Prevention of Nosocomial Infections in Critically Ill Patients With Lactoferrin: The PREVAIL Study
Condition: Critically Ill
MeSH terms: Infections; Cross Infection; Critical Illness
Study type: Interventional
Phase: Phase 2

Summary: 
      Lactoferrin is a protein that is a component of the immune system. It has many properties
      that could make it the ideal agent for the prevention of hospital-acquired infections.
      Lactoferrin has antibacterial properties (is able to kill or stop the growth of disease
      causing bacteria and fungal organisms), it improves immune function, and can increase the
      growth of beneficial bacteria in the bowel. Lactoferrin has been approved by Health Canada as
      a Natural Health product and is sold in health food stores as a supplement. However, given
      the potential beneficial effects of Lactoferrin, it requires further study as to its effects
      in acutely and seriously ill patients. One potential use which has not been studied is for
      the prevention of infections in critically adult ill patients. The aim of this study is to
      determine the utility of Lactoferrin in this patient population.

      The Lactoferrin that the investigators will be using in this study is extracted from cow's
      milk, where it naturally occurs. Cow lactoferrin has similar properties as that normally
      produced in the human body. This study is being conducted to determine how well a solution of
      Lactoferrin given orally and through a feeding tube helps to prevent infections and
      inflammation in critically ill patients in addition to usual care and other measures that are
      known to be partially effective for the prevention of infections.
    

Detailed description: 
      Hypothesis/Objectives

      Nosocomial infections are common in critically ill, mechanically ventilated patients and
      remain a source of morbidity and mortality in this vulnerable patient population. Multiple
      potential etiologies for the increased susceptibility to nosocomial infections have been
      posited including instrumentation for monitoring and treatment, alterations of immunological
      function, replacement of normal gastro-intestinal (GI) flora with pathogens and increased
      permeability of bowel mucosa. Current preventive measures are only partially effective but
      the most studied and most efficacious preventive measure for nosocomial infections is
      selective decontamination of the digestive tract (SDD) with antimicrobial therapy although it
      is rarely used secondary to concerns over the development of antimicrobial resistance. There
      is a need to study and utilize novel measures for SDD which maintain the benefits of SDD but
      minimize the negative consequences of increased antibiotic use driving antimicrobial
      resistance. Lactoferrin, a molecule which is part of the innate immune system has many
      properties that would make it the ideal agent for the prevention of nosocomial infections. It
      maintains GI integrity, has antibacterial properties, improves immune function, and has
      beneficial effects on the bacterial flora in the GI tract. As a result, the overall
      hypotheses and objectives of this research program are as follows:

      OVERALL HYPOTHESIS: The administration of oral and nasogastric Lactoferrin to critically ill
      mechanically ventilated patients will reduce nosocomial infections, reduce antibiotic usage,
      result in improved outcomes and improve survival.

      HYPOTHESIS for PHASE 2 Study: A Phase 2 randomized controlled trial to determine the
      effectiveness of Lactoferrin for the prevention of nosocomial infections will demonstrate
      that the utilization of Lactoferrin results in increased antibiotic free days and is
      supported by the biomarker and mechanistic data obtained.

      OBJECTIVES:

        1. Objective 1: The primary objective of this Phase 2, multicenter, randomized controlled
           trial (RCT) is to determine the effect of Lactoferrin on antibiotic free days. These
           data will inform a future large scale Phase 3 RCT powered on clinically important
           outcomes such as mortality.

        2. Objective 2: The second objective will be to assess the feasibility of conducting a
           future large scale Phase 3 RCT powered on clinically important outcomes.

        3. Objective 3: To obtain information on the effect of Lactoferrin on clinical outcomes
           including antibiotic utilization, nosocomial infections, length of stay, measures of
           organ dysfunction and mortality. This study will not be powered for the detection of
           clinically important differences but will inform power calculations for the definitive
           Phase 3 trial.

        4. Objective 4: To determine the effect of treatment with Lactoferrin on inflammatory
           biomarkers, immunological function, gastro-intestinal integrity and tracheal
           colonization.
    

Intervention name(s): Lactoferrin; Placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Lactoferrin is an 80 kilodalton (kD) naturally occurring multifunctional glycoprotein of the transferrin family which is an important component of the human innate immune system. Lactoferrin is distributed widely in humans with the main sources of production being exocrine glands and specific granules of neutrophils. It is present in virtually all human secretions. The highest concentrations are found in milk and colostrum. Lactoferrin has multiple biological functions which make it of interest as a therapeutic agent in the critically ill. These include the ability to bind iron, antimicrobial activity including antibacterial, antifungal, antiviral properties, the ability to bind endotoxin, promotion of beneficial bacteria in the gastro-intestinal tract and immunomodulatory activity.; Sterile water will be utilized as the placebo control in this double blind randomized-controlled trial.
Other intervention name(s): Sterile water
Intervention MeSH terms: Lactoferrin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Critically Ill; Intensive care; Nasogastric tube; Orogastric tube; mechanically ventilated; nosocomially acquired infections; length of stay; lactoferrin; placebo controlled; antibiotic free days