Early impact therapy with ceftazidime-avibactam via rapid diagnostics versus standard of care antibiotics and diagnostics in patients with bloodstream infection, hospital-acquired pneumonia or ventilator-associated pneumonia due to Pseudomonas aeruginosa or carbapenemase producing Enterobacterales
概览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- ADVANCE ID
- 入组人数
- 5,900
- 试验地点
- 1
- 主要终点
- Primary outcome is a composite measure in which any of the following occur:
概览
简要总结
Antimicrobial resistance is a growing public health threat and the key strategy to reduce mortality is to improve diagnostics and initiate early targeted antibiotic therapies. Conventional diagnostic methods take 3-5 days for bacterial identification and susceptibility tests. Rapid diagnostics detect associated antimicrobial resistance within hours and hence enabling early treatment. Though validated against EUCAST and CLSI standards, assimilation to routine clinical care is slow mainly due to the inadequate evidence to support the benefits of rapid diagnostics. The RAPID trial proposes a seamless intervention linking rapid bacterial isolate identification and antibiotic resistance gene detection and targeted antibiotic prescription to minimise time between infection onset and appropriate treatment. The primary hypothesis is the study interventions will lead to improved clinical outcomes compared to standard antibiotic susceptibility testing and treatment. This study is an open labelled non blinded randomised control trial. The primary study population will consist of patients with Pseudomonas aeruginosa or carbapenemase producing Enterobacterales bloodstream infections, hospital-acquired pneumonia and ventilator-associated pneumonia. Patients will be randomised to either a control or intervention arm. Patients randomised to the intervention arm will have relevant specimens analysed by rapid microbiological diagnostics and will have early availability of ceftazidime-avibactam with or without aztreonam if appropriate. Patients in the control arm will undergo routine standard of care diagnostics and treatment in accordance to the institutional policies as decided by the treating physician.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •a) At risk of bloodstream infections, hospital-acquired pneumonia or ventilator-associated pneumonia due to Pseudomonas aeruginosa or carbapenemase producing Enterobacterales; OR, b) whose blood culture bottles growing Gram negative bacilli; OR, c) who are suspected to have hospital-acquired pneumonia or ventilator-associated pneumonia and whose respiratory samples show Gram negative bacteria on Gram stain.
排除标准
- •a) Refractory shock or comorbid condition such that patient not expected to survive more than 48 hours; OR, b) where the bloodstream infection is thought to be related to a vascular catheter and the catheter is unable to be removed; OR, c) treatment is not with the intent to cure the infection; OR, d) patients previously randomised in this trial within the last 60 days.
结局指标
主要结局
Primary outcome is a composite measure in which any of the following occur:
时间窗: within 14 days from collection of index blood culture/respiratory culture
Patient has died from any cause; OR,
时间窗: within 14 days from collection of index blood culture/respiratory culture
SOFA score has not improved at Day 14 compared with baseline score on day of collection of index respiratory culture
时间窗: within 14 days from collection of index blood culture/respiratory culture
Modified SOFA will be used, if the full SOFA score cannot be calculated e.g. outside of the intensive care unit setting. If the study participant is discharged with improved clinical status prior to day 14, it will be assumed that SOFA score has improved. If the study participant is discharged with expected demise, it will be assumed that SOFA score has failed to improve.
时间窗: within 14 days from collection of index blood culture/respiratory culture
次要结局
- Clinical response as determined retrospectively by an adjudication committee
- All-cause mortality
- Days alive and out of hospital.(28 days from the date of index culture)
- Length of stay in ICU.
- Length of stay in hospital.
- Type of accommodation on discharge from hospital
- Duration of mechanical ventilation(28 days from date of index culture)
- Persistence of bacteremia
- Persistence of microbiologic growth of at least one organism growing from index respiratory culture
- Development of resistance to meropenem, colistin or ceftazidime-avibactam in any bacteria grown from clinically-indicated cultures(28 days from date of index culture)
- Development of acute kidney injury (KDIGO definitions).(28 days from date of index culture)
- Development of Clostridioides difficile diarrhea.(28 days from date of index culture)
- Time from index culture sample received by the laboratory to antibiotic therapy active in vitro (in hours)
- Number of days on antibiotics(total, and by antibiotic type)
- Percentage of patients undergoing modification of antibiotic therapy(7 days after microbiology diagnostics for the index culture)
- Time to detection of carbapenem resistance (in hours)
- Time to detection of resistance to ceftriaxone/cefotaxime (in hours)
- Time to detection of Acinetobacter baumannii calcoaceitcus complex or Stenotrophomonas maltophilia (in hours)(from index culture sample received by the laboratory)
- Functional outcome(at Day 14, Day 28 and Day 60 from collection of index culture)
- Composite outcome measure defined by Desirability of Outcome Ranking (DOOR)(at Day 28 from index culture sample)
研究者
Dr George M Varghese
Christian Medical College Vellore