Personalized antibiotic duration for high-risk febrile neutropenia with Gram-negative bloodstream infection
Appropriate Management of Bacteriemic Febrile Neutropenia in High-Risk Hematological Patients. Relationship Between Duration of Antibiotic Administration, Outcome and Resistance Profile
This trial tests whether stopping antibiotics after a patient with a blood cancer and febrile neutropenia has been clinically stable for 72 hours is as safe and lets them spend more days off anti–Gram-negative antibiotics than the usual at least 10-day approach.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 172 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Humanitas University Academic / other |
| Drugs / interventions | CAR-T, chimeric antigen receptor, chemotherapy |
| Locations | 1 site (Rozzano, Milan) |
| Trial ID | NCT07372131 on ClinicalTrials.gov |
What this trial studies
This is a randomized, open-label trial that assigns hospitalized patients with hematologic malignancies and Gram-negative bacteraemia 1:1 to either stop antibiotics once they maintain clinical stability for 72 consecutive hours or to continue standard care with a suggested minimum of 10 days of therapy. Clinical stability is defined by sustained resolution of fever and stable or improving qSOFA score. A parallel microbiological sub-study uses shotgun metagenomic sequencing of stool, rectal swabs, and blood at baseline, end of treatment, and day 28 to compare microbiome recovery and acquisition of antimicrobial-resistance genes. All participants are followed clinically through day 28 to capture safety and antibiotic-free days outcomes.
Who should consider this trial
Good fit: Hospitalized adults with a hematologic malignancy receiving or planned for chemotherapy/BMT/CAR‑T who develop febrile neutropenia with documented Gram-negative bacteraemia and expected neutropenia ≥7 days are the intended candidates.
Not a fit: Patients with contextual pneumonia, other uncontrolled or complicated infections, non–Gram-negative bloodstream infections, or those who remain clinically unstable are unlikely to benefit from the personalized early-stop approach.
Why it matters
Potential benefit: If successful, this approach could reduce unnecessary antibiotic exposure, lower risk of resistant organisms, and speed recovery of the healthy gut microbiome for patients with febrile neutropenia and Gram-negative bloodstream infection.
How similar studies have performed: Shorter or stability-guided antibiotic courses have shown promise in some non-neutropenic infections, but randomized data specifically for high-risk febrile neutropenia with Gram-negative bacteraemia are limited, so this approach is relatively novel in this population.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Diagnosed with a hematologic malignancy that is candidate for treatment with chemotherapy or bone marrow transplantation or chimeric antigen receptor T cell therapy (CAR-T) * Diagnosis of febrile neutropenia defined according to the guidelines of the Infectious Disease Society of America, IDSA; ref: Freifeld, A.G., et al., Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis, 2011. 52(4): p. e56-93.) as: Fever: single record of oral temperature \>=38.3°C or a temperature \>=38.0°C sustained over a period of one hour; Neutropenia: absolute neutrophil count \< 1000 cells/microL; Expected duration of neutropenia \>= 7 days * Diagnosis of bacteraemia defined by positive blood cultures (at least 1 vial positive for a non-contaminating microorganism) * Isolation of Gram-Negative species Exclusion Criteria: * Contextual diagnosis of pneumonia * Contextual diagnosis of intra-abdominal infection, in particular: neutropenic enterocolitis/typhlitis or biliary tract infection * Persistently positive blood cultures at randomization * Any condition that endangers the safety of the patient based on the judgment of the treating physician
Where this trial is running
Rozzano, Milan
- Microbiology and Virology - IRCCS Humanitas Research Hospital — Rozzano, Milan, Italy (Recruiting)
Study contacts
- Principal investigator: Valeria Cento, MD, PhD — Humanitas University
- Study coordinator: Valeria Cento, MD, PhD
- Email: valeria.cento@hunimed.eu
- Phone: 0282243166
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.