Evidence map›Paper›PMID 41013603›Full record

Trial reportTrials2025

Coenrollment of critically ill patients in PROSPECT: characteristics and association with treatment efficacy and safety.

Alex Thabane, Diane Heels-Ansdell, Nicole Zytaruk, Jennie Johnstone, François Lauzier, Yaseen M Arabi, John Muscedere, France Clarke, Lori Hand, Irene Watpool and 15 more

Registry-linked trialAbstract readRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Trials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02462590 (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial), which is not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02462590 phase4completednot on this map

Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial (PROSPECT)

TypeinterventionalSponsorMcMaster UniversityRan2015 to 2020Enrolled2,650ConditionsVentilator Associated Pneumonia, Infections, C-Difficile, Antibiotic-associated DiarrheaArmsL. rhamnosus GG - Probiotic, Placebo - Microcrystalline Cellulose
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

25 authors.

Alex ThabaneDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.ORCID http://orcid.org/0000-0002-1516-9584
Diane Heels-AnsdellDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Nicole ZytarukDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Jennie JohnstoneDepartment of Medicine, University of Toronto, Toronto, Canada.
François LauzierDepartment of Medicine, Université Laval, Québec City, Canada.
Yaseen M ArabiKing Saud Bin Abdulaziz University for Health Sciences and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
John MuscedereDepartment of Critical Care Medicine, Queen's University, Kingston, Canada.
France ClarkeDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Lori HandDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Irene WatpoolDepartment of Critical Care Medicine, University of Ottawa, Ottawa, Canada.
Rebecca PorteousDepartment of Critical Care Medicine, University of Ottawa, Ottawa, Canada.
Gyan SanduInterdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
Marlene SantosInterdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
Danae TassyHôpital Maisonneuve-Rosemont, Montréal, Canada.
John MarshallInterdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
Lauralyn McIntyreDepartment of Critical Care Medicine, University of Ottawa, Ottawa, Canada.
Ian BallDepartment of Critical Care Medicine, Western University, London, Canada.
Bram RochwergDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.
Tim KarachiDepartment of Medicine, McMaster University Medical Center, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada.
Ryan ZarychanskiDepartment of Critical Care Medicine, University of Manitoba, Winnipeg, Canada.
Francois MarquisHôpital Maisonneuve-Rosemont, Montréal, Canada.
Jan O FriedrichInterdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, Canada.
Paul LyseckiDepartment of Critical Care Medicine, Joseph Brant Hospital, Burlington, Canada.
Deborah CookDepartment of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada. debcook@mcmaster.ca.
PROSPECT Investigators and the Canadian Critical Care Trials Group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionCoenrollment is the enrollment of one participant into more than one study. While coenrollment can enhance research efficiency, it theoretically may result in treatment interactions that distort effect estimates. This study aimed to explore the sensitivity of safety and efficacy outcomes to coenrollment in an international, blinded randomized controlled trial evaluating probiotic use in critically ill patients (PROSPECT: Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial; [NCT02462590]).

methodsIn this planned secondary analysis of PROSPECT, we performed Cox proportional hazards analyses to assess the sensitivity of the treatment effect of probiotics to coenrollment on the primary outcome of ventilator-associated pneumonia. Secondarily, we examined the characteristics of coenrolled patients, studies, and centers using descriptive statistics, explored factors associated with coenrollment via a multilevel logistic regression model, and conducted Fisher's exact tests to evaluate the difference in adverse event rates (defined as Lactobacillus species from a sterile site or cultured as the sole or predominant organism from a nonsterile site) by coenrollment status.

resultsOf 2650 PROSPECT participants recruited across 44 centers, 568 patients (21.4%) were coenrolled a total of 680 times across 115 studies. Coenrollment did not modify the effect of probiotics on the primary outcome of ventilator-associated pneumonia (p = 0.630). Patients who were coenrolled in any other study had a higher rate of adverse events compared to non-coenrolled patients (p = 0.011); however, post hoc testing found no difference in adverse events between patients coenrolled specifically into at least one other randomized controlled trial and patients who were not coenrolled into another randomized controlled trial (i.e., coenrolled into an observational study or not coenrolled at all; p = 0.126). Multivariable analyses found more severely ill patients (p = 0.038) and patients from centers with a longer PROSPECT recruitment period (p = 0.047) were more likely to be coenrolled.

conclusionIn this international, blinded trial, one-fifth of patients enrolled were coenrolled in at least one other study, which had no influence on the effect of probiotics on the primary outcome. Coenrolled patients were more likely to have higher disease severity, and to be recruited from a center with a longer history of participation in PROSPECT.

trial registrationThe PROSPECT trial was registered in ClinicalTrials.gov NCT02462590. Registered on June 2015.

Indexed as

Patient SelectionPneumonia, Ventilator-AssociatedProbioticsAgedCritical IllnessFemaleHumansMaleMiddle AgedProportional Hazards ModelsRisk FactorsTime FactorsTreatment OutcomeCoenrollmentCritical careProbioticsPROSPECTRandomized trial

Identifiers

PMID41013603
PMCPMC12465574

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.