A Multi-centre Open Label Randomized Controlled Phase IIB Trial Comparing Vancomycin Versus Daptomycin for the Treatment of MRSA Bacteremia Due to Isolates With High Vancomycin Minimum Inhibitory Concentrations
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- All cause mortality
研究概览
简要总结
The aim of this study is to compare the efficacy of daptomycin treatment versus vancomycin treatment in the treatment of methicillin resistant staphylococcus aureus (MRSA) bloodstream infections (BSI) due to isolates with high vancomycin minimum inhibitory concentrations (MIC) (i.e. > or equal to 1.5 ug/ml) in terms of reducing all-cause mortality.
Our secondary aim is to compare clinical failure rates of daptomycin treatment versus vancomycin treatment and to compare time to microbiological clearance in patients treated with daptomycin versus those treated with vancomycin.
Our primary hypothesis is that Daptomycin treatment is superior to vancomycin treatment in reducing mortality from BSIs due to MRSA with high vancomycin MIC from 25% to 10%.
详细描述
Introduction/Clinical Significance Vancomycin is the standard first-line treatment for methicillin resistant Staphylococcus aureus (MRSA) bacteremia. In recent years however, there has been an increase in the number of MRSA isolates with high vancomycin minimum inhibitory concentrations (MIC). Recent consensus guidelines recommend clinicians consider using alternative agents such as daptomycin for MRSA infection when the vancomycin MIC is greater than 1 ug/ml. To date however, there has been no head to head randomized trial comparing the safety and efficacy of daptomycin and vancomycin in the treatment of blood stream infections (BSIs) due to MRSA with high vancomycin MICs.
Specific Aims:
Our primary aim is to compare the efficacy of daptomycin treatment versus vancomycin treatment in the treatment of MRSA BSIs due to isolates with high vancomycin MICs (i.e. > or equal to 1.5 ug/mL) in terms of reducing all-cause mortality.
Our secondary aim is to compare clinical failure rates of daptomycin treatment versus vancomycin treatment and to compare time to microbiological clearance in patients treated with daptomycin versus those treated with vancomycin.
Hypothesis:
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
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 21 years.
- •Inpatient at the time of enrolment.
- •MRSA bacteremia due to MRSA isolates with a vancomycin MIC > 1.5 ug/ml.
- •Be prepared to undergo all treatments and procedures, and attend follow-ups as per the trial protocol.
排除标准
- •Allergy to any of the study medications.
- •Pregnant or breastfeeding females.
- •Unable to provide consent or have no legally authorized representatives.
- •Currently enrolled or within the past three months participated in an interventional antibiotic or vaccine trial.
- •>48 hours after MRSA vancomycin MIC > or equal to1.5 ug/ml confirmation by the microbiology laboratory (assessed from time of lab report).
- •Patients on palliative care or with less than 24 hours of life expectancy (as discussed with their primary physicians).
- •Polymicrobial bacteremia [see (a) below].
- •Pneumonia [see (b) below].
- •On treatment with linezolid, tigecycline or ceftaroline immediately prior to enrolment.
- •Previous blood cultures positive for MRSA in the preceding one month.
- •On vancomycin or daptomycin treatment for more than 96 hours prior to enrolment.
- •BSI due to MRSA with vancomycin MIC > or equal to 4 ug/ml.
- •Baseline serum creatine kinase more than 1.5 times the upper limit of normal.
- •Patients with prosthetic heart valves
- •Any other significant condition that would, in the opinion of the investigator, compromise the patient's safety or outcome in the trial.
- •.Isolation of a significant organism other than MRSA from index blood cultures or blood cultures taken up to two weeks prior to enrolment and/or for which the patient is still on treatment.
- •.Chest x-ray at baseline consistent with pneumonia AND at least 2 of the following signs and symptoms: New onset or worsening cough, purulent sputum or increased suctioning requirements, dyspnea/tachypnea or respiratory rate > 30/min, hypoxemia or worsening gas exchange as determined by study investigator.)
研究组 & 干预措施
Daptomycin
Daptomycin will be dosed intravenously at 6-8mg/kg every 24 hours.
Patients with uncomplicated bacteremia will receive a dose of 6mg/kg every 24 hours. Patients with suspected complicated bacteremia or endocarditis, or receipt of at least two doses of vancomycin in the last 90 days (apart from vancomycin received for their current MRSA bacteremia) will receive a dose of 8mg/kg every 24 hours.
In patients with a creatinine clearance less than 30ml/min, or on intermittent or continuous hemodialysis, daptomycin will be dosed at 6-8mg/kg every 48 hours. The same criteria as above applies as to whether they receive 6mg/kg or 8mg/kg every 48hours. Daptomycin will be administered after hemodialysis in patients undergoing intermittent hemodialysis.
干预措施: Daptomycin (Drug)
Vancomycin
Vancomycin will be dosed at 15mg/kg every 12 hours with appropriate dose adjustments by a pharmacist in patients with a creatinine clearance less than 50 ml/min, so as to achieve a vancomycin trough level of 15-20ug/ml.
干预措施: Vancomycin (Drug)
结局指标
主要结局
All cause mortality
时间窗: 60 days
To compare the efficacy of daptomycin treatment versus vancomycin treatment in the treatment of MRSA BSIs due to isolates with high vancomycin MICs (i.e. \> or equal to 1.5 ug/L) in terms of reducing all-cause mortality 60 days from the time of index blood culture.
次要结局
- The need for an additional anti-MRSA agent due to worsening infection while on study treatment.(60 days)
- Time to microbiological clearance(60 days)
- Rates of nephrotoxicity(60 days)
- The need to stop the study drug due to toxicity(60 days)
- Rates of clinical failure(60 days)
- The need to discontinue study drug due to worsening infection(60 days)
- Rates of musculoskeletal toxicity(60 days)
- Adverse events in both treatment arms up to 60 days from index culture or 30 days post last study dose if later than the 60 day visit.(90 days)
- Serious adverse events at any time during the study period, whether or not they are thought to be related to the investigation drug.(60 days)