Prevention of Nosocomial Infections in Critically Ill Patients With Lactoferrin: A Randomized, Double-Blind, Placebo-Controlled Study

Muscedere, John; Maslove, David; Boyd, J. Gordon; O'Callaghan, Nicole; Sibley, Stephanie; Reynolds, Steven; Albert, Martin; Hall, Richard; Jiang, Xuran; Day, Andrew G.; Jones, Gwyneth E.; Lamontagne, François

doi:10.1097/ccm.0000000000003294

Cited by 19 publications

(29 citation statements)

References 33 publications

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“…We re-analyzed Gene Expression Omnibus dataset (GSE118657) to illustrate the methodology. [6] The dataset is a Phase II randomized controlled trial assessing the effect of lactoferrin on critically ill patients undergoing mechanical ventilation (a total of 61 patients, 32 patients in the lactoferrin group, and the remaining, the placebo group). Gene expressions with a total of 49,495 genes were measured at the first day of admission for each patient.…”

Section: Methodsmentioning

confidence: 99%

A test for treatment effects in randomized controlled trials, harnessing the power of ultrahigh dimensional big data

Lee

Lin²

2019

Medicine

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Section: Methodsmentioning

confidence: 99%

A test for treatment effects in randomized controlled trials, harnessing the power of ultrahigh dimensional big data

Lee

Lin²

2019

Medicine

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“…A secondary analysis of the PREVAIL study, a phase 2 randomized, multi-centre, double-blinded placebo controlled trial conducted in five Canadian tertiary ICUs studying the effect of lactoferrin on the acquisition of NIs [32]. The protocol for this study has been published and the trial was registered at www.clinicaltrials.gov on 18 November 2013 (registration number NCT01996579) [33].…”

Section: Designmentioning

confidence: 99%

The relationship between immune status as measured by stimulated ex-vivo tumour necrosis factor alpha levels and the acquisition of nosocomial infections in critically ill mechanically ventilated patients

Levin

Boyd

Day

et al. 2020

ICMx

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Introduction Immunological dysfunction is common in critically ill patients but its clinical significance and the optimal method to measure it are unknown. The level of tumor necrosis factor alpha (TNF-α) after ex-vivo whole blood stimulation with lipopolysaccharide (LPS) has been proposed as a possible method to quantify immunological function. We hypothesized that in a cohort of critically ill patients, those with a lower post-stimulation TNF-α level would have increased rates of nosocomial infections (NIs) and worse clinical outcomes. Methods A secondary analysis of a phase 2 randomized, multi-centre, double-blinded placebo-controlled trial. As there was no difference between treatment and control arms in outcomes and NI rate, all the patients were analyzed as one cohort. On enrolment, day 4, 7, and weekly until day 28, whole blood was incubated with LPS ex-vivo and subsequent TNF-α level was measured. Patients were grouped in tertiles according to delta and peak TNF-α level. The primary outcome was the association between NIs and tertiles of TNF-α level post LPS stimulation; secondary outcomes included ICU and 90-day mortality, and ICU and hospital length of stay. Results Data was available for 201 patients. Neither the post LPS stimulation delta TNF-α group nor the peak TNF-α post-stimulation group were associated with the development of NIs or clinical outcomes. Patients in the highest tertile for post LPS stimulation delta TNF-α compared to the lowest tertile were younger [61.1 years ± 15.7 vs. 68.6 years ± 12.8 standard deviations (SD) in the lowest tertile], had lower acuity of illness (APACHE II 25.0 ± 9.7 vs. 26.7 ± 6.1) and had lower baseline TNF-α (9.9 pg/mL ± 19.0 vs. 31.0 pg/mL ± 68.5). When grouped according to peak post-stimulation TNF-α levels, patients in the highest tertile had higher serum TNF-α at baseline (21.3 pg/mL ± 66.7 compared to 6.5 pg/mL ± 9.0 in the lowest tertile). Conclusion In this prospective multicenter study, ex-vivo stimulated TNF-α level was not associated with the occurrence of NIs or clinical outcomes. Further study is required to better ascertain whether TNF levels and ex-vivo stimulation can be used to characterize immune function in critical illness and if other assays might be better suited to this task.

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“…Nosocomial infection remains a major source of morbidity in patients admitted to the ICU. Oral supplementation with the iron-binding glycoprotein, lactoferrin, appears to reduce nosocomial infection in preterm infants, although the results of large studies are awaited; results have not been replicated in the adult ICU setting [44, 45].…”

Section: Iron Metabolism and Critical Illnessmentioning

confidence: 99%

Iron Metabolism: An Emerging Therapeutic Target in Critical Illness

Litton

Lim

2019

Crit Care

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This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2019. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2019 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

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Prevention of Nosocomial Infections in Critically Ill Patients With Lactoferrin: A Randomized, Double-Blind, Placebo-Controlled Study

Abstract: Lactoferrin did not improve the primary outcome of antibiotic-free days, nor any of the secondary outcomes. Our data do not support the conduct of a larger phase 3 trial.

Cited by 19 publications

References 33 publications

A test for treatment effects in randomized controlled trials, harnessing the power of ultrahigh dimensional big data

A test for treatment effects in randomized controlled trials, harnessing the power of ultrahigh dimensional big data

The relationship between immune status as measured by stimulated ex-vivo tumour necrosis factor alpha levels and the acquisition of nosocomial infections in critically ill mechanically ventilated patients

Iron Metabolism: An Emerging Therapeutic Target in Critical Illness

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