Febrile NeutropeniaNCT07204522
Efficacy of Empirical Anti-Infective Therapy in Neutropenic Febrile Patients.
An observational study of Febrile Neutropenia, run by Shanxi Bethune Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Febrile Neutropenia
- What is being tested?
- Carbapenems, Anti-Gram-positive agent and Antifungal agent
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 22 Sep 2025to 22 Sep 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shanxi Bethune Hospital
Taiyuan, Shanxi, 030000
Tao Wang, Dr., 13835175119, wangtao99699@163.com
About this study
Official title: Observational Study on the Efficacy of Empirical Antimicrobial Therapy in Febrile Neutropenia.
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.
Read the 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.
- Conditions
- Febrile Neutropenia
- Being tested
- Carbapenems, Anti-Gram-positive agent, Antifungal agent, Ceftazidime-avibactam + Aztreonam
- Medical subject headings
- Febrile Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarbapenemsDrug
First-line empirical agent for febrile neutropenia complicating hematologic malignancies: carbapenem.
Anti-Gram-positive agentDrug
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 agentDrug
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 + AztreonamDrug
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: two days
Procalcitonin Plasma Concentration Change (ng/mL)
Absolute decrease from baseline in PCT measured by electrochemiluminescence immunoassay at 48 h.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: two days
Secondary outcomes (6)
First-Line Carbapenem Clinical Success Rate
Proportion achieving defervescence AND ≥ 50 % CRP decrease at 72 h on carbapenem monotherapy.
Measured: three days
Carbapenem Plus Anti-Gram-Positive Agent Clinical Success Rate
Proportion achieving defervescence AND ≥ 50 % CRP decrease at 72 h after adding vancomycin or linezolid.
Measured: three days
Antifungal Therapy Biomarker Response Rate
Proportion with ≥ 50 % reduction in serum galactomannan (Platelia™ ELISA) or β-D-glucan (Fungitell™) at 72 h post-antifungal initiation.
Measured: three days
CRE/MDR-GNB Eradication Rate After CAZ-AVI Plus Aztreonam
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.
Measured: three days
Incidence of Adverse Events Assessed by CTCAE v5.0 (Entire Course)
Number and grade of drug-related cardiac, hepatic, renal, or allergic adverse events captured through CTCAE v5.0 forms.
Measured: From first antimicrobial dose to 30 days post-therapy
All-Cause Mortality Rate
Proportion of participants who die from any cause within 30 days after enrolment.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2025
- Study start22 Sep 2025 (estimated)
- Primary completion22 Sep 2027 (estimated)
- Study completion22 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Febrile NeutropeniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanxi Bethune Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07204522
- Sponsor's protocol ID
- ShanxiBethuneH3
- Status last verified
- Sep 2025
- First submitted
- 15 Sep 2025
- Last updated
- 2 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study on the Efficacy of Empirical Antimicrobial Therapy in Febrile Neutropenia.
- ClinicalTrials.gov ID
- NCT07204522
- Acronym / sponsor ID
- ShanxiBethuneH3
- Conditions
- Febrile Neutropenia
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Shanxi Bethune HospitalUniversity, hospital or other
- Study start
- 22 Sep 2025 (estimated)
- Primary completion
- 22 Sep 2027 (estimated)
- Study completion
- 22 Sep 2027 (estimated)
- First posted
- 2 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarbapenemsFirst-line empirical agent for febrile neutropenia complicating hematologic malignancies: carbapenem. | Drug | – |
| Anti-Gram-positive agentEscalation 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 agentIf 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 + AztreonamIf 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. | Drug | – |
Primary outcome
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.
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.
Procalcitonin Plasma Concentration Change (ng/mL)
Time frame: Two days
Absolute decrease from baseline in PCT measured by electrochemiluminescence immunoassay at 48 h.
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.
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.
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.
6 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Febrile Neutropenia, run by Shanxi Bethune Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Symptom Resolution Rate by Patient-Reported Temperature Diary (time frame: two days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2025.