Appropriate Management of Bacteriemic Febrile Neutropenia in High-Risk Hematological Patients. Relationship Between Duration of Antibiotic Administration, Outcome and Resistance Profile
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 172
- 试验地点
- 1
- 主要终点
- Days Free from Anti-Gram-Negative Antibiotic Therapy within 28 days
研究概览
简要总结
The goal of this clinical trial is to learn if a personalized duration of antibiotic therapy, based on clinical stability, is as effective as a standard duration of at least 10 days in hospitalized patients with hematologic malignancies (such as leukemia or lymphoma) who develop febrile neutropenia and Gram-negative bacteraemia.
The main questions it aims to answer are:
- Can a personalized antibiotic duration increase the number of days free from anti-Gram-negative therapy within 28 days without compromising patient safety?
- How does the duration of antibiotic therapy (short vs. prolonged) affect the rate and modality of gut microbiota reconstitution?
Researchers will compare:
- Group A (Personalized Duration): Antibiotics are stopped after the patient maintains clinical stability (no fever and stable vital signs) for 72 consecutive hours.
- Group B (Standard of Care): Antibiotics are continued for a standard duration, typically at least 10 days, based on current clinical surveys and physician decision.
Participants will:
- Be randomized to receive either the personalized or the standard duration of antibiotic therapy once a Gram-negative infection is confirmed in the blood.
- Be monitored for 28 days to assess for new fever episodes, recurrence of infection, and overall survival.
- If participating in the microbiological sub-study, provide biological samples (blood, feces, and rectal swabs) at specific time points (at the onset of fever, at the end of treatment, and at day 28).
- Undergo specialized laboratory testing (Whole Metagenomic Sequencing) on the collected samples to evaluate the evolution of their intestinal and blood microbiota and the presence of antibiotic-resistant genes.
详细描述
This is a multicenter, open-label, randomized controlled trial. Upon confirmation of Gram-negative bacteraemia, eligible patients are randomized 1:1 to one of two treatment strategies:
- Experimental Arm (Personalized Duration): Antibiotic therapy is discontinued once the patient achieves and maintains clinical stability for 72 consecutive hours. Clinical stability is defined as apyrexia (Tc < 38°C) for at least 48 hours and a stable or improving qSOFA score.
- Control Arm (Standard of Care): Antibiotic therapy duration follows local clinical practice, with a suggested minimum duration of 10 days, consistent with current European and Asian hematological guidelines.
In parallel, a prospective observational microbiological sub-study will utilize Shotgun Metagenomic Next-Generation Sequencing (mNGS) to analyze the evolution of the intestinal and blood microbiota. The goal is to compare the rate of MDR organism colonization and the reconstitution of the healthy microbiome between the two antibiotic duration strategies.
All participants will undergo clinical monitoring until day 28. For those enrolled in the sub-study, biological samples (stool, rectal swabs, and blood) will be collected at baseline (V1), at the end of treatment (V4), and at the end of the study (V5). These samples will be analyzed to identify clinically significant bacteria and antibiotic-resistance genes.
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
- •Diagnosed with a hematologic malignancy that is candidate for treatment with chemotherapy or bone marrow transplantation or chimeric antigen receptor T cell therapy (CAR-T)
- •Diagnosis of febrile neutropenia defined according to the guidelines of the Infectious Disease Society of America, IDSA; ref: Freifeld, A.G., et al., Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis,
- •52(4): p. e56-93.) as: Fever: single record of oral temperature >=38.3°C or a temperature >=38.0°C sustained over a period of one hour; Neutropenia: absolute neutrophil count < 1000 cells/microL; Expected duration of neutropenia >= 7 days
- •Diagnosis of bacteraemia defined by positive blood cultures (at least 1 vial positive for a non-contaminating microorganism)
- •Isolation of Gram-Negative species
排除标准
- •Contextual diagnosis of pneumonia
- •Contextual diagnosis of intra-abdominal infection, in particular: neutropenic enterocolitis/typhlitis or biliary tract infection
- •Persistently positive blood cultures at randomization
- •Any condition that endangers the safety of the patient based on the judgment of the treating physician
研究组 & 干预措施
Standard of Care
Standard of care antibiotic therapy with a suggested minimum duration of 10 days.
干预措施: Standard of Care Antibiotic Duration (Other)
Personalized Duration
Patients in this arm will receive antibiotic therapy for a duration guided by clinical stability. Antibiotics will be discontinued after 72 consecutive hours of clinical stability, defined as apyrexia (Tc < 38°C) for at least 48 hours and stable or improved qSOFA score.
干预措施: Clinical Stability-Driven Antibiotic Discontinuation Strategy (Other)
结局指标
主要结局
Days Free from Anti-Gram-Negative Antibiotic Therapy within 28 days
时间窗: From the date of index blood culture collection (Day 0) up to Day 28
Number of days that the participant is alive and free from any anti-Gram-negative antibiotic therapy, calculated from the date of the index blood culture collection (onset of infection) up to Day 28. Antibiotics active exclusively on Gram-positive bacteria (e.g., glycopeptides, daptomycin) and fluoroquinolone prophylaxis are excluded from this calculation.
次要结局
- Incidence of New Fever Episodes(From the end of antibiotic therapy up to Day 28)
- 28-day All-cause Mortality(Up to Day 28)
- Relapse of Bloodstream Infection (BSI) by the Same Pathogen(From the end of antibiotic therapy up to Day 28)
- Recurrent BSI by Gram-negative Bacteria(From the end of antibiotic therapy up to Day 28)
- Emergence of Multi-Drug Resistant Organisms (MDRO)(Within 90 days from the index blood culture collection)
- Incidence of Clostridioides difficile Infection (CDI)(Up to Day 28)
- Incidence of Antibiotic-Related Adverse Events(Up to Day 28)
研究者
Valeria Cento
Associate Professor of Microbiology
Humanitas University