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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01782755
Recruitment Status : Completed
First Posted : February 4, 2013
Last Update Posted : August 28, 2019
Canadian Institutes of Health Research (CIHR)
Technology Evaluation in the Elderly Network (TVN)
Physician's Services Incorporated (PSI)
Hamilton Academy of Health Science Research Organization (HAHSO)
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
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 Drug: L. rhamnosus GG - Probiotic Other: Placebo - Microcrystalline Cellulose Phase 2

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: NCT01782755

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT): A Feasibility Clinical Trial
Study Start Date : October 2013
Actual Primary Completion Date : August 2014
Actual Study Completion Date : January 2015

Arm Intervention/treatment
Active Comparator: Lactobacillus rhamnosus GG
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
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
Other Name: Culturelle Probiotic

Placebo Comparator: Placebo
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
Placebo capsule, twice daily (containing Microcrystalline Cellulose)
Other Name: Placebo

Primary Outcome Measures :
  1. Pilot Trial - Feasibility [ Time Frame: 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?

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

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

Exclusion criteria:

  1. Mechanical ventilation exceeding 72 hours at time of screening.
  2. 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).
  3. 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).
  4. 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.
  5. Strict contraindication or inability to receive enteral medications.
  6. Pregnancy.
  7. Intent to withdraw advanced life support.
  8. Enrolment in this or an ongoing related trial.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01782755

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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
St. John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
Canada, British Columbia
Vancouver General Hospital
Vancouver, British Columbia, Canada, V5Z 1M9
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z1Y6
Vancouver Island Health Authority
Victoria, British Columbia, Canada, V8R 1J8
Canada, Ontario
Hamilton Health Science - Hamilton General Hospital
Hamilton, Ontario, Canada, L8L 2X2
St Joseph's Healthcare Hamilton
Hamilton, Ontario, Canada, L8N 4A6
Hamilton Health Science - Juravinski Hospital
Hamilton, Ontario, Canada, L8V 1C3
Ottawa Hospital Research Institute - Civic Campus
Ottawa, Ontario, Canada, K1H 8G7
Ottawa Research Institute - General Hospital
Ottawa, Ontario, Canada, K1H 8L6
St Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
University Health Network - Toronto Western Hospital
Toronto, Ontario, Canada
Canada, Quebec
Hopital de l'Enfant Jesus
Quebec City, Quebec, Canada, G1J 1Z4
Sponsors and Collaborators
McMaster University
Canadian Institutes of Health Research (CIHR)
Technology Evaluation in the Elderly Network (TVN)
Physician's Services Incorporated (PSI)
Hamilton Academy of Health Science Research Organization (HAHSO)
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Principal Investigator: Deborah J Cook, MD McMaster University
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):

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Responsible Party: McMaster University Identifier: NCT01782755    
Other Study ID Numbers: 28012013
First Posted: February 4, 2013    Key Record Dates
Last Update Posted: August 28, 2019
Last Verified: March 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by McMaster University:
Ventilator Associated Pneumonia (VAP)
Antibiotic-Associated Diarrhea
Additional relevant MeSH terms:
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Pneumonia, Ventilator-Associated
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Signs and Symptoms, Digestive
Cross Infection