Ceftolozane/Tazobactam Versus Meropenem for Febrile Neutropenia on Patients Colonized With or at Risk for Infection With Extended Spectrum Beta Lactamase (ESBL)-Producing Pathogens: a Randomized Double-blind Non-inferiority Trial.
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 176
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Intent-to-Treat (ITT) Population
研究概览
简要总结
The study proposes a planned, double-blind, non-inferiority clinical trial involving patients with febrile neutropenia and risk of extended-spectrum beta-lactamase (ESBL) infection. The goal is:
- Analyze the efficacy and tolerability of Ceftolozane/tazobactam (CEF/TAZ) compared to the current standard of care (meropenem) in patients with febrile neutropenia and risk of ESBL infection.
Patients will be randomly assigned to receive CEF/TAZ or meropenem, with assessment of clinical response, toxicity and microbiological evolution. Stool samples will be collected before, during and after treatment for intestinal microbiota analysis and intestinal microbiome analysis to evaluate possible effects on GVHD. Analysis of the results will include the taxonomic classification of the organisms present. Data will be analyzed to assess non-inferiority in clinical response, incidence of GVHD, antimicrobial resistance and other outcomes.
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
- Quadruple (Participant, Care Provider, Investigator, 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
- 未提供
排除标准
- •Patients known to be colonized with carbapenem-resistant or CEF/TAZ-resistant pathogens
- •Patients with previous use of carbapenems for at least 48h in the past 30 days are also excluded due to risk of resistance to the study drugs.
- •Growth of a pathogen resistant to either study drug in a relevant clinical specimen during the intervention phase will be followed by adjustment of therapy according to local protocol, unblinding, and exclusion from the study.
- •Patients that have received less than 72h of either study drug will also be excluded from the final analyses.
研究组 & 干预措施
Intervention
In the intervention arm 3g of ceftolozane-tazobactam are given intravenously every 8 hours. Duration of therapy should follow local guidelines and de-escalation is allowed after identification of causative pathogens.
Colonized patients will be considered those identified through positive routine rectal swabs and/or positive culture of a clinical sample) or at risk of infection by an ESBL-producing pathogen due to use of 3rd/4th gen cephalosporin or piperacillin/tazobactam for at least 48 hours. in the last 30 days.
干预措施: Ceftolozane-Tazobactam (Drug)
Control
The comparator arm consists of 2g of meropenem given intravenously every 8 hours.Duration of therapy should follow local guidelines and de-escalation is allowed after identification of causative pathogens.
Colonized patients will be considered those identified through positive routine rectal swabs and/or positive culture of a clinical sample) or at risk of infection by an ESBL-producing pathogen due to use of 3rd/4th gen cephalosporin or piperacillin/tazobactam for at least 48 hours. in the last 30 days.
干预措施: Meropenem (Drug)
结局指标
主要结局
Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Intent-to-Treat (ITT) Population
时间窗: Within 24 hours after last dose of study drug (Up to ~Day 15)
To compare the clinical response rates at the EOT visit for ceftolozane/tazobactam versus meropenem. Clinical response at the EOT visit was defined as cure (complete resolution of fever and symptoms related to Febrile Neutropenia episode), failure (non-resolution, relapse or recurrence of Febrile Neutropenia) or indeterminate (no evaluable study data). A favorable clinical response is a clinical cure. A missing clinical response will be considered indeterminate.
次要结局
- Percentage of Participants With Clinical Response of Clinical Cure at the End-of-Therapy (EOT) Visit in the Microbiological Intent-to-Treat (mITT) Population(7 to 14 days after last dose of study drug (Up to ~Day 30))
- Frequency of multidrug resistant-pathogen infections or colonization(Until100 days after allogenic HSCT)
- Percentage of Participants With Clinical Response of Clinical Cure at the Test-of-Cure (TOC) Visit in the Intent-to-Treat (ITT) Population(7 to 14 days after last dose of study drug (Up to ~Day 30))
- Incidence of microbiologically documented infections and identification of causative organisms in culture(Up to 100 days)
- Percentage of Participants Who Report 1 or More Adverse Event (AE)(Up to 35 days after last dose of study drug)
- Percentage of Participants With Any Serious Adverse Event (SAE)(Up to 35 days after last dose of study drug (Up to ~Day 50) ])
- In-hospital mortality(Until100 days after allogenic HSCT)
- Occurrence of graft versus host disease (GVHD)(Until100 days after allogenic HSCT)
- Faecal microbiota analysis(Up to 100 days)
- Percentage of Participants Discontinuing Study Drug Due to an Adverse Event (AE)(Up to 14 days after the first dose of study drug (Up to ~Day 15))
研究者
João Antonio Gonçalves Garreta Prats
Principal Investigator
Beneficência Portuguesa de São Paulo