Probiotic Prophylaxis for Microbiome Modulation and Ventilator Associated Pneumonia (VAP) or Severe Infections Prevention in Multitrauma Patients: a Multicenter, Randomized, Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 2
- 主要终点
- Probiotics for VAP prophylaxis
研究概览
简要总结
Ventilator-associated pneumonia (VAP), is a type of pneumonia that develops more than 48 hours after endotracheal intubation, is common in intensive care units (ICUs). It is estimated to be responsible for 27% to 47% of ICU-acquired infections.
The pathogenesis of VAP is complex but typically involves colonization of the aerodigestive tract with pathogenic bacteria, the formation of biofilms, and microaspiration of contaminated secretions. Preventing carriage of potentially pathogenic micro-organisms from the aerodigestive tract is an infection control strategy used to reduce the occurrence of VAP. One novel intervention is the administration of prophylactic probiotics which restore non-pathogenic flora that compete with pathogens, modulate local and systemic immunity, and decrease intestinal permeability and thus can be beneficial in preventing nosocomial infections in critically ill patients. The role of the probiotics in preventing VAP in mechanically ventilated patients is inconclusive. Some evidence indicates that probiotics may reduce the incidence of VAP by inhibiting pathogen adhesion, improving gut mucosal barrier function, reducing bacterial translocation and up-regulating the immune system. Furthermore, guidelines remain inconclusive regarding the role of commensal oropharyngeal flora (COF) as a causative agent in VAP, mainly due to a scarcity of studies in this research field. However, there is evidence that COF may cause pulmonary infection, mostly in immunocompromised patients.
详细描述
The oropharyngeal swab will be collected on days 1, 3 and 7 after ICU admission and upon the occurrence of VAP or other infection. Nonbronchoscopic bronchoalveolar lavage (BAL) using a protected catheter will be collected on day 3 after ICU admission and upon the occurrence of VAP. Whole blood sample and stool sample will be collected on day 1 after ICU admission and upon the occurrence of VAP or other infection for microbiome analysis.
As soon as the first sample of the oropharyngeal swab is collected, patients will be allocated to the "treatment" groups. Each patient will receive two capsules per day for 15 consecutive days post admission. The content of one capsule will be suspended in 100ml tap water and administered by nasogastric tube or through), while the content of the other capsule will be suspended in sterile, water-based surgical lubricant and administered as a slurry to the oropharynx. The administration will be performed by a study nurse who was responsible for ascertaining that the whole prepared volume is given.
The study protocol-mandated baseline data will include demographic information, medical history, and the APACHE II, SAPS II, NISS and SOFA score, and Operative POSSUM score (only cases undergoing surgical treatment).
Additional information collected on a daily basis will include patient's clinical course with special emphasis on clinical signs of VAP or infections, type of chemoprophylaxis, endotracheal or tracheostomy tube cuff pressure, type of nutrition and bowel movement. Furthermore, duration of intubation, tracheostomy day after ICU admission, duration of mechanical ventilation, lengths of stay in the ICU and hospital, adverse events (related and non-related to probiotics administration) and mortality. Data recording will be extended up to 30 days after hospital admission (patient recovered, treated in ICU / department or death).
Central venous line infection will be considered as positive when there is bacteremia with common skin commensal and positive catheter tip culture or exit site culture for the same organism.
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)
盲法说明
A numbered sealed envelope will be used to ensure blinding. Only the pharmacist responsible for the sealed envelopes preparation will be aware of its content, with no further involvement in the study protocol.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •adults >18 and < 80 years oldmultitrauma patients with at least two organ-system injury
- •intubated immediately after injury
- •likelihood that the patient would require mechanical ventilation with an endotracheal tube (or tracheostomy) for >10 days
- •life expectancy > 15 days
排除标准
- •investigators unable to obtain informed written consent from patients' relatives
- •administer the first dose of the study drug within 24 hours of intubation
- •pregnancy; lactation; immunosuppression; hematologic disease; prosthetic cardiac valve or vascular graft; cardiac trauma; history of rheumatic fever, endocarditis, or congenital cardiac abnormality; oropharyngeal mucosal injury; recent history of sinusitis and respiratory tract infection
- •obesity [BMI > 40]
- •administration of antibiotics for > 3 days before recruitment into the study
- •administration of probiotics before recruitment into the study
- •history of infection from Hepatis B or C and HIV
- •administration of < 90% of the predicted doses of probiotics during the study period
结局指标
主要结局
Probiotics for VAP prophylaxis
时间窗: 30 days
To determine the efficacy of probiotic administration for the prophylaxis of VAP in a multi trauma population admitted in the ICU This outcome will be assessed by the difference of number of cases (n) and percentage of change (%) in VAP development between probiotics and control groups Ventilator associated pneumonia (VAP) will be defined as pneumonia developing more than 48 h after endotracheal intubation and initiation of mechanical ventilation. The diagnostic criteria for VAP will be the following: * SOFA score elevation of at least 1 point * New or progressive radiographic consolidation or infiltrate. In addition, at least 2 of the following: * Temperature \> 38 °C * Leukocytosis (white blood cell count ≥ 12,000 cells/ mm3) or leukopenia (white blood cell count \< 4,000 cells/mm3) * Presence of purulent secretions * BAL \> 104 colony forming units (CFU)/ml)
次要结局
- Probiotics for bacteremia, sepsis or septic shock reduction(30 days)
- Probiotics for indections control(30 days)
研究者
Georgia Tsaousi
Assistant Professor
Aristotle University Of Thessaloniki