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

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Drug Carbapenems
  First-line empirical agent for febrile neutropenia complicating hematologic malignancies: carbapenem.
• Drug 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.
• Drug 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.
• Drug 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

Primary outcome measures

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

Secondary outcome measures (6)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model

Cohort

Study locations

China · 1 center

• Shanxi Bethune Hospital — Taiyuan

Identifiers

NCT: NCT07204522 · ShanxiBethuneH3

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗