Ceftazidime-Avibactam Versus Colistin in Critically Ill Patients With Carbapenem-Resistant Enterobacteriaceae Infections (AVI-ICU): A Non-Inferiority Randomized Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- 28-day mortality
研究概览
简要总结
Carbapenem-Resistant Enterobacteriaceae (CRE) infections are a growing national and international challenge in healthcare settings. This is not only due to the rapid spread of resistance and paucity of options of targeted-antimicrobial agents, but also owing to the high mortality of patients infected with CRE reaching up to 50% as per the Centers of Disease Control and Prevention.
Colistin-based combination regimens have been the mainstay for treating CRE-related infections. Ceftazidime-avibactam is a beta-lactamase inhibitor combination, a novel antibiotic, which recently showed a better clinical and microbiological cure against CRE along with the potential to reduce mortality and nephrotoxicity in comparison to colistin-based regimens in observational studies. However, randomized clinical trials are lacking.
This non-inferiority randomized controlled study aims to assess the efficacy and safety of ceftazidime-avibactam-based regimens in critically ill patients with CRE infections in comparison to colistin-based regimens.
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 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged ≥ 18 years.
- •Admitted to an intensive care unit (ICU).
- •Patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP), complicated urinary tract infection (cUTI), bacteremia, complicated intraabdominal infection (cIAI), and complicated skin and soft tissue infection (cSSTI).
- •Confirmed infection with CRE, based on a culture and sensitivity obtained within the past 72 hours of study enrollment.
- •Suspected CRE infection according to one of the following: (1) positive Xpert Carba-R test screening for blaKPC or blaOXA-48 or blaNDM or blaVIM or blaIMI assessed on the admission to the ICU, (2) positive culture for CRE obtained within 3 months from time of enrollment.
排除标准
- •Acute Physiology and Chronic Health Evaluation II (APACHE II) score more than 30
- •known significant hypersensitivity reaction to beta-lactam antibiotics or colistin
- •Positive culture for Stenotrophomonas maltophilia or Acinetobacter baumannii within the current hospitalization.
- •Patients received the study intervention or control for more than 24 hours before the intended randomization.
- •Patient/substitute decision-maker or caring physician's refusal to enroll in the study.
- •Patient with concomitant suspected or confirmed meningitis.
- •Cystic fibrosis.
- •Patients with Do Not Attempt to Resuscitate (DNAR) code status.
- •Prior knowledge that the index CRE pathogen was resistant to colistin (MIC >2 μg/ml) or ceftazidime-avibactam (MIC > 8 μg/ml) before randomization.
- •Objective clinical evidence for any of the following infections that necessitate study therapy for >14 days: endovascular infection, including endocarditis, osteomyelitis, prosthetic joint infection, meningitis, and/or other central nervous system infections
研究组 & 干预措施
Ceftazidime-avibactam
Ceftazidime-avibactam 2.5 grams intravenous (IV) every 8 hours infused over two hours for a duration of 7-14 days, with dose adjustment for renal impairment according to the FDA prescribing information. Patients who have a positive Xpert Carb-R screening test or culture for CRE with metallo-beta-lactamases will receive aztreonam added to ceftazidime-avibactam.
干预措施: Ceftazidime-avibactam (Drug)
Colistin
Colistin (9-million-unit loading dose IV followed with 9 million units IV daily divided into 3 doses), for 7 to 14 days. Patients with renal impairment will receive antibiotics with adjusted doses based on their glomerular filtration rate or the use and type of renal replacement therapy according to the 2019 International Consensus Guidelines for the Optimal Use of the Polymyxins.
干预措施: Colistin (Drug)
结局指标
主要结局
28-day mortality
时间窗: 28 days from randomization
Death
次要结局
- Time to weaning from mechanical ventilation at day 28(28 days from randomization)
- 14-day mortality(14 days from randomization)
- Number of patients with microbiological response at the EOT at days 7-14 from randomization and TOC 7 days after completion of treatment(EOT at 7-14 days from randomization and TOC 7 days after completion of treatment)
- Number of patients with clinical success at end of therapy (EOT) at day 7-14 from randomization and test of cure (TOC) 7 days after completion of treatment(EOT at 7-14 days from randomization and TOC 7 days after completion of treatment)
- Drug-related adverse events(28 days from randomization)
- Requirement for renal replacement therapy at day 28(28 days from randomization)
- Intensive care unit (ICU) length of stay, censored at 28 days(28 days from randomization)
- Days alive and out of the ICU, censored at 28 days(28 days from randomization)
研究者
Zainab Alduhailib
Critical Care Medicine Consultant
King Faisal Specialist Hospital & Research Center