Short Antibiotic Treatment in High Risk Febrile Neutropenia

NCT05786495 | Recruiting

• 1 other identifier: EASE ANTIBIOTICS pilot trial
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 4

Brief Summary

Infections are a common complication in patients with cancer. They are a significant cause of complications and death in this population. Patients with cancer and low neutrophil counts due to chemotherapy or disease often have a fever and receive antibiotic treatment. The optimal duration of this treatment is largely unknown. Late, there have been some data suggesting the safety of early discontinuation of antibiotics, though most centers still give more prolonged antibiotic therapies in this situation. The unnecessary prolonged antibiotic use may increase infections with multi-drug-resistant bacteria, which carry a high death rate. Also, an increase in infections caused by Clostridioides difficile and an increase in fungal infections can happen. However, some are concerned that stopping antibiotics while the neutrophil count is still low will result in life-threatening infections. Our study aims to test whether shorter antibiotic treatment in these situations is as safe as more prolonged treatment, resulting in better antibiotic prescription practices in this population.

Conditions

Febrile Neutropenia

Outcome Measures

Primary Outcomes (3)

• Recruitment

  number of patients enroled per site per month

  through study completion, approximately 2 years

• Adherence

  percentage of participants that adhered to the allocated intervention (meaning they stopped antibiotics within 2 days of the intervention they were randomized to)

  30 days from randomization

• Complete outcome data

  percentage of participants that were lost to follow up

  30 days from randomization

Secondary Outcomes (15)

• Rate of all-cause mortality

  30 days from randomization

• Rate of transfer to the ICU

  30 days from randomization

• Rate of any clinically or microbiologically documented infection

  30 days from randomization

• Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR) analysis

  30 days from randomization

• total febrile days

  30 days from randomization

Study Arms (2)

Short treatment

EXPERIMENTAL

Antibiotic treatment will be stopped at the time of allocation to the intervention group

Other: Early Discontinuation of Antibiotics

Prolonged treatment

ACTIVE COMPARATOR

Antibiotic treatment will be continued until the resolution of neutropenia (ANC \> 0.5x109/L)

Other: Standard of Care

Interventions

Early Discontinuation of Antibiotics OTHER

Antibacterial treatment (i.e piperacillin/tazobactam, ceftazidime, cefepime, meropenem, vancomycin, amikacin, tobramycin, ciprofloxacin) will be stopped after 72 hours of treatment and defervescence for 24 hours, irrespective of neutrophil count

Short treatment

Standard of Care OTHER

Antibacterial treatment (i.e piperacillin/tazobactam, ceftazidime, cefepime, meropenem, vancomycin, amikacin, tobramycin, ciprofloxacin) will be continued until resolution of neutropenia

Prolonged treatment

Eligibility Criteria

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

You may qualify if:

• Age 18 years and older.
• The patient either has acute leukemia (AML, ALL or mixed-phenotypic acute leukemia) and is undergoing induction, re-induction or salvage chemotherapy or undergoing allogeneic HSCT and receiving conditioning chemotherapy and/or radiation.
• Documented febrile neutropenia as defined by the IDSA guidelines \[1\]:
• Single oral temperature of ≥38.3°C or at least two measurements of ≥38.0°C in an interval of ≥1 hour.
• ANC ≤ 0.5x109/L.
• Patient without a clinically or microbiologically documented infection (CDI/MDI).
• We will require the following criteria to rule out infection:
• No focus of infection on a thorough history and physical examination at baseline and daily.
• Negative blood cultures after at least two sets of blood cultures have been taken. For example, the growth of coagulase-negative staphylococci, diphtheroids or Bacillus spp. from a single set will be considered contamination if another set of blood cultures is negative. Therefore, additional blood cultures will be taken in this case.
• Other cultures will be taken as indicated.
• A negative chest XR or CT scan (which will be performed according to the physician's discretion) for patients with symptoms of cough or chest pain.
• The subject will comply with the following criteria:
• Received empirical antibiotics for at least 72 hours AND
• Is afebrile for at least 24 hours AND
• Is still neutropenic (ANC ≤0.5x109/L).

You may not qualify if:

• Concurrent participation in another interventional trial.
• The patient has received empirical antibiotics for more than seven days from the onset of the febrile neutropenic episode.
• Septic shock at the onset of the episode or 72 hours (defined as persisting hypotension requiring vasopressors to maintain a MAP ≥ 65 mmHg and having a serum lactate level \> 2 mmol/L despite adequate volume resuscitation).
• Patients with febrile neutropenia secondary to the treatment for solid malignancies, autologous HSCT, CAR-T cell therapy, hematologic malignancies besides acute leukemia when not in the context of allogeneic HSCT, AML treated with consolidation chemotherapy, or ALL treated with intensification and maintenance phase of chemotherapy.
• Clinically or microbiologically documented infections except for probable or proven invasive fungal disease diagnosed a-priori and treated.
• Patients receiving their induction chemotherapy or allogeneic HSCT as outpatients.
• We will not allow the enrollment of patients who have been previously enrolled in this study.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (4)

Alberta Health Services

Edmonton, Canada

RECRUITING

London Health Sciences Centre

London, Canada

RECRUITING

University Health Network

Toronto, Canada

RECRUITING

Vancouver General Hospital

Vancouver, Canada

RECRUITING

MeSH Terms

Conditions

Febrile Neutropenia

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Shahid Husain, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shahid Husain, MD

CONTACT

4163404800; shahid.husain@uhn.ca

Roni Bitterman, MD

CONTACT

4163404800; roni.bitterman@uhn.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2023
• First Posted: March 27, 2023
• Study Start: October 1, 2023
• Primary Completion: December 31, 2025
• Study Completion: February 28, 2026
• Last Updated: July 17, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: from 6 months until 24 months after article publication
• Access Criteria: scientific research approved by an ethical board. Data requestors need to sign a data access agreement to gain access.

Locations

CA (4)