Critically IllPhase 2PREVAILNCT01996579
Prevention of Nosocomial Infections in Critically Ill Patients With Lactoferrin: The PREVAIL Study
A Phase 2 study testing Lactoferrin in people with Critically Ill, run by Queen's University at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Critically Ill
- What is being tested?
- Lactoferrin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 214 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2013to 12 Sep 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (>18 years old)
- Duration of mechanical ventilation < 48 hours and
- Expected duration of mechanically ventilation > 72 hours.
Who cannot join
- Patients not expected to be in ICU for more than 72 hours from time of randomization (due to imminent death, withdrawal of aggressive care or discharge).
- The presence of a contra-indication to enteral feeding.
- Lack of access to the oral cavity.
- Allergy or sensitivity to Lactoferrin or bovine derived proteins or bovine milk
- Immunocompromised patients (post-organ transplantation, Acquired Immunodeficiency Syndrome [AIDS], neutropenia [<1000 absolute neutrophils], corticosteroids [>20 mgs/day of prednisone or equivalent for more than 6 months])
- Patients with fulminant liver failure or end stage liver disease (Child's Class C)
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- Life expectancy, due to pre-existing conditions such as cancer, is less than six months.
- Women who are pregnant or lactating.
- Enrollment in industry sponsored interventional trial (co-enrollment in other academic studies would be allowed with the proviso that there was no potential interaction between the protocols).
- Prior randomization in this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2 Randomized Controlled Trial to Determine the Efficacy of Lactoferrin for the Prevention of Nosocomial Infections.
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.
Read the 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:
- 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.
- 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.
- 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.
- Objective 4: To determine the effect of treatment with Lactoferrin on inflammatory biomarkers, immunological function, gastro-intestinal integrity and tracheal colonization.
- Conditions
- Critically Ill
- Being tested
- Lactoferrin, Placebo
- Keywords
- Critically Ill, Intensive care, Nasogastric tube, Orogastric tube, mechanically ventilated, nosocomially acquired infections, length of stay, lactoferrin, placebo controlled, antibiotic free days
- Medical subject headings
- Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LactoferrinDietary supplement
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.
PlaceboOther
Also called Sterile water
Sterile water will be utilized as the placebo control in this double blind randomized-controlled trial.
| Study group | Role | What they receive |
|---|---|---|
| Lactoferrin | Experimental | Patients randomized to the Lactoferrin arm will receive Lactoferrin delivered to the oral cavity as a mouth swab and Lactoferrin down a nasogastric tube; a total of 2 grams administered in 4 divided doses per day. Receives: Dietary Supplement: Lactoferrin |
| Placebo (sterile water) | Placebo comparator | Placebo (sterile water) will also be delivered down the nasogastric tube; administered in 4 divided doses per day. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Antibiotic free days.
Alive and free of antibiotics in the 28 days after study enrollment. These data will inform a future large scale Phase 3 RCT powered on clinically important outcomes such as mortality.
Measured: 28 Days after study enrollment.
Secondary outcomes (1)
Feasibility of conducting a Phase 3 study powered on clinically important outcomes such as mortality, length of stay and duration of mechanical ventilation.
Feasibility will be assessed on recruitment rates and acceptability/adherence to the study protocol.
Measured: 90 days post study enrollment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Nov 2013 (estimated)
- Study startNov 2013
- Primary completion12 Sep 2016
- Study completion12 Sep 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critically IllStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 214 participants (actual)
Sponsor and investigators
- Lead sponsor
- Queen's University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. John Muscedere, Queen's University
- Investigators
- John G Muscedere, MD, Principal investigator, Queen's University, Kingston General Hosptial
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01996579
- Sponsor's protocol ID
- DMED-1569-13
- Acronym
- PREVAIL
- Status last verified
- Feb 2017
- First submitted
- 18 Nov 2013
- Last updated
- 20 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Upon request only
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized Controlled Trial to Determine the Efficacy of Lactoferrin for the Prevention of Nosocomial Infections.
- ClinicalTrials.gov ID
- NCT01996579
- Acronym / sponsor ID
- PREVAIL / DMED-1569-13
- Conditions
- Critically Ill
- Keywords
- Critically Ill, Intensive care, Nasogastric tube, Orogastric tube, mechanically ventilated, nosocomially acquired infections, length of stay, lactoferrin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 214 participants (actual)
- Lead sponsor
- Queen's UniversityUniversity, hospital or other
- Study start
- Nov 2013
- Primary completion
- 12 Sep 2016 (actual)
- Study completion
- 12 Sep 2016 (actual)
- First posted
- 27 Nov 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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.
- 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.
- Objective 4: To determine the effect of treatment with Lactoferrin on inflammatory biomarkers, immunological function, gastro-intestinal integrity and tracheal colonization.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lactoferrin | Experimental | Dietary Supplement: LactoferrinPatients randomized to the Lactoferrin arm will receive Lactoferrin delivered to the oral cavity as a mouth swab and Lactoferrin down a nasogastric tube; a total of 2 grams administered in 4 divided doses per day. |
| Placebo (sterile water) | Placebo comparator | Other: PlaceboPlacebo (sterile water) will also be delivered down the nasogastric tube; administered in 4 divided doses per day. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult patients (>18 years old)
- Duration of mechanical ventilation < 48 hours and
- Expected duration of mechanically ventilation > 72 hours.
Key exclusion criteria (10 listed)
- Patients not expected to be in ICU for more than 72 hours from time of randomization (due to imminent death, withdrawal of aggressive care or discharge).
- The presence of a contra-indication to enteral feeding.
- Lack of access to the oral cavity.
- Allergy or sensitivity to Lactoferrin or bovine derived proteins or bovine milk
- Immunocompromised patients (post-organ transplantation, Acquired Immunodeficiency Syndrome [AIDS], neutropenia [<1000 absolute neutrophils], corticosteroids [>20 mgs/day of prednisone or equivalent for more than 6 months])
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LactoferrinLactoferrin 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. | Dietary supplement | Lactoferrin |
| PlaceboAlso: Sterile waterSterile water will be utilized as the placebo control in this double blind randomized-controlled trial. | Other | Placebo (sterile water) |
Primary outcome
Antibiotic free days.
Time frame: 28 Days after study enrollment.
Alive and free of antibiotics in the 28 days after study enrollment. These data will inform a future large scale Phase 3 RCT powered on clinically important outcomes such as mortality.
1 secondary outcome
Feasibility of conducting a Phase 3 study powered on clinically important outcomes such as mortality, length of stay and duration of mechanical ventilation.
Time frame: 90 days post study enrollment.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2017.
- Individual participant dataSharing planned: Yes. Upon request only
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John G Muscedere, MD principal investigator
Queen's University, Kingston General Hosptial
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lactoferrin in people with Critically Ill, run by Queen's University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Antibiotic free days. (time frame: 28 Days after study enrollment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2017.