Efficacy of Empirical Anti-Infective Therapy in Neutropenic Febrile Patients.

Официальное название

Observational Study on the Efficacy of Empirical Antimicrobial Therapy in Febrile Neutropenia.

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Carbapenems
  First-line empirical agent for febrile neutropenia complicating hematologic malignancies: carbapenem.
• Препарат Anti-Gram-positive agent
  Escalation to a carbapenem plus an anti-Gram-positive agent (vancomycin or linezolid) is instituted if no defervescence occurs after 48h of first-line therapy; this combination is maintained for 3 days before further escalation in febrile-neutropenia patients with underlying hematologic malignancies.
• Препарат Antifungal agent
  If combination therapy with a carbapenem plus an anti-Gram-positive agent (vancomycin or linezolid) remains ineffective after 72 h, empirical antifungal coverage is added while continuing antibacterial therapy for an additional 7 days; failure to defervesce thereafter mandates further therapeutic escalation in febrile-neutropenic patients with hematologic malignancies.
• Препарат Ceftazidime-avibactam + Aztreonam
  If the combination of a carbapenem and an anti-Gram-positive agent (vancomycin or linezolid) fails to achieve defervescence after 3 days of treatment, an antifungal agent is added while continuing the original antibacterial regimen for an additional 7 days. Should fever persist or recur with uncontrolled infection-related parameters after 12-14 days of empirical anti-infective therapy, the carbapenem/anti-Gram-positive combination is discontinued. Therapy is then switched to ceftazidime-avibacta

Первичные конечные точки

• Symptom Resolution Rate by Patient-Reported Temperature Diary [Срок оценки: two days]
• C-Reactive Protein Serum Concentration Change (mg/L) [Срок оценки: two days]
• Procalcitonin Plasma Concentration Change (ng/mL) [Срок оценки: Two days]
• Pulmonary Infiltrate Resolution on CT or Chest X-ray [Срок оценки: Two weeks]
• Pathogen Positivity Rate in Blood or Sterile-Site Cultures [Срок оценки: one week]
• Physical Sign Resolution Score by Clinician Examination [Срок оценки: two days]

Вторичные конечные точки (6)

• First-Line Carbapenem Clinical Success Rate [Срок оценки: three days]
• Carbapenem Plus Anti-Gram-Positive Agent Clinical Success Rate [Срок оценки: three days]
• Antifungal Therapy Biomarker Response Rate [Срок оценки: three days]
• CRE/MDR-GNB Eradication Rate After CAZ-AVI Plus Aztreonam [Срок оценки: three days]
• Incidence of Adverse Events Assessed by CTCAE v5.0 (Entire Course) [Срок оценки: From first antimicrobial dose to 30 days post-therapy]
• All-Cause Mortality Rate [Срок оценки: 30 days]

Критерии участия

Критерии включения

• 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) 0-2.
• Planned or current empirical use of ceftazidime-avibactam (CAZ-AVI) for febrile neutropenia.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• Shanxi Bethune Hospital — Taiyuan

Идентификаторы

NCT: NCT07204522 · ShanxiBethuneH3

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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