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NCT Number: NCT07204522

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

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.

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Key information

Conditions

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

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Shanxi Bethune Hospital

Taiyuan, Shanxi, 030000, China

Location status: Recruiting

Location contact

Tao Wang, Dr.

CONTACT

[email protected]

13835175119

About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Primary outcomes

  1. Symptom Resolution Rate by Patient-Reported Temperature Diary

    Time frame: 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.

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

    Time frame: two days

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

  3. Procalcitonin Plasma Concentration Change (ng/mL)

    Time frame: Two days

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

  4. Pulmonary Infiltrate Resolution on CT or Chest X-ray

    Time frame: Two weeks

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

  5. Pathogen Positivity Rate in Blood or Sterile-Site Cultures

    Time frame: 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.

  6. Physical Sign Resolution Score by Clinician Examination

    Time frame: 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 outcomes

  1. First-Line Carbapenem Clinical Success Rate

    Time frame: three days

    Proportion achieving defervescence AND ≥ 50 % CRP decrease at 72 h on carbapenem monotherapy.

  2. Carbapenem Plus Anti-Gram-Positive Agent Clinical Success Rate

    Time frame: three days

    Proportion achieving defervescence AND ≥ 50 % CRP decrease at 72 h after adding vancomycin or linezolid.

  3. Antifungal Therapy Biomarker Response Rate

    Time frame: three days

    Proportion with ≥ 50 % reduction in serum galactomannan (Platelia™ ELISA) or β-D-glucan (Fungitell™) at 72 h post-antifungal initiation.

  4. CRE/MDR-GNB Eradication Rate After CAZ-AVI Plus Aztreonam

    Time frame: 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.

  5. Incidence of Adverse Events Assessed by CTCAE v5.0 (Entire Course)

    Time frame: 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.

  6. All-Cause Mortality Rate

    Time frame: 30 days

    Proportion of participants who die from any cause within 30 days after enrolment.

Sponsors and collaborators

Lead sponsor

Shanxi Bethune Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Oct 2, 2025
Registry last updated
Oct 2, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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