Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial—PROSPECT: protocol for a feasibility randomized pilot trial

Johnstone, Jennie; Meade, Maureen O.; Marshall, John C.; Heyland, Daren K.; Surette, Michael G.; Bowdish, Dawn M. E.; Lauzier, François; Thebane, Lehana; Cook, Deborah J.

doi:10.1186/s40814-015-0013-3

Cited by 18 publications

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References 42 publications

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“…Randomization was stratified by ICU and by medical, surgical, or trauma status, in variable unspecified block sizes. Further details are reported in the protocol manuscript [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

“…Using each patient as the unit of analysis, rather than doses prescribed, the PROSPECT pilot trial sample size calculation would have claimed feasibility if at least 80 % of the patients achieved successful protocol adherence. Assuming a preliminary estimate of 0.85, and a margin of error of 0.05, recruiting 150 patients will give a 95 % confidence interval estimate of the proportion of patients with successful protocol adherence with a lower bound of 0.80 [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

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Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial—PROSPECT: a pilot trial

Cook

Johnstone

Marshall

et al. 2016

Trials

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BackgroundProbiotics are live microorganisms that may confer health benefits when ingested. Randomized trials suggest that probiotics significantly decrease the incidence of ventilator-associated pneumonia (VAP) and the overall incidence of infection in critically ill patients. However, these studies are small, largely single-center, and at risk of bias. The aim of the PROSPECT pilot trial was to determine the feasibility of conducting a larger trial of probiotics to prevent VAP in mechanically ventilated patients in the intensive care unit (ICU).MethodsIn a randomized blinded trial, patients expected to be mechanically ventilated for ≥72 hours were allocated to receive either 1 × 1010 colony-forming units of Lactobacillus rhamnosus GG or placebo, twice daily. Patients were excluded if they were at increased risk of L. rhamnosus GG infection or had contraindications to enteral medication. Feasibility objectives were: (1) timely recruitment; (2) maximal protocol adherence; (3) minimal contamination; and (4) estimated VAP rate ≥10 %. We also measured other infections, diarrhea, ICU and hospital length of stay, and mortality.ResultsOverall, in 14 centers in Canada and the USA, all feasibility goals were met: (1) 150 patients were randomized in 1 year; (2) protocol adherence was 97 %; (3) no patients received open-label probiotics; and (4) the VAP rate was 19 %. Other infections included: bloodstream infection (19.3 %), urinary tract infections (12.7 %), and skin and soft tissue infections (4.0 %). Diarrhea, defined as Bristol type 6 or 7 stools, occurred in 133 (88.7 %) of patients, the median length of stay in ICU was 12 days (quartile 1 to quartile 3, 7–18 days), and in hospital was 26 days (quartile 1 to quartile 3, 14–44 days); 23 patients (15.3 %) died in the ICU.ConclusionsThe PROSPECT pilot trial supports the feasibility of a larger trial to investigate the effect of L. rhamnosus GG on VAP and other nosocomial infections in critically ill patients.Trial registrationClinicaltrials.gov NCT01782755. Registered on 29 January 2013.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1495-x) contains supplementary material, which is available to authorized users.

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“…Randomization was stratified by ICU and by medical, surgical, or trauma status, in variable unspecified block sizes. Further details are reported in the protocol manuscript [ 12 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial—PROSPECT: a pilot trial

Cook

Johnstone

Marshall

et al. 2016

Trials

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“…NCT01782755), assessing the incremental cost-effectiveness ratio (ICER) of probiotics versus usual care for critically ill adult patients. [18][19][20] MEthods overview of prospect PROSPECT is a randomised, double-blinded multicentre controlled trial. It used a central system for concealed 1:1 ratio to randomise patients (in variable unspecified block sizes, stratified by centre and by medical, surgical or trauma admission status) to either 1×10 10 colony-forming units of Lactobacillus rhamnosus GG (iHealth, Inc.) or an identical placebo suspended in tap water administered twice daily via feeding tube in the ICU.…”

Section: Current Knowledgementioning

confidence: 99%

“…Sample size calculation has been previously described. [18][19][20] E-ProsPECt design The primary objective of E-PROSPECT is to estimate the incremental cost per VAP prevented arising from a prevention strategy of using probiotics with usual care (the probiotics arm) versus usual care without probiotics (the usual care arm) during hospitalisation. Our secondary analyses of ICERs include healthcare-associated complications (CDAD, AAD) and mortality.…”

Section: Current Knowledgementioning

confidence: 99%

“…Our secondary analyses of ICERs include healthcare-associated complications (CDAD, AAD) and mortality. [18][19][20] Our economic evaluation will be performed from the public healthcare payer's perspective, 21 over the time horizon of the ICU admission to hospital discharge or death (table 1). Our economic evaluation protocol was developed (table 1) according to established CHEERS (Consolidated Health Economic Evaluation Reporting Standards) and international cost-effectiveness analysis guidelines.…”

Section: Current Knowledgementioning

confidence: 99%

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Economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): study protocol

et al. 2020

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IntroductionVentilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysisThe objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and disseminationStudy approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration numberNCT01782755; Pre-results.

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Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients

Johnstone¹,

Meade²,

Lauzier³

et al. 2021

JAMA

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for the Prevention of Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT) Investigators and the Canadian Critical Care Trials Group IMPORTANCE Growing interest in microbial dysbiosis during critical illness has raised questions about the therapeutic potential of microbiome modification with probiotics. Prior randomized trials in this population suggest that probiotics reduce infection, particularly ventilator-associated pneumonia (VAP), although probiotic-associated infections have also been reported.OBJECTIVE To evaluate the effect of Lactobacillus rhamnosus GG on preventing VAP, additional infections, and other clinically important outcomes in the intensive care unit (ICU). DESIGN, SETTING, AND PARTICIPANTS Randomized placebo-controlled trial in 44 ICUs in Canada, the United States, and Saudi Arabia enrolling adults predicted to require mechanical ventilation for at least 72 hours. A total of 2653 patients were enrolled from October 2013 to March 2019 (final follow-up, October 2020). INTERVENTIONS Enteral L rhamnosus GG (1 × 10 10 colony-forming units) (n = 1321) or placebo (n = 1332) twice daily in the ICU. MAIN OUTCOMES AND MEASURES The primary outcome was VAP determined by duplicate blinded central adjudication. Secondary outcomes were other ICU-acquired infections including Clostridioides difficile infection, diarrhea, antimicrobial use, ICU and hospital length of stay, and mortality. RESULTS Among 2653 randomized patients (mean age, 59.8 years [SD], 16.5 years), 2650 (99.9%) completed the trial (mean age, 59.8 years [SD], 16.5 years; 1063 women [40.1%.]with a mean Acute Physiology and Chronic Health Evaluation II score of 22.0 (SD, 7.8) and received the study product for a median of 9 days (IQR, 5-15 days). VAP developed among 289 of 1318 patients (21.9%) receiving probiotics vs 284 of 1332 controls (21.3%; hazard ratio [HR], 1.03 (95% CI, 0.87-1.22; P = .73, absolute difference, 0.6%, 95% CI, -2.5% to 3.7%). None of the 20 prespecified secondary outcomes, including other ICU-acquired infections, diarrhea, antimicrobial use, mortality, or length of stay showed a significant difference. Fifteen patients (1.1%) receiving probiotics vs 1 (0.1%) in the control group experienced the adverse event of L rhamnosus in a sterile site or the sole or predominant organism in a nonsterile site (odds ratio, 14.02; 95% CI, 1.79-109.58; P < .001).CONCLUSIONS AND RELEVANCE Among critically ill patients requiring mechanical ventilation, administration of the probiotic L rhamnosus GG compared with placebo, resulted in no significant difference in the development of ventilator-associated pneumonia. These findings do not support the use of L rhamnosus GG in critically ill patients.

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Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial—PROSPECT: protocol for a feasibility randomized pilot trial

Cited by 18 publications

References 42 publications

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial—PROSPECT: a pilot trial

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial—PROSPECT: a pilot trial

Economic evaluation alongside the Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (E-PROSPECT): study protocol

Effect of Probiotics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients

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