Ceftazidime Plus Fosfomycin Versus Ceftazidime Alone for Severe Gram-negative Infections: a Triple-blind, Placebo-controlled Point-of-care Randomized Clinical Trial
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Time in hours from first study-medication administration to normalization of all qSOFA parameters and decrease of peak CRP by 50%.
研究概览
简要总结
The goal of this clinical trial is to :
- Test whether the combination of CAZ±AVI and FOS leads to superior clinical outcomes in patients with severe suspected Gram-negative bacterial infection, as demonstrated by a shorter time to normalization of quick Sequential Organ Failure Assessment (qSOFA) parameters and reduction in C-reactive protein (CRP) compared to standard of care (CAZ±AVI alone)
- to further characterize the safety profile of this combination therapy
In the presence of such an infection, standard treatment is to start intravenous antibiotic therapy. Ceftazidime (Fortam®), or ceftazidime-avibactam (Zavicefta®), is a standard antibiotic commonly used for this purpose (for very resistant bacteria, the compound avibactam is included to protect ceftazidime from being broken down by bacteria).
Researchers will compare ceftazidime (or ceftazdime-avibactam) plus fosfomycin versus ceftazidime alone with placebo (i.e. a look-alike substance given with no drug) to examine whether the addition of another intravenous antibiotic, fosfomycin, would lead to faster recovery from severe infection and evaluate the tolerability of this combination.
Participants will:
- Be randomly assigned to either the intervention group or the control group.
- The intervention group will receive ceftazidime (with avibactam if multidrug resistant bacteria are suspected, per routine practice) and intravenous fosfomycin, and the control group will receive ceftazidime (with avibactam if multidrug resistant bacteria are suspected) and placebo.
- Either treatment will be given for 3 days, three times daily (or less frequently, depending on renal function).
- Provide a few extra blood samples (for CRP measurement, a protein marker of inflammation) during the first few days of the study.
- Be contacted in the hospital or by phone if discharged on day 28 to be asked a few questions.
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
- •Adult (≥18 years)
- •Hospitalized with suspected severe Gram-negative bacterial infection
- •Signed informed consent from the patient (or oral consent from a patient with capacity but with physical inability to sign, with signed witness testimony from a person independent of the study team) of from the legal representative if the patient lacks capacity to provide informed consent
排除标准
- •Pregnancy or lactation
- •Known contra-indication to CAZ±AVI or FOS
- •Gram-negative directed antibiotic treatment begun >24 hours before inclusion
研究组 & 干预措施
Ceftazidime± avibactam with fosfomycin (CAZ±AVI+ FOS)
The experimental intervention is a combination of CAZ with FOS, brand name InfectoFos®, each vial containing 2 g of fosfomycin, and 2.64 g fosfomycin disodium.
干预措施: Ceftazidime± avibactam with fosfomycin (Drug)
Ceftazidime± avibactam with placebo (CAZ±AVI + placebo)
Control arm will be CAZ±AVI combined with placebo.
干预措施: Ceftazidime± avibactam with placebo (Drug)
结局指标
主要结局
Time in hours from first study-medication administration to normalization of all qSOFA parameters and decrease of peak CRP by 50%.
时间窗: From date of randomization until the date of first documented normalization of qSOFA and 50% decrease in CRP. We estimate median time to be of approximately 108h and 96h in the control and intervention groups, respectively (approx 4 to 5 days)
qSOFA scores will be collected as per routine ward practices and at minimum every 2 hours for patients with abnormal scores, until normalization. CRP will be measured twice daily (12 ± 4 hours apart), for 6 days or until the 50% reduction from peak is observed, whichever occurs earlier. Thereafter, measurements will be taken as clinically indicated.
次要结局
- Incidence of adverse events of special interest (AESI)(From day 1 to day 3 (+/-1 day) of intervention and up to 48h after the last administration of the study medication/placebo)
研究者
Angela HUTTNER
Professor, Attending physician, Division of Infectious Diseases
University of Geneva, Switzerland