John Muscedere1, David M Maslove1, J Gordon Boyd1, Nicole O'Callaghan1, Stephanie Sibley1, Steven Reynolds2,3, Martin Albert4, Richard Hall5, Xuran Jiang6, Andrew G Day6, Gwyneth Jones7, Francois Lamontagne8. 1. Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada. 2. Department of Medicine, University of British Columbia, Vancouver, BC, Canada. 3. Department of Biophysiology and Kinesiology, Simon Fraser University, Burnaby, BC, Canada. 4. Centre de Recherche de l'Hôpital du Sacré-Coeur de Montréal, Critical Care and Medicine Departments, Université de Montréal, Montréal, QC, Canada. 5. Department of Critical Care Medicine, Dalhousie University and the Nova Scotia Health Authority, Halifax, NS, Canada. 6. Kingston General Hospital, Kingston, ON, Canada. 7. Department of Critical Care Medicine, University of Ottawa, Ottawa, ON, Canada. 8. Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada.
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, 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.
RCT Entities:
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 illpatients 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.
Authors: Gabrielle Levin; J Gordon Boyd; Andrew Day; Miranda Hunt; David M Maslove; Patrick Norman; Nicole O'Callaghan; Stephanie Sibley; John Muscedere Journal: Intensive Care Med Exp Date: 2020-09-16