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

Phase 2

Completed

• Conditions: Other Infections; Antibiotic-Associated Diarrhea; Ventilator Associated Pneumonia (VAP); Duration of Mechanical Ventilation; Length of Hospital Stay; C-Difficile; Length of ICU Stay; ICU and Hospital Mortality
• Interventions: Drug: L. rhamnosus GG - Probiotic; Other: Placebo - Microcrystalline Cellulose

• Registration Number: NCT01782755
• Lead Sponsor: McMaster University

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.

Detailed Description

Background: Probiotics are defined as live microorganisms that may confer health benefits when ingested. Meta-analysis of probiotic trials suggests a 25 % lower ventilator-associated pneumonia (VAP) and 18 % lower infection rates overall when administered to patients in the intensive care unit (ICU). However, prior trials are small, largely single center, and at high risk of bias. Before a large rigorous trial is launched, testing whether probiotics confer benefit, harm, or have no impact, a pilot trial is needed. The aim of the PROSPECT Pilot Trial is to determine the feasibility of performing a larger trial in mechanically ventilated critically ill patients investigating Lactobacillus rhamnosus GG. A priori, we determined that the feasibility of the larger trial would be based on timely recruitment, high protocol adherence, minimal contamination, and an acceptable VAP rate.

Methods/design: Patients ≥18 years old in the ICU who are anticipated to receive mechanical ventilation for ≥72 hours will be included. Patients are excluded if they are at increased risk of probiotic-associated infection, have strict enteral medication contraindications, are pregnant, previously enrolled in a related trial, or are receiving palliative care. Following informed consent, patients are randomized in variable unspecified block sizes in a fixed 1:1 ratio, stratified by ICU, and medical, surgical, or trauma admitting diagnosis. Patients receive 1 × 1010 colony forming units of L. rhamnosus GG (Culturelle, Locin Industries Ltd) or an identical placebo suspended in tap water administered twice daily via nasogastric tube in the ICU. Clinical and research staff, patients, and families are blinded.

Discussion: The primary outcomes for this pilot trial are the following: (1) recruitment success, (2) ≥90 % protocol adherence, (3) ≤5 % contamination, and (4) \~10 % VAP rate. Additional clinical outcomes are VAP, other infections, diarrhea (total, antibiotic associated, and Clostridium difficile), ICU and hospital length of stay, and mortality. The morbidity, mortality, and cost of VAP underscore the need for cost-effective prophylactic interventions. The PROSPECT Pilot Trial is the initial step toward rigorously evaluating whether probiotics decrease nosocomial infections, have no effect, or actually cause infections in critically ill patients.

Trial registration: ClinicalTrials.gov. NCT01782755

Keywords: Critically ill, Intensive care, Probiotics, Infection, Pneumonia

Study Timeline

• Study First Submitted: 2013-01-29
• Study First Submitted QC: 2013-01-31
• Study First Posted: 2013-02-04
• Study Start: 2013-10
• Primary Completion: 2014-08
• Study Completion: 2015-01
• Status Verified: 2016-03
• Last Update Submitted: 2019-08-26
• Last Update Posted: 2019-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lactobacillus rhamnosus GG	L. rhamnosus GG - Probiotic	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.
Placebo	Placebo - Microcrystalline Cellulose	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

Primary Outcome Measures

Name	Time	Method
Pilot Trial - Feasibility	90 days	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?

Trial Locations

Locations (14)

St. John's Mercy Medical Center; 🇺🇸 Saint Louis, Missouri, United States

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada

Vancouver General Hospital; 🇨🇦 Vancouver, British Columbia, Canada

St. Paul's Hospital; 🇨🇦 Vancouver, British Columbia, Canada

Vancouver Island Health Authority; 🇨🇦 Victoria, British Columbia, Canada

St Michael's Hospital; 🇨🇦 Toronto, Ontario, Canada

Hopital de l'Enfant Jesus; 🇨🇦 Quebec City, Quebec, Canada

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Hamilton Health Science - Juravinski Hospital; 🇨🇦 Hamilton, Ontario, Canada

St Joseph's Healthcare Hamilton; 🇨🇦 Hamilton, Ontario, Canada

Hamilton Health Science - Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada

Ottawa Hospital Research Institute - Civic Campus; 🇨🇦 Ottawa, Ontario, Canada

Ottawa Research Institute - General Hospital; 🇨🇦 Ottawa, Ontario, Canada

University Health Network - Toronto Western Hospital; 🇨🇦 Toronto, Ontario, Canada