Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT): A Feasibility Clinical Trial
| Status: | Completed |
|---|---|
| Conditions: | Pneumonia, Pneumonia, Gastrointestinal |
| Therapuetic Areas: | Gastroenterology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/17/2018 |
| Start Date: | October 2013 |
| End Date: | January 2015 |
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.
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.
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
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
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.
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