A Phase 2 Randomized Controlled Trial to Determine the Efficacy of Lactoferrin for the Prevention of Nosocomial Infections.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 214
- 试验地点
- 1
- 主要终点
- Antibiotic free days.
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (>18 years old)
- •Duration of mechanical ventilation < 48 hours and
- •Expected duration of mechanically ventilation > 72 hours.
排除标准
- •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)
- •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.
研究组 & 干预措施
Placebo (sterile water)
Placebo (sterile water) will also be delivered down the nasogastric tube; administered in 4 divided doses per day.
干预措施: Placebo (Other)
Lactoferrin
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.
干预措施: Lactoferrin (Dietary Supplement)
结局指标
主要结局
Antibiotic free days.
时间窗: 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.
次要结局
- Feasibility of conducting a Phase 3 study powered on clinically important outcomes such as mortality, length of stay and duration of mechanical ventilation.(90 days post study enrollment.)
研究者
Dr. John Muscedere
Dr. John G. Muscedere, MD, FRCPC
Queen's University