Polymyxin B Monotherapy Versus Polymyxin B-Carbapenem Combination Therapy in Critically Ill Patients With Multi-drug Resistant Gram-negative Infection: A Prospective, Parallel-Group, Double-Blind, Randomized Controlled Study
试验速览
- 阶段
- 3 期
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Resolution of the evidence of clinical infection
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of polymyxin B as monotherapy versus a combined polymyxin B-carbapenem therapy against multidrug-resistant (MDR) gram negative infections. The investigators intend to evaluate if this synergistic drug regimen correlates with improved outcomes against gram-negative infections in critically ill patients including: better clinical resolution, reduced length of stay at hospital, reduced length of stay at the intensive care unit, and less recurrence of infection.
详细描述
The "MUSEUM" trial is a single-center, prospective, parallel-group, double-blind, randomized, controlled study design. The trial will be conducted at the Intensive Care Unit of the Puerto Rico Trauma Hospital located in San Juan, Puerto Rico. Patients with clinical and microbiological evidence of an Multi-drug resistant infection related to Hospital-acquired pneumonia (HAP), Ventilator-associated pneumonia (VAP), Complicated Urinary tract infection (cUTI) or Bloodstream infection (BSI) will be considered candidates for the study. The pathogen should be resistant to all antibiotics except to polymyxin B. With a predicted survival rate of 67% (hazard ratio of 0.33), a significance of α = 0.05, power of 80%, and assuming a dropout rate of 15%, the estimated sample size is n = 40 patients (20 per group). In terms of safety, the most clinically relevant adverse effects are nephrotoxicity and neurotoxicity, which will be evaluated and adjudicated. The recurrence of infection will be defined as a new superinfection by the same or other species than the initial infection that is multidrug-resistant. Length of stay at the Hospital will be measured from the day of admission until the day of discharge. Length of stay in the ICU will be measured from the day of admission until the day of discharge from the unit. To our knowledge, this will be the first prospective, double blind, randomized, controlled clinical trial in representation of the critically ill trauma patients infected with Multi-drug resistant pathogens.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double blind, Double dummy
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •21 years or older admitted to the Intensive Care Unit of the Puerto Rico Trauma Hospital ° Consent form signed,
- •Clinical and microbiological evidence of a MDR infection related to HAP, VAP, cUTI or BSI.
- •The pathogen should be resistant to almost all antibiotics, AND/OR intermediate resistant to some of the antibiotics, AND/OR susceptible only to a class of antibiotic (i.e. aminoglycosides which are NOT recommended as monotherapy), AND/OR the clinician decision is to start the patient on polymyxin B due to severity of the infection.
- •Patient with a diagnosis of MDR infection, who have not received antibiotics at all; OR if received would be < 72 hours with polymyxin B or imipenem at/or after the diagnosis of MDR AND/OR at the time of randomization
- •Have a life expectancy of > 24 hours according to the attending physician's criteria.
排除标准
- •Pregnant woman
- •Prisoners
- •Severe hepatic failure (defined by serum conjugated bilirubin > 3 mg/dL)
- •End-stage renal disease requiring hemodialysis
- •Hypersensitivity to any study drug
- •Septic shock at the moment of randomization
- •Died within 48 hours of starting the study
研究组 & 干预措施
Polymyxin B monotherapy
Intravenous piggyback with Polymyxin B and control(Normal saline)
干预措施: Polymyxin B (Drug)
Polymyxin B plus Carbapenem
Intravenous piggyback with Polymyxin B plus Carbapenem
干预措施: Polymyxin B (Drug)
结局指标
主要结局
Resolution of the evidence of clinical infection
时间窗: 7-14 days, according to site of infection
Resolution of infection will be subjective to clinical criteria of the physician, AND patient has to be afebrile (temperature \< 38°C), or normothermic (temperature 36-37.5°C), AND have white blood cell count within normal limits (\> 4,000 and \< 10,000 cells/mm3).
次要结局
- 30-day mortality(30 days)
- Recurrence of infection(30 days)
- Length of stay at Hospital(30 days)
- Length of stay at ICU.(30 days)