Prevention of nosocomial infections in critically ill patients with lactoferrin (PREVAIL study): study protocol for a randomized controlled trial.
BACKGROUND
Nosocomial infections remain an important source of morbidity, mortality, and increased health care costs in hospitalized patients. This is particularly problematic in intensive care units (ICUs) because of increased patient vulnerability due to the underlying severity of illness and increased susceptibility from utilization of invasive therapeutic and monitoring devices. Lactoferrin (LF) and the products of its breakdown have multiple biological effects, which make its utilization of interest for the prevention of nosocomial infections in the critically ill.


METHODS
This is a phase II randomized, multicenter, double-blinded trial to determine the effect of LF on antibiotic-free days in mechanically ventilated, critically ill, adult patients in the ICU. Eligible, consenting patients will be randomized to receive either LF or placebo. The treating clinician will remain blinded to allocation during the study; blinding will be maintained by using opaque syringes and containers. The primary outcome will be antibiotic-free days, defined as the number of days alive and free of antibiotics 28 days after randomization. Secondary outcomes will include: antibiotic utilization, adjudicated diagnosis of nosocomial infection (longer than 72 h of admission to ICU), hospital and ICU length of stay, change in organ function after randomization, hospital and 90-day mortality, incidence of tracheal colonization, changes in gastrointestinal permeability, and immune function. Outcomes to inform the conduct of a larger definitive trial will also be evaluated, including feasibility as determined by recruitment rates and protocol adherence.


CONCLUSIONS
The results from this study are expected to provide insight into a potential novel therapeutic use for LF in critically ill adult patients. Further, analysis of study outcomes will inform a future, large-scale phase III randomized controlled trial powered on clinically important outcomes related to the use of LF.


BACKGROUND
The trial was registered at www.ClinicalTrials.gov on 18 November 2013.


BACKGROUND
NCT01996579 .
Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada. muscedej@KGH.KARI.NET.|Kingston General Hospital, Room 5-411, Angada 4, 76 Stuart Street, Kingston, ON, K7L 2 V3, Canada. muscedej@KGH.KARI.NET.
John
J
Muscedere
Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
David
D
Maslove
Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
John Gordon
JG
Boyd
Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
Nicole
N
O'Callaghan
Centre de recherché du CHU de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada.
Francois
F
Lamontagne
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
Steven
S
Reynolds
Centre de Recherche de l'Hôpital du Sacré-Coeur de Montréal, Division of Critical Care Medicine, Critical Care and Medicine Departments, Université de Montréal, Montréal, QC, Canada.
Martin
M
Albert
Department of Critical Care Medicine, Dalhousie University and the Nova Scotia Health Authority, Halifax, NS, Canada.
Rick
R
Hall
Department of Critical Care Medicine, Queen's University, Kingston, ON, Canada.
Danielle
D
McGolrick
Kingston General Hospital, Room 5-411, Angada 4, 76 Stuart Street, Kingston, ON, K7L 2 V3, Canada.
Xuran
X
Jiang
Kingston General Hospital, Room 5-411, Angada 4, 76 Stuart Street, Kingston, ON, K7L 2 V3, Canada.
Andrew G
AG
Day
Antibiotics; Critically ill; Intensive care; Lactoferrin; Mechanically ventilated patients; Mortality; Nosocomial infections
FEMS Immunol Med Microbiol. 2001 Aug;31(2):145-52
11549422
Crit Care Med. 2015 Sep;43(9):1832-8
26010687
J Med Microbiol. 1998 Sep;47(9):837-42
9736166
Nature. 2002 May 30;417(6888):552-5
12037568
Intensive Care Med. 1994 Nov;20 Suppl 4:S7-11
7699156
Am J Infect Control. 2012 Jun;40(5):396-407
21908073
Nutr Res. 2008 Sep;28(9):583-9
19083463
Med Care. 2010 Nov;48(11):1026-35
20940650
JAMA. 2009 Oct 7;302(13):1421-8
19809023
APMIS. 1991 Dec;99(12):1142-50
1772651
Biometals. 2004 Jun;17(3):279-83
15222478
Infect Immun. 1998 Jun;66(6):2434-40
9596699
J Crit Care. 2008 Mar;23(1):126-37
18359430
Crit Care Med. 2002 Aug;30(8):1772-7
12163791
Antimicrob Agents Chemother. 2009 Aug;53(8):3308-16
19451301
Am J Clin Nutr. 2007 Mar;85(3):816-23
17344505
Am J Respir Crit Care Med. 1998 Aug;158(2):444-51
9700119
J Nutr. 2001 Aug;131(8):2121-7
11481405
Jpn J Antibiot. 1993 Jun;46(6):482-5
8360983
Eur J Clin Microbiol Infect Dis. 2016 Feb;35(2):201-5
26610337
Biochem Cell Biol. 2012 Jun;90(3):233-44
22540735
Infect Immun. 2001 Mar;69(3):1469-76
11179314
Contemp Clin Trials. 2013 Jul;35(2):33-9
23608625
J Nutr. 2002 Sep;132(9):2597-600
12221215
Science. 1974 May 31;184(4140):952-6
4596821
Crit Care Med. 2009 May;37(5):1634-41
19325489
Peptides. 2005 Dec;26(12):2355-9
15979203
APMIS. 1997 Nov;105(11):875-83
9393559
Intensive Care Med. 2003 Apr;29(4):530-8
12664219
Cell Mol Life Sci. 2005 Nov;62(22):2588-98
16261252
Chest. 1995 Aug;108(2 Suppl):1S-16S
7634921
Clin Infect Dis. 2011 May;52(9):e162-93
21460264
Infect Dis Clin North Am. 2009 Sep;23(3):727-43
19665092
Pediatr Clin North Am. 2008 Jun;55(3):647-68, xi
18501759
Crit Care Med. 2013 Jan;41(1):15-23
23222254
Intensive Care Med. 1996 Jul;22(7):707-10
8844239
Biometals. 2004 Jun;17(3):285-9
15222479
Int J Antimicrob Agents. 2008 Feb;31 Suppl 1:S68-78
18006279
Helicobacter. 2009 Apr;14(2):119-27
19298339
Med Care. 2008 Jan;46(1):101-4
18162862
J Nutr. 2001 Aug;131(8):2101-4
11481401
Chest. 2001 Dec;120(6):2059-93
11742943
Biochem Cell Biol. 2012 Jun;90(3):245-51
22574842
J Clin Invest. 1991 Oct;88(4):1080-91
1918365
J Anim Physiol Anim Nutr (Berl). 2007 Apr;91(3-4):109-19
17355340
Clin Chem. 2002 Nov;48(11):1883-90
12406972