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

Antibiotic-Associated Diarrhea Clinical Trial

— PROSPECT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01782755
• Other study ID #: 28012013
• Status: Completed
• Phase: Phase 2
• Start date: October 2013
• Est. completion date: January 2015

Study information

• Verified date: March 2016
• Source: McMaster University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: January 2015
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

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:
• Placebo - Microcrystalline Cellulose
Placebo capsule, twice daily (containing Microcrystalline Cellulose)

Locations

Country	Name	City	State
Canada	Hamilton Health Science - Hamilton General Hospital	Hamilton	Ontario
Canada	Hamilton Health Science - Juravinski Hospital	Hamilton	Ontario
Canada	St Joseph's Healthcare Hamilton	Hamilton	Ontario
Canada	Ottawa Hospital Research Institute - Civic Campus	Ottawa	Ontario
Canada	Ottawa Research Institute - General Hospital	Ottawa	Ontario
Canada	Hopital de l'Enfant Jesus	Quebec City	Quebec
Canada	Mount Sinai Hospital	Toronto	Ontario
Canada	St Michael's Hospital	Toronto	Ontario
Canada	University Health Network - Toronto Western Hospital	Toronto	Ontario
Canada	St. Paul's Hospital	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia
Canada	Vancouver Island Health Authority	Victoria	British Columbia
United States	Mayo Clinic	Rochester	Minnesota
United States	St. John's Mercy Medical Center	Saint Louis	Missouri

Sponsors (5)

Lead Sponsor	Collaborator
McMaster University	Canadian Institutes of Health Research (CIHR), Hamilton Academy of Health Science Research Organization (HAHSO), Physician's Services Incorporated (PSI), Technology Evaluation in the Elderly Network (TVN)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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

External Links

•   PROSPECT Trial