Antibiotic Duration and Outcomes in High-Risk Febrile Neutropenia Patients (PERaSTrA)

January 20, 2026 updated by: Valeria Cento, Humanitas University

Appropriate Management of Bacteriemic Febrile Neutropenia in High-Risk Hematological Patients. Relationship Between Duration of Antibiotic Administration, Outcome and Resistance Profile

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, open-label, randomized controlled trial. Upon confirmation of Gram-negative bacteraemia, eligible patients are randomized 1:1 to one of two treatment strategies:

  • Experimental Arm (Personalized Duration): Antibiotic therapy is discontinued once the patient achieves and maintains clinical stability for 72 consecutive hours. Clinical stability is defined as apyrexia (Tc < 38°C) for at least 48 hours and a stable or improving qSOFA score.
  • Control Arm (Standard of Care): Antibiotic therapy duration follows local clinical practice, with a suggested minimum duration of 10 days, consistent with current European and Asian hematological guidelines.

In parallel, a prospective observational microbiological sub-study will utilize Shotgun Metagenomic Next-Generation Sequencing (mNGS) to analyze the evolution of the intestinal and blood microbiota. The goal is to compare the rate of MDR organism colonization and the reconstitution of the healthy microbiome between the two antibiotic duration strategies.

All participants will undergo clinical monitoring until day 28. For those enrolled in the sub-study, biological samples (stool, rectal swabs, and blood) will be collected at baseline (V1), at the end of treatment (V4), and at the end of the study (V5). These samples will be analyzed to identify clinically significant bacteria and antibiotic-resistance genes.

Study Type

Interventional

Enrollment (Estimated)

172

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
    • Milan
      • Rozzano, Milan, Italy, 20089
        • Recruiting
        • Microbiology and Virology - IRCCS Humanitas Research Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard of Care
Standard of care antibiotic therapy with a suggested minimum duration of 10 days.
Other: Standard of Care Antibiotic Duration
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.
Other Names:
  • B
Experimental: Personalized Duration
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
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
Other Names:
  • A

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Days Free from Anti-Gram-Negative Antibiotic Therapy within 28 days
Time Frame: From the date of index blood culture collection (Day 0) up to Day 28
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of New Fever Episodes
Time Frame: From the end of antibiotic therapy up to Day 28
Number of participants experiencing a new episode of fever (Tc ≥ 38.3°C) occurring after a period of apyrexia of at least 72 hours
From the end of antibiotic therapy up to Day 28
28-day All-cause Mortality
Time Frame: Up to Day 28
Number of participants who died from any cause within 28 days from the onset of the index infection (date of first positive blood culture)
Up to Day 28
Relapse of Bloodstream Infection (BSI) by the Same Pathogen
Time Frame: From the end of antibiotic therapy up to Day 28
Number of participants with a new positive blood culture for the same Gram-negative pathogen identified in the index episode
From the end of antibiotic therapy up to Day 28
Recurrent BSI by Gram-negative Bacteria
Time Frame: From the end of antibiotic therapy up to Day 28
Number of participants experiencing a new episode of bloodstream infection caused by any Gram-negative bacteria different from the index pathogen
From the end of antibiotic therapy up to Day 28
Emergence of Multi-Drug Resistant Organisms (MDRO)
Time Frame: Within 90 days from the index blood culture collection
Number of participants with isolation of a new MDRO from recurrent positive blood cultures, or evidence of a worsened resistance profile compared to the index isolate
Within 90 days from the index blood culture collection
Incidence of Clostridioides difficile Infection (CDI)
Time Frame: Up to Day 28
Number of participants with a laboratory-confirmed diagnosis of Clostridioides difficile infection
Up to Day 28
Incidence of Antibiotic-Related Adverse Events
Time Frame: Up to Day 28
Number of participants experiencing adverse events (AE) judged by the investigator to be related to the antibiotic therapy (e.g., allergic reactions, renal toxicity)
Up to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Humanitas University

Collaborators

Ministry of education, university and research, Italy

Investigators

  • Principal Investigator: Valeria Cento, MD, PhD, Humanitas University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 10, 2025

Primary Completion (Estimated)

February 28, 2026

Study Completion (Estimated)

November 30, 2026

Study Registration Dates

First Submitted

January 20, 2026

First Submitted That Met QC Criteria

January 20, 2026

First Posted (Actual)

January 28, 2026

Study Record Updates

Last Update Posted (Actual)

January 28, 2026

Last Update Submitted That Met QC Criteria

January 20, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PERaSTrA

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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