Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness: A Pilot RCT
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 18
- 主要终点
- Adherence to treatment duration protocol (proportion of treatment courses)
研究概览
简要总结
Bacteremia is a leading cause of mortality and morbidity in critically ill adults. Although bacteria in the bloodstream (bacteremia) may arise from variable infectious foci (most commonly central vascular catheter related, lung, urinary tract, intra-abdominal, or skin and soft tissue sources), because of the high attendant morbidity and mortality of bacteremia, these patients collectively represent a critically important group to study.
The consequences of the excessive antimicrobial use for individual patients, range from rash, gastrointestinal upset and diarrhea, to anaphylaxis, neutropenia, renal failure, toxic epidermal necrolysis, death, and a marked increase in ICU and hospital drug costs. One particularly concerning complication, Clostridium difficile infection, has increased in incidence and severity over the past decade. Much of this burden could be prevented through reduction in unnecessary antibiotic use.
Another major consequence of excessive antibiotic use is antimicrobial resistance. Antibiotic resistance is not only a concern for the patient who receives antibiotics, but also for neighbouring patients in the ICU, as well as future patients in the ICU and the hospital at large - through patient-to-patient transmission, and environmental contamination.
No previous randomized controlled trials have directly compared shorter versus longer durations of antimicrobial treatment in these patients. The investigators will conduct a multi-center randomized concealed allocation trial of shorter duration (7 days) versus longer duration (14 days) antibiotic treatment for critically ill patients with bacteremia admitted to ICU. Eligible, patients will be randomized to either 7 days or 14 days of adequate antimicrobial treatment. The selection of type, dose and route of antibiotics will be at the discretion of the treating physicians, but the duration of treatment (7 versus 14 days) will be determined by randomization group. The randomization assignment will not be communicated to the study research coordinator, study critical care or infectious diseases investigators or clinicians until day 8. The primary outcome for the main trial will be 90-day mortality.
The study will be initiated at Sunnybrook Health Sciences Centre in Toronto, Ontario, and then rolled out to a second site at Kingston General Hospital in Kingston, Ontario. These sites will be sufficient to meet the sample size goals for the pilot RCT, but if additional funds are obtained the investigators will also roll out to the other Canadian ICUs listed below. The goal of adding these additional sites will be to increase the generalizability of the findings with respect to trial feasibility
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is in the ICU at time the blood culture result reported as positive AND
- •Patient has a positive blood culture with pathogenic bacteria.
排除标准
- •Patient already enrolled in the trial
- •Patient has severe immune system compromise, as defined by: absolute neutrophil count <0.5x109/L; or is receiving immunosuppressive treatment for solid organ or bone marrow or stem cell transplant
- •Patient has syndrome with well-defined requirement for prolonged treatment:
- •infective endocarditis
- •osteomyelitis/septic arthritis
- •undrainable/undrained abscess
- •unremovable/unremoved prosthetic-associated infection
- •Patient has a single positive blood culture with a common contaminant organism according to Clinical Laboratory & Standards Institute (CLSI) Guidelines: coagulase negative staphylococci; or Bacillus spp.; or Corynebacterium spp.; or Propionobacterium spp.; or Aerococcus spp.; or Micrococcus spp.
- •Patient has a positive blood culture with Staphylococcus aureus.
- •Patient has a positive blood culture with Candida spp. or other fungal species.
研究组 & 干预措施
7 days
Patients in 7 day arm will receive adequate antibiotics until the end of day 7 only
干预措施: 7 days of adequate antibiotic treatment durations (Other)
14 days
Patients in 14 day arm will receive adequate antibiotics until the end of day 14 only
干预措施: 14 days of adequate antibiotic treatment durations (Other)
结局指标
主要结局
Adherence to treatment duration protocol (proportion of treatment courses)
时间窗: 15 days
We will consider the main trial to be feasible and worthy of embarking on a larger mortality-powered RCT if 90% of antibiotic treatment courses are within 7± 2 days in the shorter duration treatment arm or 14 ± 2 days in the longer duration treatment arm.
Rate of recruitment (patients per site, per month)
时间窗: For up to 1 year
We will consider the main trial to be feasible if we achieve recruitment rates of at least 1 patient per 4 weeks, on average, per participating site.
次要结局
- Hospital lengths of stay(For the duration of Hospital stay, expected for an average of 30 days assessed up to 1 year.)
- Hospital mortality(recorded as alive or dead at hospital discharge following index positive blood culture for an expected average of 4 weeks assesses upto one year.)
- 90 day mortality(Recorded as alive or dead at 90 days following index positive blood culture)
- Antimicrobial-related acute kidney injury(Up to 30 days from start of antibiotic treatment)
- Antimicrobial-related hepatitis(Up to 30 days from start of antibiotic treatment)
- ICU mortality(Recorded as alive or dead at ICU discharge following index positive blood culture for an expected average of 2 weeks assesses upto one year.)
- Relapse rates of bacteremia(Upto 30 days after adequate antibiotic treatment)
- Rates of Clostridium difficile infection in hospital(Upto 30 days after index blood culture collection date)
- Anaphylaxis(Up to 30 days from start of antibiotic treatment)
- Rates of secondary nosocomial infection with antimicrobial resistant organisms in hospital(Upto 30 days after index blood culture collection date)
- Antibiotic allergy(Up to 30 days from start of antibiotic treatment.)
- ICU lengths of stay(For the duration of ICU stay, expected for an average of 30 days assessed up to 1 year.)
- Mechanical ventilation duration(For the duration of ICU and Hospital stay, expected for an average of 30 days)
- Vasopressor duration in ICU(For the duration of ICU and Hospital stay, expected for an average of 30 days)
研究者
Dr. Nick Daneman
Clinician Scientist
Sunnybrook Health Sciences Centre