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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by McMaster University
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Technology Evaluation for the Elderly (TVN)
Physician's Services Incorporated (PSI)
Hamilton Academy of Health Science Research Organization (HAHSO)
Information provided by (Responsible Party):
McMaster University
ClinicalTrials.gov Identifier:
NCT01782755
First received: January 29, 2013
Last updated: May 29, 2015
Last verified: May 2015
  Purpose

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 Intervention 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
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT): A Feasibility Clinical Trial

Resource links provided by NLM:


Further study details as provided by McMaster University:

Primary Outcome Measures:
  • Pilot Trial - Feasibility [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    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?


Estimated Enrollment: 250
Study Start Date: October 2013
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01782755

Contacts
Contact: Deborah J Cook, MD 905-522-1155 ext 35325 debcook@mcmaster.ca
Contact: Nicole L Zytaruk, Reg. N 905-522-1155 ext 35325 zytaruk@mcmaster.ca

Locations
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Rodrigo Carten-Ceba, MD    507-255-1829    CartinCeba.Rodrigo@mayo.edu   
Contact: Laurie Meade, RN    507-255-1829    Meade.Laurie@mayo.edu   
Principal Investigator: Rodrigo Carten-Ceba, MD         
United States, Missouri
St. John's Mercy Medical Center Recruiting
St. Louis, Missouri, United States, 63141
Contact: Robert Taylor, MD    314-251-6933 ext 20139    Robert.Taylor2@Mercy.Net   
Contact: Jackie O'Brien, RN    314-251-6933 ext 20139    Jacklyn.O'Brien@Mercy.Net   
Principal Investigator: Robert Taylor, MD         
Canada, British Columbia
St. Paul's Hospital Recruiting
Vancouver, British Columbia, Canada, V6Z1Y6
Contact: Peter Dodek, MD    604-806-9023    pedodek@interchange.ubc.ca   
Contact: Betty-Jean Ashley       bjashley@mail.cheos.ubc.ca   
Principal Investigator: Peter Dodek, MD         
Vancouver General Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: William Henderson, MD    604-875-5949    william.henderson@vch.ca   
Contact: Denise Foster, RN    604-875-4111 ext 68336    Denise.Foster@vch.ca   
Principal Investigator: William Henderson, MD         
Vancouver Island Health Authority Recruiting
Victoria, British Columbia, Canada, V8R 1J8
Contact: Gordon Wood, MD    1-250-370-8111 ext 12847    Gordon.Wood@viha.ca   
Contact: Jennifer Good, RN    1-250-370-8111 ext 12847    Jennifer.Good@viha.ca   
Principal Investigator: Gordon Wood, MD         
Canada, Ontario
Hamilton Health Science - Juravinski Hospital Recruiting
Hamilton, Ontario, Canada, L8V 1C3
Contact: Tim Kirachi, MD    905-521-2100 ext 75180    karachi@univmail.cis.mcmaster.ca   
Contact: Ellen McDonald, RN    905-522-1155 ext 35092    emcdonal@mcmaster.ca   
Principal Investigator: Tim Kirachi, MD         
St Joseph's Healthcare Hamilton Recruiting
Hamilton, Ontario, Canada, L8N 4A6
Contact: Deborah Cook, MD    905-522-1155 ext 35325    debcook@mcmaster.ca   
Contact: Nicole Zytaruk, Reg. N    905-522-1155 ext 35325    zytaruk@mcmaster.ca   
Principal Investigator: Deborah Cook, MD         
Hamilton Health Science - Hamilton General Hospital Recruiting
Hamilton, Ontario, Canada, L8L 2X2
Contact: Maureen Meade, MD    905-527-7077    meadema@HHSC.ca   
Contact: Lori Hand, RRT    905-972-1294    handlori@hhsc.ca   
Principal Investigator: Maureen Meade, MD         
Ottawa Research Institute - General Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Laurlyn McIntyre, MD    613-737-8899 ext 73231    lmcintyre@ottawahospital.on.ca   
Contact: Irene Watpool, RN    613-737-8724    iwatpool@ottawahospital.on.ca   
Principal Investigator: Lauralyn McIntyre, MD         
Ottawa Hospital Research Institute - Civic Campus Recruiting
Ottawa, Ontario, Canada, K1H 8G7
Contact: Lauralyn McIntyre, MD    613-737-8899 ext 73231    lmcintyre@ottawahospital.on.ca   
Contact: Tracy McArdle, RN    613-798-5555 ext 17076    tmcardle@ottawahospital.on.ca   
Principal Investigator: Lauralyn McIntyre, MD         
Mount Sinai Hospital Recruiting
Toronto, Ontario, Canada, M5G 1X5
Contact: Sangeeta Mehta, MD    416-586-4679    samehta@mtsinai.on.ca   
Contact: Brittany Giacomino, RN    416-586-4800 ext 2549    BGiacomino@mtsinai.on.ca   
Principal Investigator: Sangeeta Mehta, MD         
St Michael's Hospital Recruiting
Toronto, Ontario, Canada, M5B 1W8
Contact: John Marshall, MD    416-864-6060 ext 3538    marshallj@smh.toronto.on.ca   
Contact: Orla Smith, Reg. N    416-864-6060 ext 3179    smitho@smh.toronto.on.ca   
Principal Investigator: John Marshall, MD         
University Health Network - Toronto Western Hospital Recruiting
Toronto, Ontario, Canada
Contact: Margaret Herridge, MD    416-340-4800 ext 3057    dr.margaret.herridge@uhn.ca   
Contact: Andrea Matte, RRT    416-340-4800    Andrea.Matte@uhn.on.ca   
Principal Investigator: Margaret Herridge, MD         
Canada, Quebec
Hopital de l'Enfant Jesus Recruiting
Quebec City, Quebec, Canada, G1J 1Z4
Contact: Francois Lauzier, MD    418-649-0252    francois.lauzier@med.ulaval.ca   
Contact: Sara-Judith Breton, RN    418-649-0252    sarah-judith.breton.cha@ssss.gouv.qc.ca   
Principal Investigator: Francois Lauzier, MD         
Sponsors and Collaborators
McMaster University
Canadian Institutes of Health Research (CIHR)
Technology Evaluation for the Elderly (TVN)
Physician's Services Incorporated (PSI)
Hamilton Academy of Health Science Research Organization (HAHSO)
Investigators
Principal Investigator: Deborah J Cook, MD McMaster University
  More Information

Additional Information:
No publications provided

Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT01782755     History of Changes
Other Study ID Numbers: 28012013
Study First Received: January 29, 2013
Last Updated: May 29, 2015
Health Authority: Canada: Health Canada
Canada: Ethics Review Committee

Keywords provided by McMaster University:
Probiotics
Ventilator Associated Pneumonia (VAP)
Infection
Antibiotic-Associated Diarrhea
C-Difficile

Additional relevant MeSH terms:
Diarrhea
Pneumonia
Pneumonia, Ventilator-Associated
Cross Infection
Infection
Lung Diseases
Lung Injury
Respiratory Tract Diseases
Respiratory Tract Infections
Signs and Symptoms
Signs and Symptoms, Digestive
Ventilator-Induced Lung Injury

ClinicalTrials.gov processed this record on July 01, 2015