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

Recruiting

• Conditions: Febrile Neutropenia

• Registration Number: NCT07204522
• Lead Sponsor: Shanxi Bethune Hospital

Brief Summary

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.

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-15
• Study Start: 2025-09-22
• Study First Submitted QC: 2025-09-24
• Last Update Submitted: 2025-09-24
• Study First Posted: 2025-10-02
• Last Update Posted: 2025-10-02
• Primary Completion: 2027-09-22
• Study Completion: 2027-09-22

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Symptom Resolution Rate by Patient-Reported Temperature Diary	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)	two days	Absolute decrease from baseline in high-sensitivity CRP measured by immunoturbidimetric assay at 48 h.
Procalcitonin Plasma Concentration Change (ng/mL)	Two days	Absolute decrease from baseline in PCT measured by electrochemiluminescence immunoassay at 48 h.
Pulmonary Infiltrate Resolution on CT or Chest X-ray	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	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	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.

Secondary Outcome Measures

Name	Time	Method
First-Line Carbapenem Clinical Success Rate	three days	Proportion achieving defervescence AND ≥ 50 % CRP decrease at 72 h on carbapenem monotherapy.
Carbapenem Plus Anti-Gram-Positive Agent Clinical Success Rate	three days	Proportion achieving defervescence AND ≥ 50 % CRP decrease at 72 h after adding vancomycin or linezolid.
Antifungal Therapy Biomarker Response Rate	three days	Proportion with ≥ 50 % reduction in serum galactomannan (Platelia™ ELISA) or β-D-glucan (Fungitell™) at 72 h post-antifungal initiation.
CRE/MDR-GNB Eradication Rate After CAZ-AVI Plus Aztreonam	three days	Proportion of patients with documented CRE/MDR-GNB whose follow-up blood or sterile-site culture becomes negative within 72 h of starting ceftazidime-avibactam plus aztreonam.
Incidence of Adverse Events Assessed by CTCAE v5.0 (Entire Course)	From first antimicrobial dose to 30 days post-therapy	Number and grade of drug-related cardiac, hepatic, renal, or allergic adverse events captured through CTCAE v5.0 forms.
All-Cause Mortality Rate	30 days	Proportion of participants who die from any cause within 30 days after enrolment.

Trial Locations

Locations (1)

Shanxi Bethune Hospital; 🇨🇳 Taiyuan, Shanxi, China