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

NCT07204522 | Recruiting

• 1 other identifier: ShanxiBethuneH3
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Febrile Neutropenia

Outcome Measures

Primary Outcomes (6)

• Symptom Resolution Rate by Patient-Reported Temperature Diary

  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.

  two days

• C-Reactive Protein Serum Concentration Change (mg/L)

  Absolute decrease from baseline in high-sensitivity CRP measured by immunoturbidimetric assay at 48 h.

  two days

• Procalcitonin Plasma Concentration Change (ng/mL)

  Absolute decrease from baseline in PCT measured by electrochemiluminescence immunoassay at 48 h.

  Two days

• Pulmonary Infiltrate Resolution on CT or Chest X-ray

  Proportion of patients with ≥ 50 % reduction in the longest diameter of any lung infiltrate compared with baseline scan.

  Two weeks

• Pathogen Positivity Rate in Blood or Sterile-Site Cultures

  Cumulative proportion of patients with clinically relevant bacteria or fungi isolated from blood or other normally sterile sites processed by automated BACTEC™ culture system.

  one week

• Physical Sign Resolution Score by Clinician Examination

  Proportion of patients in whom predefined signs (erythema, tenderness, exudate, etc.) disappear or improve by ≥ 50 % on a 4-point clinician-graded scale.

  two days

Secondary Outcomes (6)

• 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

Interventions

Carbapenems DRUG

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

Anti-Gram-positive agent DRUG

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.

Antifungal agent DRUG

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.

Ceftazidime-avibactam + Aztreonam DRUG

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-avibactam plus aztreonam to cover multidrug-resistant pathogens, while concurrently maintaining antifungal treatment. This escalation strategy is indicated for febrile neutropenic patients with underlying hematologic malignancies.

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This single-arm, open-label, observational study will enrol adult patients with haematological malignancies who develop febrile neutropenia and are scheduled to receive empirical ceftazidime-avibactam. Eligible participants are aged 18-75 years with acute leukaemia, severe aplastic anaemia, lymphoma or multiple myeloma, an absolute neutrophil count \< 0.5 × 10⁹/L (or expected to fall below this within 48 h), fever ≥ 38.3 °C, ECOG performance status 0-2, and no contraindications such as drug fever, intracranial haemorrhage, pregnancy, or QTc \> 500 ms. The cohort will reflect the real-world haematology ward population at high risk for multidrug-resistant Gram-negative infections.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shanxi Bethune Hospital: lead

Study Sites (1)

Shanxi Bethune Hospital

Taiyuan, Shanxi, 030000, China

RECRUITING

MeSH Terms

Conditions

Febrile Neutropenia

Interventions

Carbapenems; Antifungal Agents; avibactam, ceftazidime drug combination; Aztreonam

Condition Hierarchy (Ancestors)

Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Monobactams; Sulfur Compounds; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: October 2, 2025
• Study Start: September 22, 2025
• Primary Completion (Estimated): September 22, 2027
• Study Completion (Estimated): September 22, 2027
• Last Updated: October 2, 2025

Record last verified: 2025-09

Locations

CN (1)