Antibiotic Duration and Outcomes in High-Risk Febrile Neutropenia Patients

NCT07372131 | Recruiting DMC

• 1 other identifier: PERaSTrA
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if a personalized duration of antibiotic therapy, based on clinical stability, is as effective as a standard duration of at least 10 days in hospitalized patients with hematologic malignancies (such as leukemia or lymphoma) who develop febrile neutropenia and Gram-negative bacteraemia. The main questions it aims to answer are:

• Can a personalized antibiotic duration increase the number of days free from anti-Gram-negative therapy within 28 days without compromising patient safety?
• How does the duration of antibiotic therapy (short vs. prolonged) affect the rate and modality of gut microbiota reconstitution? Researchers will compare:
• Group A (Personalized Duration): Antibiotics are stopped after the patient maintains clinical stability (no fever and stable vital signs) for 72 consecutive hours.
• Group B (Standard of Care): Antibiotics are continued for a standard duration, typically at least 10 days, based on current clinical surveys and physician decision. Participants will:
• Be randomized to receive either the personalized or the standard duration of antibiotic therapy once a Gram-negative infection is confirmed in the blood.
• Be monitored for 28 days to assess for new fever episodes, recurrence of infection, and overall survival.
• If participating in the microbiological sub-study, provide biological samples (blood, feces, and rectal swabs) at specific time points (at the onset of fever, at the end of treatment, and at day 28).
• Undergo specialized laboratory testing (Whole Metagenomic Sequencing) on the collected samples to evaluate the evolution of their intestinal and blood microbiota and the presence of antibiotic-resistant genes.

Conditions

Bloodstream Infection; Gram Negative Infections; Bacteraemia Caused by Gram-Negative Bacteria; Febrile Neutropenia (FN)

Keywords

Antibiotics; Bloodstream Infection; Hematological patients with febrile neutropenia; Gram-negative

Outcome Measures

Primary Outcomes (1)

• Days Free from Anti-Gram-Negative Antibiotic Therapy within 28 days

  Number of days that the participant is alive and free from any anti-Gram-negative antibiotic therapy, calculated from the date of the index blood culture collection (onset of infection) up to Day 28. Antibiotics active exclusively on Gram-positive bacteria (e.g., glycopeptides, daptomycin) and fluoroquinolone prophylaxis are excluded from this calculation.

  From the date of index blood culture collection (Day 0) up to Day 28

Secondary Outcomes (7)

• Incidence of New Fever Episodes

  From the end of antibiotic therapy up to Day 28

• 28-day All-cause Mortality

  Up to Day 28

• Relapse of Bloodstream Infection (BSI) by the Same Pathogen

  From the end of antibiotic therapy up to Day 28

• Recurrent BSI by Gram-negative Bacteria

  From the end of antibiotic therapy up to Day 28

• Emergence of Multi-Drug Resistant Organisms (MDRO)

  Within 90 days from the index blood culture collection

Study Arms (2)

Standard of Care

ACTIVE COMPARATOR

Standard of care antibiotic therapy with a suggested minimum duration of 10 days.

Other: Standard of Care Antibiotic Duration

Personalized Duration

EXPERIMENTAL

Patients in this arm will receive antibiotic therapy for a duration guided by clinical stability. Antibiotics will be discontinued after 72 consecutive hours of clinical stability, defined as apyrexia (Tc \< 38°C) for at least 48 hours and stable or improved qSOFA score.

Other: Clinical Stability-Driven Antibiotic Discontinuation Strategy

Interventions

Standard of Care Antibiotic Duration OTHER

This intervention follows the standard clinical practice for treating Gram-negative bacteraemia in hematological patients. The duration of therapy is not fixed by a stability-driven rule but is based on the treating physician's decision, with a suggested minimum of 10 days.

Also known as: B

Standard of Care

Clinical Stability-Driven Antibiotic Discontinuation Strategy OTHER

A therapeutic strategy where the duration of antibiotic treatment for Gram-negative bacteraemia is determined by the achievement of clinical stability (defined as apyrexia for 48h and stable/improved qSOFA score) maintained for 72 consecutive hours

Also known as: A

Personalized Duration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Humanitas University: lead
• Ministry of education, university and research, Italy: collaborator

Study Sites (1)

Microbiology and Virology - IRCCS Humanitas Research Hospital

Rozzano, Milan, 20089, Italy

RECRUITING

Related Publications (19)

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MeSH Terms

Conditions

Sepsis; Febrile Neutropenia

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neutropenia; Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Study Officials

• Valeria Cento, MD, PhD

  Humanitas University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valeria Cento, MD, PhD

CONTACT

0282243166; valeria.cento@hunimed.eu

Michele Bartoletti, MD, PhD

CONTACT

0282243568; michele.bartoletti@hunimed.eu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Operative Unit of Microbiology and Virology

Study Record Dates

• First Submitted: January 20, 2026
• First Posted: January 28, 2026
• Study Start: May 10, 2025
• Primary Completion: February 28, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: January 28, 2026

Record last verified: 2026-01

Locations

IT (1)