Observational Study on the Efficacy of Empirical Antimicrobial Therapy in Febrile Neutropenia.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Symptom Resolution Rate by Patient-Reported Temperature Diary
研究概览
简要总结
This single-arm, open-label clinical study evaluates the efficacy and safety of a standardized empirical anti-infective escalation protocol for patients with hematological malignancies complicated by febrile neutropenia. The treatment algorithm follows a sequential strategy: initial carbapenem monotherapy (2 days) → if ineffective, combination with vancomycin/linezolid (3 days) → if no response, escalation to antifungal therapy (7 days). For patients demonstrating persistent or recurrent fever with uncontrolled infection parameters after 12-14 days of prior empirical anti-infective therapy, switching to ceftazidime-avibactam combined with aztreonam is implemented. Therapeutic efficacy is assessed through comprehensive evaluation of clinical manifestations, inflammatory biomarkers, radiographic imaging, and microbiological findings. Comprehensive safety surveillance includes continuous monitoring of adverse events and all-cause mortality throughout the treatment course.
详细描述
This study is a single-arm, open-label, observational clinical investigation focusing on patients with hematological malignancies complicated by febrile neutropenia. It aims to evaluate the overall efficacy and safety of a standardized empirical anti-infective treatment algorithm. The protocol employs a unified step-up therapeutic strategy: initial empirical administration of a carbapenem antibiotic (for 2 days); if ineffective, combination with an anti-Gram-positive agent (e.g., vancomycin or linezolid) (for 3 days); if there is still no response, initiation of antifungal therapy (for 7 days); For patients exhibiting persistent or recurrent fever with uncontrolled infection-related parameters after 12-14 days of prior empirical anti-infective therapy, an empirical multidrug-resistant regimen consisting of ceftazidime-avibactam combined with aztreonam is considered. The treatment duration will be adjusted based on neutrophil recovery and febrile status. The study will assess overall efficacy through a comprehensive evaluation of clinical symptoms and signs, inflammatory biomarkers (e.g., C-reactive protein, procalcitonin), radiographic findings, and microbiological results. Safety monitoring will include continuous surveillance of adverse events (AEs) and all-cause mortality throughout the treatment course.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75 years.
- •Documented haematological malignancy: acute leukaemia, severe aplastic anaemia, lymphoma, or multiple myeloma.
- •Neutropenia: absolute neutrophil count (ANC) < 0.5 × 10⁹/L, or ANC anticipated to fall below this threshold within 48 h; severe neutropenia defined as ANC < 0.1 × 10⁹/L.
- •Fever: single oral temperature ≥ 38.3 °C (axillary ≥ 38.0 °C), or oral temperature ≥ 38.0 °C (axillary ≥ 37.7 °C) sustained for > 1 h.
- •Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-
- •Planned or current empirical use of ceftazidime-avibactam (CAZ-AVI) for febrile neutropenia.
排除标准
- •Drug-related fever or fever attributable to rheumatic/autoimmune disease.
- •Concomitant intracranial haemorrhage.
- •Pregnancy, lactation, or intention to become pregnant.
- •Psychiatric disorder or any condition precluding protocol compliance.
- •Life-threatening arrhythmia or QTc > 500 ms on electrocardiography.
结局指标
主要结局
Symptom Resolution Rate by Patient-Reported Temperature Diary
时间窗: two days
Proportion of patients achieving defervescence (oral temperature \< 38 °C sustained for ≥ 8 h) AND absence of infection-related symptoms recorded in a validated patient diary within 48 h after starting empirical therapy.
C-Reactive Protein Serum Concentration Change (mg/L)
时间窗: two days
Absolute decrease from baseline in high-sensitivity CRP measured by immunoturbidimetric assay at 48 h.
Procalcitonin Plasma Concentration Change (ng/mL)
时间窗: Two days
Absolute decrease from baseline in PCT measured by electrochemiluminescence immunoassay at 48 h.
Pulmonary Infiltrate Resolution on CT or Chest X-ray
时间窗: Two weeks
Proportion of patients with ≥ 50 % reduction in the longest diameter of any lung infiltrate compared with baseline scan.
Pathogen Positivity Rate in Blood or Sterile-Site Cultures
时间窗: one week
Cumulative proportion of patients with clinically relevant bacteria or fungi isolated from blood or other normally sterile sites processed by automated BACTEC™ culture system.
Physical Sign Resolution Score by Clinician Examination
时间窗: two days
Proportion of patients in whom predefined signs (erythema, tenderness, exudate, etc.) disappear or improve by ≥ 50 % on a 4-point clinician-graded scale.
次要结局
- First-Line Carbapenem Clinical Success Rate(three days)
- Carbapenem Plus Anti-Gram-Positive Agent Clinical Success Rate(three days)
- Antifungal Therapy Biomarker Response Rate(three days)
- CRE/MDR-GNB Eradication Rate After CAZ-AVI Plus Aztreonam(three days)
- Incidence of Adverse Events Assessed by CTCAE v5.0 (Entire Course)(From first antimicrobial dose to 30 days post-therapy)
- All-Cause Mortality Rate(30 days)