CAMERA 2 - Combination Antibiotic Therapy for Methicillin Resistant Staphylococcus Aureus Infection - An Investigator-initiated, Multi-centre, Parallel Group, Open Labelled Randomised Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 358
- 试验地点
- 30
- 主要终点
- Complication-free 90 day survival
研究概览
简要总结
The aim of this clinical trial is to determine whether a novel combination antibiotic treatment (vancomycin/daptomycin + beta-lactam) is superior to the standard antibiotic treatment (vancomycin/daptomycin) for hospitalised adults with Methicillin Resistant Staphylococcus aureus bacteraemia. The hypothesis is that the addition of beta-lactam antibiotics (these are antibiotics from the penicillin family) to the standard therapy will lead to more efficient bacterial killing and hence lead to faster clearance of bacteria from the blood stream and other areas of infection, thereby reducing the risk of the spread of infection and death.
The study design is an investigator-initiated, multi-centre, open-label, randomised controlled trial. This will include 440 participants diagnosed with Methicillin Resistant Staphylococcus aureus bacteraemia recruited over a period of 4 years (July 2015 - June 2019) from within Infectious Diseases inpatient units across 21 hospital sites including 18 from within Australia and 3 located in Singapore. Participation will be voluntary and subject to informed consent. The participants will be randomised 1:1 to either the standard therapy group or combination therapy group. The combination therapy will include a treatment of intravenous beta-lactam for the first 7 days of treatment, in addition to the standard treatment (either vancomycin or daptomycin). The primary outcome measure will be complication-free survival 90 days post randomisation.
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
- Single (Outcomes Assessor)
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
- •Age >= 18 years.
- •≥1 set of blood cultures positive for MRSA
- •Able to be randomized within 72 hours of blood cultures being collected.
- •Likely to remain as inpatient for 7 days following randomization
排除标准
- •Previous type 1 hypersensitivity reaction to ß-lactams
- •Polymicrobial bacteraemia (not counting contaminants)
- •Previous participation in the trial
- •Known pregnancy
- •Current β-lactam antibiotic therapy which cannot be ceased or substituted
- •Participant's primary clinician unwilling to enrol patient
- •Moribund (expected to die in next 48 hours with or without treatment)
- •Treatment limitations which preclude the use of antibiotics Note that we are NOT planning to exclude participants with renal failure.
研究组 & 干预措施
Standard therapy + Beta-Lactam
In addition to standard treatment an intravenous Beta-Lactam (β-lactam) will be added for the first 7 calendar days following randomisation (randomisation is day 1 - hence patients will receive 6-7 days of β-lactam). This β-lactam will be intravenous flucloxacillin 2g every 6 hours in Australia and intravenous cloxacillin 2g every 6 hours in Singapore. For those with a history of minor allergy to any penicillin (rash or unclear history, but not anaphylaxis or angiooedema), it will be intravenous cefazolin 2g every 8 hours. For haemodialysis patients, it will usually be cefazolin 2g three times per week post dialysis, however clinicians are also free to choose intermittent (flu)cloxacillin, dosed as for glomerular filtration rate (GFR ) <10, if they desire.
干预措施: Beta-Lactam (Drug)
结局指标
主要结局
Complication-free 90 day survival
时间窗: Time period from randomisation (day 1) to day 90
Composite outcome at 90 days - any of: 1. All-cause mortality 2. Persistent bacteraemia at day 5 or beyond 3. Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture 4. Microbiological treatment failure. Positive sterile site culture for MRSA at least 14 days after randomisation.
次要结局
- All-cause mortality at days 14, 42 and 90 days(Time period from randomisation (day 1) to day 90)
- Persistent bacteraemia at day 5 or beyond(Time period from randomisation (day 1) to day 90)
- Acute kidney injury defined as ≥ stage 1 modified RIFLE criteria at any time within the first 7 days, OR new need for renal replacement therapy at any time from days 1 to 90. Excludes participants already on haemodialysis.(Time period from randomisation (day 1) to day 90)
- Microbiological treatment failure. Positive sterile site culture for MRSA at least 14 days after randomisation(Time period from randomisation (day 1) to day 90)
- Persistent bacteraemia at day 2(Time period from randomisation (day 1) to day 90)
- Microbiological relapse - positive blood culture for MRSA at least 72 hours after a preceding negative culture(Time period from randomisation (day 1) to day 90)
- Duration of intravenous antibiotic treatment(Time period from randomisation (day 1) to day 90)
- Direct health care costs(Time period from randomisation (day 1) to day 90)