.0034938. - DOI - PMC - PubMed
1. Johnson S, Maziade PJ, McFarland LV, et al. Is primary prevention of Clostridium difficile infection possible with specific probiotics? Int J Infect Dis. 2012;16(11):786–92. doi: 10.1016/j.ijid.2012.06.005. - DOI - PubMed

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Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: a pilot trial

Affiliations

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: a pilot trial

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Miscellaneous