Early Neutropenic Fever De-escalation (END) of Antibiotics Study
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 260
- 主要终点
- Antibiotic utilization
研究概览
简要总结
This is a randomized, open label clinical trial among individuals with hematologic conditions. The trial aims to evaluate the safety and clinical outcomes of de-escalating antibiotic therapy among stable individuals diagnosed with neutropenic fever, in which no bacterial infection has been identified.
详细描述
Background:
The Infectious Disease Society of America (IDSA) guidelines for febrile neutropenia conflict with several other international guidelines on duration of antibiotic therapy in patients with febrile neutropenia without a documented infectious source. The IDSA recommends continuing antibiotic therapy until clear signs of marrow recovery, while other guidelines, including the European guidelines, allow for earlier discontinuation if no source of bacterial infection is identified. Benefits of earlier discontinuation of antibiotics include mitigating the risk of induction and amplification of antibiotic resistance, decreased disruption of the microbiome, as well as minimizing potential side effects and complications associated with long-term antibiotic use. To date the only randomized clinical trial in adults evaluating an abridged course of antibiotic therapy in high-risk patients with febrile neutropenia (defined as neutropenia for at least 7 days) was a superiority study that demonstrated fewer days of antibiotic use in the control arm. Safety data were a secondary outcome. Further research is needed to assess the safety and clinical outcomes of targeted antibiotic therapy for patients with febrile neutropenia.
Study Design:
This is a randomized, open label clinical trial among individuals with hematologic conditions. The trial aims to evaluate the safety and clinical outcomes of de-escalating antibiotic therapy among stable individuals diagnosed with neutropenic fever, in which no bacterial infection has been identified.
Treatment Regimen:
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
- 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
- •Participant or healthcare proxy with the ability to understand and willingness to sign an informed consent.
- •Adults >18 years old.
- •Likely to have neutropenia > 7 days including such conditions as: acute leukemia; lymphoproliferative disease; multiple myeloma; myelodysplastic syndrome; bone marrow aplasia and autologous or allogeneic hematopoietic stem cell transplantation. Neutropenia defined as absolute neutrophil count <
- •Received or planned to receive cytotoxic chemotherapy. No restrictions on prior therapy regarding dose or agent.
- •High-risk neutropenia defined as expected duration of absolute neutrophil count less than 500 cells/µL for seven or more days.
- •Admitted as an inpatient at Mass General Brigham or Dana Farber Cancer Institute (DFCI).
- •Initial fever (defined as a single oral temperature of ≥38.3°C or a temperature of ≥38.0°C sustained over a one-hour period) during hospital admission or as reason for admission.
- •Has been afebrile for 48 hours.
排除标准
- •Microbiologically or clinically suspected bacterial infection after index fever.
- •Exposure to treatment antibacterial therapy 72 hours before first fever occurrence other than antibiotics deemed as prophylaxis.
研究组 & 干预措施
Intervention Arm
Participants will stop empiric antibiotic therapy after their episode of fever if afebrile for 48 hours, no clinically documented source of bacterial infection, and no hemodynamic or respiratory decompensation.
干预措施: Cessation of antibiotics (Drug)
结局指标
主要结局
Antibiotic utilization
时间窗: 60 days
To compare the days of antibiotic spectrum coverage (DASC), in each arm between randomization and count recovery.
Mortality, transfer to the ICU, septic shock, culture-confirmed bacteremia
时间窗: 60 days
To compare number of patients with a 60-day composite of mortality, transfer to the ICU, septic shock, culture-confirmed bacteremia in each arm.
次要结局
- Adverse Events(60 days)
- Length of stay(60 days)
- Allergic Reactions(60 days)
- Mortality post F&N(60 days)
- Bacteremia(60 days)
- Drug resistance(60 days)
- Candidiasis(60 days)
- Neutropenia(60 days)
- Readmissions(60 days)
- Clostridium difficile infection(60 days)
- Fever(60 days)
研究者
Lindsey R. Baden, MD
Professor of Medicine
Brigham and Women's Hospital