TREAT-GNB [CR-GNB]
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 41
- 主要终点
- Clinical outcome
研究概览
简要总结
TREAT-GNB is an innovative trial to expedite the evaluation of various antibiotic choices and treatment strategies for severe multidrug-resistant Gram-negative bacterial infections, specifically bloodstream and lower respiratory tract infections. This approach combines platform trial elements with adaptive clinical designs to streamline the evaluation of various treatment options and optimise resource utilisation. The overall aim of the TREAT-GNB platform trial is to identify interventions that improve survival in patients with severe infections due to Gram-negative bacteria.
In the CR-GNB silo of TREAT-GNB, the primary objective is to quantify the effect on all-cause mortality at 28 days of a range of interventions in patients with bloodstream infections, ventilator-associated pneumonia, and hospital-acquired pneumonia caused by CR-GNB.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 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
- •A: Bloodstream infections
- •a) Suitable for at least 2 antibiotic regimens in the site randomisation list
- •Growth of Gram-negative bacilli identified from blood culture(s)
- •Receiving or planning to receive intravenous antibiotics
- •Expected time from blood culture sampling to randomisation is ≤ 96 hours.
- •B: Ventilator-associated pneumonia / hospital-acquired pneumonia a) Suitable for at least 2 antibiotic regimens in the site randomisation list b) Infection syndrome definitions^( (US Centers for Disease Control and Prevention National Healthcare Safety Network)3: i) At least one of the following:
- •temperature > 38 °C
- •white blood cell count ≥ 12,000 cells/mm3 (12 x 109/L, 12 x 103/µL) or ≤ 4,000 cells/mm3 (4 x 109/L, 4 x 103/µL)
- •altered mental status with no other causes in > 70 years old; AND ii) Two or more chest imaging tests demonstrating at least one of the following:
- •new and progressive OR progressive and persistent infiltrate 2) new and persistent OR progressive and persistent consolidation 3) new and persistent OR progressive and persistent cavitation; AND iii) At least two of the following:
- •new onset of purulent sputum, or change in character of sputum, or increased respiratory secretions, or increased in suctioning requirements
- •new onset or worsening tachypnoea or dyspnoea
- •rales or bronchial breath sounds
- •worsening gas exchange defined by oxygen desaturations (e.g., PaO2/FiO2 < 240), increased oxygen requirements or increased ventilation demand.
- •c) Hospital admission > 48 hours d) Predominant growth of Gram-negative bacilli identified from respiratory tract specimen(s)*; e) Receiving or planning to receive intravenous antibiotics f) Expected time from respiratory culture sampling to randomisation is ≤ 96 hours
- •C: CR-GNB antibiotic backbone domain
- •a) Gram-negative bacilli belonging to Acinetobacter baumannii-calcoaceticus complex, Pseudomonas aeruginosa or Enterobacterales b) Carbapenem resistance in isolate detected - i) Phenotypically via conventional microbiology testing: meropenem / imipenem / ertapenem resistance; OR ii) Genotypically via PCR or next generation sequencing: presence of genes associated with carbapenemase production (eg. blaNDM, blaKPC, blaIMP, blaIMI, blaVIM, blaOXA-48-like).
排除标准
- •Treating team deems enrolment in the study is not in the best interest of the patient
- •Patient is on end-of-life care
- •Patient is incarcerated in a correctional facility
- •Participation in any interventional study activities outlined in the TREAT-GNB study within the last 90 days
- •Pregnant women and children
- •Polymicrobial bloodstream infection
研究组 & 干预措施
Colistin/Polymyxin B + Sulbactam
干预措施: Colistin/Polymyxin B + Sulbactam (Drug)
Colistin/Polymyxin B + Tigecycline/Eravacycline
干预措施: Colistin/Polymyxin B + Tigecycline/Eravacycline (Drug)
Colistin/Polymyxin B + Meropenem
干预措施: Colistin/Polymyxin B + Meropenem (Drug)
Ceftazidime-avibactam + Sulbactam
干预措施: Ceftazidime-avibactam + Sulbactam (Drug)
Ceftazidime-avibactam + Fosfomycin
干预措施: Ceftazidime-avibactam + Fosfomycin (Drug)
Ceftazidime-avibactam
干预措施: Ceftazidime-avibactam (Drug)
Ceftazidime-avibactam + Aztreonam
干预措施: Ceftazidime-avibactam + Aztreonam (Drug)
Ceftazidime-avibactam + Colistin/Polymyxin B
干预措施: Ceftazidime-avibactam + Colistin/Polymyxin B (Drug)
High-dose meropenem
干预措施: High-dose meropenem (Drug)
Meropenem + Fosfomycin
干预措施: Meropenem + Fosfomycin (Drug)
Meropenem-vaborbactam
干预措施: Meropenem-vaborbactam (Drug)
Cefiderocol
干预措施: Cefiderocol (Drug)
Ceftolozane-tazobactam
干预措施: Ceftolozane-tazobactam (Drug)
Ceftolozane-tazobactam + Meropenem
干预措施: Ceftolozane-tazobactam + Meropenem (Drug)
结局指标
主要结局
Clinical outcome
时间窗: 28 days post-randomisation
28-day all-cause mortality after randomisation
次要结局
- Clinical outcome(14, 28 and 90 days post-randomisation)
- Health economics outcomes(28 and 90 days post-randomisation)
研究者
Mo Yin
Consultant / Adjunct Assistant Professor
National University of Singapore