Prevention of nosocomial infections in critically ill patients with lactoferrin: A randomized, double-blind, placebo-controlled study

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

doi:10.1097/CCM.0000000000003294

Prevention of nosocomial infections in critically ill patients with lactoferrin: A randomized, double-blind, placebo-controlled study

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

Medicine

Medicine

Research output: Contribution to journal › Article › peer-review

16 Citations (Scopus)

Abstract

Objective: To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study. Design: Phase 2, multicenter, randomized, double-blind, placebocontrolled study. Setting: Medical-surgical ICUs. Patients: Adult, critically ill patients receiving invasive mechanical ventilation. Interventions: Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days. Measurements and Main Results: Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [sd], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; p = 0.91) and nosocomial infections (0.3 [0.7] vs 0.4 [0.6] per patient; p = 0.48) did not differ between lactoferrin and placebo groups, respectively. Clinical outcomes for lactoferrin versus placebo were as follows: ICU length of stay (14.5 [18.0] vs 15.0 [37.3] d; p = 0.82), hospital length of stay (25.0 [25.9] vs 28.1 [44.6] d; p = 0.57), hospital mortality (41.1% vs 30.5%; p = 0.11), and 90-day mortality (44.9% vs 32.4%; p = 0.06). Biomarker levels did not differ between the groups. Conclusions: 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.

Original language	English
Pages (from-to)	1450-1456
Number of pages	7
Journal	Critical Care Medicine
Volume	46
Issue number	9
DOIs	https://doi.org/10.1097/CCM.0000000000003294
Publication status	Published - 2018

Bibliographical note

Funding Information:
1Department of Critical Care Medicine, Queen’s University, Kingston, ON, Canada. 2Department of Medicine, University of British Columbia, Vancouver, BC, Canada. 3Department of Biophysiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada. 4Centre de Recherche de l’Hôpital du Sacré-Coeur de Montréal, Critical Care and Medicine Departments, Université de Montréal, Montréal, QC, Canada. 5Department of Critical Care Medicine, Dalhousie University and the Nova Scotia Health Authority, Halifax, NS, Canada. 6Kingston General Hospital, Kingston, ON, Canada. 7Department of Critical Care Medicine, University of Ottawa, Ottawa, ON, Canada. 8Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada. The study was conceptualized by Dr. Muscedere. All authors contributed to the conduct of the study and/or provided input on the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grants from the Lotte and John Hecht Memorial Foundation and South Eastern Academic Medical Association. The bovine lactoferrin was provided by Advanced Orthomolecular Research. The funders did not have any role in the conceptualization, conduct of the study, study analysis, interpretation of the data, or writing of the article. Dr. Muscedere, Dr. Maslove, Dr. Boyd, Ms. O’Callaghan, Dr. Reynolds, Dr. Hall, and Dr. Jones disclosed off-label product use of lactoferrin for the reduction of nosocomial infections. Dr. Boyd’s institution received funding from South Eastern Academic Medical Association (SEAMO) Innovation Fund and SEAMO New Clinician Scientist Award, and he received funding from Physician Services Incorporated New Clinician Science Award. Dr. Hall’s institution received funding from Queen’s University, Canadian Institutes for Health Research, and GlaxoSmithKline. Mr. Day’s institution received funding from Queen’s University Faculty of Health Sciences to

Publisher Copyright:
Copyright © 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

ASJC Scopus Subject Areas

Critical Care and Intensive Care Medicine

Access to Document

10.1097/CCM.0000000000003294

Cite this

Muscedere, J., Maslove, D. M., Boyd, J. G., O'Callaghan, N., Sibley, S., Reynolds, S., Albert, M., Hall, R., Jiang, X., Day, A. G., Jones, G., & Lamontagne, F. (2018). Prevention of nosocomial infections in critically ill patients with lactoferrin: A randomized, double-blind, placebo-controlled study. Critical Care Medicine, 46(9), 1450-1456. https://doi.org/10.1097/CCM.0000000000003294

Muscedere, J, Maslove, DM, Boyd, JG, O'Callaghan, N, Sibley, S, Reynolds, S, Albert, M, Hall, R, Jiang, X, Day, AG, Jones, G & Lamontagne, F 2018, 'Prevention of nosocomial infections in critically ill patients with lactoferrin: A randomized, double-blind, placebo-controlled study', Critical Care Medicine, vol. 46, no. 9, pp. 1450-1456. https://doi.org/10.1097/CCM.0000000000003294

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title = "Prevention of nosocomial infections in critically ill patients with lactoferrin: A randomized, double-blind, placebo-controlled study",

abstract = "Objective: To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study. Design: Phase 2, multicenter, randomized, double-blind, placebocontrolled study. Setting: Medical-surgical ICUs. Patients: Adult, critically ill patients receiving invasive mechanical ventilation. Interventions: Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days. Measurements and Main Results: Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [sd], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; p = 0.91) and nosocomial infections (0.3 [0.7] vs 0.4 [0.6] per patient; p = 0.48) did not differ between lactoferrin and placebo groups, respectively. Clinical outcomes for lactoferrin versus placebo were as follows: ICU length of stay (14.5 [18.0] vs 15.0 [37.3] d; p = 0.82), hospital length of stay (25.0 [25.9] vs 28.1 [44.6] d; p = 0.57), hospital mortality (41.1% vs 30.5%; p = 0.11), and 90-day mortality (44.9% vs 32.4%; p = 0.06). Biomarker levels did not differ between the groups. Conclusions: 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.",

author = "John Muscedere and Maslove, {David M.} and Boyd, {J. Gordon} and Nicole O'Callaghan and Stephanie Sibley and Steven Reynolds and Martin Albert and Richard Hall and Xuran Jiang and Day, {Andrew G.} and Gwyneth Jones and Francois Lamontagne",

note = "Funding Information: 1Department of Critical Care Medicine, Queen{\textquoteright}s University, Kingston, ON, Canada. 2Department of Medicine, University of British Columbia, Vancouver, BC, Canada. 3Department of Biophysiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada. 4Centre de Recherche de l{\textquoteright}H{\^o}pital du Sacr{\'e}-Coeur de Montr{\'e}al, Critical Care and Medicine Departments, Universit{\'e} de Montr{\'e}al, Montr{\'e}al, QC, Canada. 5Department of Critical Care Medicine, Dalhousie University and the Nova Scotia Health Authority, Halifax, NS, Canada. 6Kingston General Hospital, Kingston, ON, Canada. 7Department of Critical Care Medicine, University of Ottawa, Ottawa, ON, Canada. 8Department of Medicine, Universit{\'e} de Sherbrooke, Sherbrooke, QC, Canada. The study was conceptualized by Dr. Muscedere. All authors contributed to the conduct of the study and/or provided input on the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal{\textquoteright}s website (http://journals.lww.com/ccmjournal). Supported, in part, by grants from the Lotte and John Hecht Memorial Foundation and South Eastern Academic Medical Association. The bovine lactoferrin was provided by Advanced Orthomolecular Research. The funders did not have any role in the conceptualization, conduct of the study, study analysis, interpretation of the data, or writing of the article. Dr. Muscedere, Dr. Maslove, Dr. Boyd, Ms. O{\textquoteright}Callaghan, Dr. Reynolds, Dr. Hall, and Dr. Jones disclosed off-label product use of lactoferrin for the reduction of nosocomial infections. Dr. Boyd{\textquoteright}s institution received funding from South Eastern Academic Medical Association (SEAMO) Innovation Fund and SEAMO New Clinician Scientist Award, and he received funding from Physician Services Incorporated New Clinician Science Award. Dr. Hall{\textquoteright}s institution received funding from Queen{\textquoteright}s University, Canadian Institutes for Health Research, and GlaxoSmithKline. Mr. Day{\textquoteright}s institution received funding from Queen{\textquoteright}s University Faculty of Health Sciences to Publisher Copyright: Copyright {\textcopyright} 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.",

year = "2018",

doi = "10.1097/CCM.0000000000003294",

language = "English",

volume = "46",

pages = "1450--1456",

journal = "Critical Care Medicine",

issn = "0090-3493",

publisher = "Lippincott Williams and Wilkins",

number = "9",

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TY - JOUR

T1 - Prevention of nosocomial infections in critically ill patients with lactoferrin

T2 - A randomized, double-blind, placebo-controlled study

AU - Muscedere, John

AU - Maslove, David M.

AU - Boyd, J. Gordon

AU - O'Callaghan, Nicole

AU - Sibley, Stephanie

AU - Reynolds, Steven

AU - Albert, Martin

AU - Hall, Richard

AU - Jiang, Xuran

AU - Day, Andrew G.

AU - Jones, Gwyneth

AU - Lamontagne, Francois

N1 - Funding Information: 1Department of Critical Care Medicine, Queen’s University, Kingston, ON, Canada. 2Department of Medicine, University of British Columbia, Vancouver, BC, Canada. 3Department of Biophysiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada. 4Centre de Recherche de l’Hôpital du Sacré-Coeur de Montréal, Critical Care and Medicine Departments, Université de Montréal, Montréal, QC, Canada. 5Department of Critical Care Medicine, Dalhousie University and the Nova Scotia Health Authority, Halifax, NS, Canada. 6Kingston General Hospital, Kingston, ON, Canada. 7Department of Critical Care Medicine, University of Ottawa, Ottawa, ON, Canada. 8Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada. The study was conceptualized by Dr. Muscedere. All authors contributed to the conduct of the study and/or provided input on the article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grants from the Lotte and John Hecht Memorial Foundation and South Eastern Academic Medical Association. The bovine lactoferrin was provided by Advanced Orthomolecular Research. The funders did not have any role in the conceptualization, conduct of the study, study analysis, interpretation of the data, or writing of the article. Dr. Muscedere, Dr. Maslove, Dr. Boyd, Ms. O’Callaghan, Dr. Reynolds, Dr. Hall, and Dr. Jones disclosed off-label product use of lactoferrin for the reduction of nosocomial infections. Dr. Boyd’s institution received funding from South Eastern Academic Medical Association (SEAMO) Innovation Fund and SEAMO New Clinician Scientist Award, and he received funding from Physician Services Incorporated New Clinician Science Award. Dr. Hall’s institution received funding from Queen’s University, Canadian Institutes for Health Research, and GlaxoSmithKline. Mr. Day’s institution received funding from Queen’s University Faculty of Health Sciences to Publisher Copyright: Copyright © 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

PY - 2018

Y1 - 2018

N2 - Objective: To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study. Design: Phase 2, multicenter, randomized, double-blind, placebocontrolled study. Setting: Medical-surgical ICUs. Patients: Adult, critically ill patients receiving invasive mechanical ventilation. Interventions: Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days. Measurements and Main Results: Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [sd], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; p = 0.91) and nosocomial infections (0.3 [0.7] vs 0.4 [0.6] per patient; p = 0.48) did not differ between lactoferrin and placebo groups, respectively. Clinical outcomes for lactoferrin versus placebo were as follows: ICU length of stay (14.5 [18.0] vs 15.0 [37.3] d; p = 0.82), hospital length of stay (25.0 [25.9] vs 28.1 [44.6] d; p = 0.57), hospital mortality (41.1% vs 30.5%; p = 0.11), and 90-day mortality (44.9% vs 32.4%; p = 0.06). Biomarker levels did not differ between the groups. Conclusions: 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.

AB - Objective: To obtain preliminary evidence for the efficacy of lactoferrin as a preventative measure for nosocomial infections and inform the conduct of a definitive study. Design: Phase 2, multicenter, randomized, double-blind, placebocontrolled study. Setting: Medical-surgical ICUs. Patients: Adult, critically ill patients receiving invasive mechanical ventilation. Interventions: Randomized, eligible, consenting patients expected to require invasive mechanical ventilation more than 48 hours received lactoferrin both enterally and via an oral swab or a placebo of sterile water for up to 28 days. Measurements and Main Results: Of the 214 patients who were randomized, 212 received at least one dose of the intervention and were analyzed (107 lactoferrin and 105 placebo). Protocol adherence was 87.5%. Patients receiving lactoferrin were older (mean [sd], 66.3 [13.5] vs 62.5 [16.2] yr), had a higher Acute Physiology and Chronic Health Evaluation II score (26.8 [7.8] vs 23.5 [7.9]), and need for vasopressors (79% vs 70%). Antibiotic-free days (17.3 [9.0] vs 18.5 [7.1]; p = 0.91) and nosocomial infections (0.3 [0.7] vs 0.4 [0.6] per patient; p = 0.48) did not differ between lactoferrin and placebo groups, respectively. Clinical outcomes for lactoferrin versus placebo were as follows: ICU length of stay (14.5 [18.0] vs 15.0 [37.3] d; p = 0.82), hospital length of stay (25.0 [25.9] vs 28.1 [44.6] d; p = 0.57), hospital mortality (41.1% vs 30.5%; p = 0.11), and 90-day mortality (44.9% vs 32.4%; p = 0.06). Biomarker levels did not differ between the groups. Conclusions: 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.

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Prevention of nosocomial infections in critically ill patients with lactoferrin: A randomized, double-blind, placebo-controlled study

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