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

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, placebo-controlled 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. 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 (https://ift.tt/29S62lw). 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 Kingston General Hospital Research Institute. The remaining authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: muscedej@kgh.kari.net Copyright © by 2018 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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