Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT): A Feasibility Clinical Trial

NCT01782755 | Completed Phase 2

• 1 other identifier: 28012013
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 14

Brief Summary

Probiotics are commercially available live bacteria thought to have health benefits when ingested. A 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. However, the studies reviewed were small and not 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. The investigators plan to study the feasibility of such a trial in mechanically ventilated ICU patients in 11 ICUs in Ontario, 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 additional probiotics, and estimate how much pneumonia exists in these patients. In a separate substudy, the investigators 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. The investigators plan to enroll 150 adults admitted to ICU and 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. The investigators will record all infections and other important outcomes in the ICU. This study is very important 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.

Conditions

Ventilator Associated Pneumonia (VAP); Other Infections; Antibiotic-Associated Diarrhea; C-Difficile; Duration of Mechanical Ventilation; Length of ICU Stay; Length of Hospital Stay; ICU and Hospital Mortality

Keywords

Probiotics; Ventilator Associated Pneumonia (VAP); Infection; Antibiotic-Associated Diarrhea; C-Difficile

Outcome Measures

Primary Outcomes (1)

• Pilot Trial - Feasibility

  Is it feasible to perform a large RCT in mechanically ventilated critically ill patients to investigate whether orally ingested L. rhamnosus GG prevents VAP, based on successful and timely pilot trial recruitment; high adherence to protocol; minimal contamination; and an acceptable VAP rate?

  90 days

Study Arms (2)

Lactobacillus rhamnosus GG

ACTIVE COMPARATOR

Patients allocated to the intervention group will receive 1x1010 colony forming units (CFU) of Lactobacillus rhamnosus GG (Culturelle, Locin Industries Ltd) in 1 capsule suspended in sterile water, administered through a nasogastric, nasoduodenal, percutaneous gastrostomy or percutaneous jejunal tube twice daily while patients are mechanically ventilated until 24 hours of spontaneous breathing. The first dose will be within 48 hours of intubation.

Drug: L. rhamnosus GG - Probiotic

Placebo

PLACEBO COMPARATOR

Patients allocated to the placebo group will receive a capsule identical in appearance to the L. rhamnosus GG capsule, but containing microcrystalline cellulose. The placebo will also be suspended in sterile water and similarly administered twice a day. When suspended in water, the placebo has identical appearance and consistency as the probiotic. The placebo will be prepared by the manufacturer of L. rhamnosus GG, Culturelle, and has been used successfully in a recent RCT in the ICU population

Other: Placebo - Microcrystalline Cellulose

Interventions

L. rhamnosus GG - Probiotic DRUG

Twice daily, patients will receive either 1x1010 colony forming units (CFU) of L. rhamnosus GG (Culturelle, Locin Industries Ltd) in 1 capsule or an identical placebo capsule

Also known as: Culturelle Probiotic

Lactobacillus rhamnosus GG

Placebo - Microcrystalline Cellulose OTHER

Placebo capsule, twice daily (containing Microcrystalline Cellulose)

Also known as: Placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years old in the ICU;
• Mechanically ventilated with anticipated ventilation of ≥72 hours at enrolment.

You may not qualify if:

• Mechanical ventilation exceeding 72 hours at time of screening.
• Increased risk of iatrogenic probiotic infection including specific immunocompromised populations (HIV \<200 CD4 cells/μL, chronic immunosuppressive medications, prior organ or hematological transplant, neutropenia (absolute neutrophil count \<500).
• Increased risk for endovascular infection (history of rheumatic heart disease, congenital heart defect, mechanical valves, endocarditis, endovascular grafts, permanent endovascular devices such as permanent (not short-term) hemodialysis catheters, pacemakers or defibrillators).
• Mucosal gastrointestinal tract defects (gastroesophageal or intestinal injury, including active bleeding), surgery of the esophagus, stomach, small or large bowel, liver, gallbladder, hepatobiliary tree, spleen, or pancreas within 72 hours, suspected or documented ischemic gut and severe acute pancreatitis.
• Strict contraindication or inability to receive enteral medications.
• Pregnancy.
• Intent to withdraw advanced life support.
• Enrolment in this or an ongoing related trial.

Sponsors & Collaborators

• McMaster University: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Technology Evaluation in the Elderly Network (TVN): collaborator
• Physician's Services Incorporated (PSI): collaborator
• Hamilton Academy of Health Science Research Organization (HAHSO): collaborator

Study Sites (14)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

St. John's Mercy Medical Center

St Louis, Missouri, 63141, United States

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

St. Paul's Hospital

Vancouver, British Columbia, V6Z1Y6, Canada

Location

Vancouver Island Health Authority

Victoria, British Columbia, V8R 1J8, Canada

Location

Hamilton Health Science - Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

St Joseph's Healthcare Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Hamilton Health Science - Juravinski Hospital

Hamilton, Ontario, L8V 1C3, Canada

Location

Ottawa Hospital Research Institute - Civic Campus

Ottawa, Ontario, K1H 8G7, Canada

Location

Ottawa Research Institute - General Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

St Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Mount Sinai Hospital

Toronto, Ontario, M5G 1X5, Canada

Location

University Health Network - Toronto Western Hospital

Toronto, Ontario, Canada

Location

Hopital de l'Enfant Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

Related Publications (5)

• Lau VI, Xie F, Fowler RA, Rochwerg B, Johnstone J, Lauzier F, Marshall JC, Basmaji J, Henderson W, Khwaja K, Loubani O, Niven DJ, Zarychanski R, Arabi YM, Cartin-Ceba R, Thabane L, Heels-Ansdell D, Cook DJ. Health economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): a cost-effectiveness analysis. Can J Anaesth. 2022 Dec;69(12):1515-1526. doi: 10.1007/s12630-022-02335-9. Epub 2022 Oct 26.

  PMID: 36289153 DERIVED

• Lau VI, Cook DJ, Fowler R, Rochwerg B, Johnstone J, Lauzier F, Marshall JC, Basmaji J, Heels-Ansdell D, Thabane L, Xie F; PROSPECT Collaborators. Economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): study protocol. BMJ Open. 2020 Jun 28;10(6):e036047. doi: 10.1136/bmjopen-2019-036047.

  PMID: 32595159 DERIVED

• Lamarche D, Johnstone J, Zytaruk N, Clarke F, Hand L, Loukov D, Szamosi JC, Rossi L, Schenck LP, Verschoor CP, McDonald E, Meade MO, Marshall JC, Bowdish DME, Karachi T, Heels-Ansdell D, Cook DJ, Surette MG; PROSPECT Investigators; Canadian Critical Care Trials Group; Canadian Critical Care Translational Biology Group. Microbial dysbiosis and mortality during mechanical ventilation: a prospective observational study. Respir Res. 2018 Dec 7;19(1):245. doi: 10.1186/s12931-018-0950-5.

  PMID: 30526610 DERIVED

• Johnstone J, Meade M, Marshall J, Heyland DK, Surette MG, Bowdish DM, Lauzier F, Thebane L, Cook DJ; PROSPECT Investigators and the Canadian Critical Care Trials Group. Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: protocol for a feasibility randomized pilot trial. Pilot Feasibility Stud. 2015 May 24;1:19. doi: 10.1186/s40814-015-0013-3. eCollection 2015.

  PMID: 27965798 DERIVED

• Cook DJ, Johnstone J, Marshall JC, Lauzier F, Thabane L, Mehta S, Dodek PM, McIntyre L, Pagliarello J, Henderson W, Taylor RW, Cartin-Ceba R, Golan E, Herridge M, Wood G, Ovakim D, Karachi T, Surette MG, Bowdish DM, Lamarche D, Verschoor CP, Duan EH, Heels-Ansdell D, Arabi Y, Meade M; PROSPECT Investigators and the Canadian Critical Care Trials Group. Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: a pilot trial. Trials. 2016 Aug 2;17:377. doi: 10.1186/s13063-016-1495-x.

  PMID: 27480757 DERIVED

Related Links

• PROSPECT Trial

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Infections

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Deborah J Cook, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2013
• First Posted: February 4, 2013
• Study Start: October 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: January 1, 2015
• Last Updated: August 28, 2019

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (12); US (2)