Shortening antibiotic treatment for patients with febrile neutropenia

Early Discontinuation of Antibiotics for Unexplained Febrile Neutropenia: a Pilot Randomized Controlled Trial- EASE ANTIBIOTICS Pilot Trial

This study is testing if stopping antibiotics earlier is safe and effective for cancer patients with febrile neutropenia, compared to the usual longer treatment, to see if it can lower the risk of complications and infections.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, radiation
• Locations: 4 sites (Edmonton and 3 other locations)
• Trial ID: NCT05786495 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and efficacy of early discontinuation of antibiotic treatment in patients with febrile neutropenia, a common complication in cancer patients undergoing chemotherapy. It aims to determine whether shorter antibiotic courses can reduce the risk of antibiotic resistance and other complications without increasing the risk of life-threatening infections. Participants will be randomized to receive either early discontinuation of antibiotics or standard prolonged treatment. The study will include patients with acute leukemia undergoing chemotherapy and will assess outcomes related to infection rates and safety.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with acute leukemia undergoing chemotherapy who have documented febrile neutropenia without a confirmed infection.

Not a fit: Patients with clinically or microbiologically documented infections or those with other underlying conditions that complicate febrile neutropenia may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to safer antibiotic use and reduced complications for patients with febrile neutropenia.

How similar studies have performed: Recent studies have suggested that early discontinuation of antibiotics in similar populations may be safe, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age 18 years and older.
2. 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.
3. Documented febrile neutropenia as defined by the IDSA guidelines \[1\]:

   1. Single oral temperature of ≥38.3°C or at least two measurements of ≥38.0°C in an interval of ≥1 hour.
   2. ANC ≤ 0.5x109/L.
4. Patient without a clinically or microbiologically documented infection (CDI/MDI).

   We will require the following criteria to rule out infection:
   1. No focus of infection on a thorough history and physical examination at baseline and daily.
   2. 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.
   3. Other cultures will be taken as indicated.
   4. 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.
5. The subject will comply with the following criteria:

   1. Received empirical antibiotics for at least 72 hours AND
   2. Is afebrile for at least 24 hours AND
   3. Is still neutropenic (ANC ≤0.5x109/L).

Exclusion Criteria:

1. Concurrent participation in another interventional trial.
2. The patient has received empirical antibiotics for more than seven days from the onset of the febrile neutropenic episode.
3. 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).
4. 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.
5. Clinically or microbiologically documented infections except for probable or proven invasive fungal disease diagnosed a-priori and treated.
6. Patients receiving their induction chemotherapy or allogeneic HSCT as outpatients.
7. We will not allow the enrollment of patients who have been previously enrolled in this study.

Where this trial is running

Edmonton and 3 other locations

• 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)

Study contacts

• Principal investigator: Shahid Husain, MD — University Health Network, Toronto
• Study coordinator: Shahid Husain, MD

Conditions Febrile Neutropenia