Short Antibiotic Treatment for Febrile Neutropenia

Recruiting at 3 trial locations

Overseen By Roni Bitterman, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must be taking: Antibiotics

Disqualifiers: Septic shock, Solid malignancies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 30 days

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a shorter course of antibiotics is as safe and effective as a longer one for cancer patients with low white blood cell counts and a fever. The focus is on reducing unnecessary antibiotic use, which can lead to drug-resistant infections and other complications. Participants will be divided into two groups: one will stop antibiotics early (Early Discontinuation of Antibiotics), and the other will continue with the Standard of Care until their white blood cell count improves. Those with acute leukemia and recent fever but no clear infection, who have been on antibiotics for at least three days without a fever for a day, might be suitable candidates.

As an unphased trial, this study offers a unique opportunity to contribute to important research that could improve treatment protocols for future patients.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that stopping antibiotics early for patients with febrile neutropenia (a condition with fever and low white blood cell count) can be safe in some cases. One study found that patients with a low-risk episode of febrile neutropenia did well even when antibiotics were stopped early. Another study showed that shorter antibiotic treatments led to fewer days with fever compared to longer treatments.

However, some sources have not strongly confirmed the safety of stopping antibiotics before the low white blood cell count improves. This uncertainty means it's not clear if it's always safe to stop early for everyone. Risks include the chance of a serious infection if treatment stops too soon.

In summary, while stopping antibiotics early has shown promise in some studies, it may not be safe for all patients. The evidence suggests it can be safe for those considered low-risk, but more research is needed to confirm this for everyone. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the trial exploring short antibiotic treatment for febrile neutropenia because it challenges the standard practice of prolonged antibiotic courses. Unlike the traditional approach, which continues antibiotics until neutropenia resolves, the short treatment option stops antibiotics when patients are assigned to the intervention group. This could reduce unnecessary antibiotic exposure, minimize side effects, and lower the risk of antibiotic resistance, all while maintaining patient safety. If successful, this approach could revolutionize how febrile neutropenia is managed, making treatments more efficient and patient-friendly.

What evidence suggests that this trial's treatments could be effective for febrile neutropenia?

This trial will compare short antibiotic treatment with prolonged treatment for febrile neutropenia. Research has shown that stopping antibiotics early in patients with febrile neutropenia (a fever and low white blood cell count) can be as safe as longer courses. Studies have found that people on shorter antibiotic courses experience fewer days with fever compared to those on longer courses. Specifically, one study found that reducing or stopping treatment early doesn't increase the risk of death and may even lower it. Evidence suggests that shorter antibiotic treatments are safe for patients with a low-risk episode of febrile neutropenia, regardless of their white blood cell count. This approach can help prevent infections from drug-resistant bacteria and other complications. ^{2 3 4 5 6}

Who Is on the Research Team?

Shahid Husain, MD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for adults over 18 with acute leukemia or undergoing stem cell transplant, who have low neutrophil counts due to treatment and develop a fever without any documented infection. They must have had negative blood cultures after antibiotics for at least 72 hours.

Inclusion Criteria

I am receiving treatment for acute leukemia, including chemotherapy or a stem cell transplant.

I have had a fever with very low white blood cells as per IDSA guidelines.

I do not have any infections confirmed by clinical or lab tests.

Exclusion Criteria

Concurrent participation in another interventional trial

I've been on antibiotics for over a week for a fever due to low white blood cells.

Patients who have been previously enrolled in this study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either early discontinuation or prolonged antibiotic treatment based on randomization

30 days

Regular monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of antibiotic resistance and adverse events

30 days

Extension

Long-term monitoring for recruitment rate and adherence to intervention

Approximately 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Early Discontinuation of Antibiotics
• Standard of Care

Trial Overview The study compares the safety of stopping antibiotics early versus the standard longer treatment in cancer patients with febrile neutropenia. It aims to determine if shorter treatments can prevent complications from drug-resistant bacteria and other infections.

How Is the Trial Designed?

Group I: Short treatment Experimental Treatment 1 Intervention

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

Group II: Prolonged treatment Active Control 1 Intervention

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

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a study of 129 pediatric cancer patients with febrile neutropenia, a once-daily antibiotic regimen of ceftriaxone plus amikacin allowed for a significantly shorter hospital stay (median 5 days) compared to imipenem monotherapy (median 9 days), indicating improved hospital utilization.

The once-daily regimen was safe, with no adverse events reported in 84% of patients treated as outpatients, and it also resulted in lower treatment costs, making it a beneficial alternative for managing febrile neutropenia in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early hospital discharge versus continued hospitalization in febrile pediatric cancer patients with prolonged neutropenia: A randomized, prospective study. Ahmed, N., El-Mahallawy, HA., Ahmed, IA., et al.[2013]

The implementation of the ECIL-4 antibiotic de-escalation protocol in 446 high-risk hematological patients led to a significant reduction in overall mortality (0.7% vs 2.7% in the historic cohort), indicating its effectiveness in improving patient outcomes.

Despite a higher incidence of bacteremia in the ECIL-4 group (46.9% vs 30.5%), there was no increase in severe complications like septic shock or ICU admissions, suggesting that the protocol is safe and does not compromise patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Antibiotic De-escalation and Discontinuation in High-Risk Hematological Patients With Febrile Neutropenia: A Single-Center Experience. Verlinden, A., Jansens, H., Goossens, H., et al.[2022]

The management of febrile neutropenia has evolved significantly over the past 20 years, focusing on adapting treatment strategies to combat antibiotic-resistant strains and improving patient outcomes through better prognostic factors.

New approaches include the use of home therapy for select patients, the application of cytokines to enhance bone marrow recovery, and improved strategies for diagnosing and treating fungal infections associated with neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of neutropenic infection: trends towards monotherapy? Klastersky, J.[2019]

In a study of 124 adult cancer patients with febrile neutropenia in Lebanon, 86.23% received appropriate antibiotic therapy according to IDSA guidelines, indicating a generally good adherence to recommended practices for antibiotic use.

However, there was significant inconsistency in antifungal and antiviral treatments, with many patients receiving inappropriate drug choices, doses, and durations, highlighting a need for improved adherence to guidelines in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Antimicrobial Utilization among Cancer Patients with Febrile Neutropenia at the Lebanese Hospitals. Cherri, S., Malaeb, D., Shouman, L., et al.[2023]

In a study of 536 episodes of febrile neutropenia across four Brazilian medical centers, vancomycin was underutilized, being administered in only 5% of cases despite guidelines recommending its use in 27% of instances.

The study highlights the need for better adherence to treatment guidelines for febrile neutropenia, as the low use of vancomycin could impact patient outcomes, especially given the presence of resistant infections like methicillin-resistant Staphylococcus aureus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low utilization of vancomycin in febrile neutropenia: real-world evidence from 4 Brazilian centers. Ramos, JF., Pereira, AD., Seiwald, MCN., et al.[2023]

In a study of 828 patients with febrile neutropenia, treatment with ceftriaxone alone resulted in a 70.8% response rate, significantly higher than the 56.9% response rate seen with combination therapy, indicating its efficacy as a single-agent treatment.

Ceftriaxone was found to be safe and effective, particularly in low-risk patients, suggesting that single-agent regimens could be a viable treatment option for managing febrile neutropenia in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftriaxone monotherapy in the treatment of low-risk febrile neutropenia. Karthaus, M., Wolf, HH., Kämpfe, D., et al.[2018]

In a study of 40 patients with febrile neutropenia after chemotherapy for haematologic malignancies, adherence to established antibiotic guidelines was reasonable, with valid clinical reasons for non-compliance in all cases.

Only 31% of episodes started with the recommended first-line antibiotic (cefepime), and while there were 3 deaths, none were linked to adherence issues, suggesting that the guidelines may need simplification to improve compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of antibiotics in a haematology ward--an audit. Wong, GC., Tan, BH.[2020]

In a study of 180 neutropenic patients with positive blood cultures, the traditional antibiotic protocol (piperacillin, gentamicin, and cefazolin) was appropriate for 85% of bacteremia episodes, showing its continued relevance in treating febrile neutropenia.

The presence of antibiotic-resistant bacteria in patients was linked to higher mortality rates, highlighting the importance of using broad-spectrum antibiotic combinations to maximize treatment effectiveness in neutropenic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empiric antibiotic protocols for cancer patients with neutropenia: a single-center study of treatment efficacy and mortality in patients with bacteremia. Kleinhendler, E., Cohen, MJ., Moses, AE., et al.[2023]

Ambulatory management of febrile neutropenia is safe and shows improved quality of life for patients, making it a viable alternative to hospitalization.

This approach is also more cost-effective than traditional inpatient care, suggesting it could be a beneficial strategy for managing low-risk patients with febrile neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ambulatory management of low-risk febrile neutropenia in adult oncological patients. Systematic review. Forcano-Queralt, E., Lemes-Quintana, C., Orozco-Beltrán, D.[2023]

Among 2131 adult patients receiving myelosuppressive chemotherapy, 16.8% experienced febrile neutropenia, with the highest risk occurring during the first cycle of treatment (8.1%).

Most cases (83.2%) required inpatient treatment, leading to an average hospital stay of 8.4 days and a mortality rate of 8.1%, highlighting the serious consequences of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence, treatment, and consequences of chemotherapy-induced febrile neutropenia in the inpatient and outpatient settings. Weycker, D., Barron, R., Kartashov, A., et al.[2022]

In a study of 71 acute myeloid leukemia patients with febrile neutropenia, a short course of antibiotics (≤7 days) was found to be as effective as longer treatments for bloodstream infections, with only 7.6% of episodes relapsing within 30 days after stopping antibiotics.

The only significant risk factor for relapse was the duration of neutropenia, suggesting that managing neutropenia may be crucial in preventing infections, and these promising results warrant further investigation in prospective studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of antibiotic short course for bloodstream infections in acute myeloid leukemia patients with febrile neutropenia: A retrospective comparative study. Metais, A., Torregrosa Diaz, JM., Gallego Hernanz, MP., et al.[2023]

Prompt initiation of broad-spectrum antibiotic therapy for cancer patients experiencing febrile neutropenia significantly reduces early death and morbidity rates, highlighting the importance of timely treatment.

The study discusses three initial empiric therapy regimens and suggests that identifying low-risk patients could allow for effective outpatient treatment, potentially lowering economic and psychological burdens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibiotic Selection in the Treatment of Febrile Neutropenia: Current Approach and New Directions. Stefani, SD., Cadore, LP., Villaroel, RU., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6353178/

Early discontinuation of antibiotics for febrile neutropenia ... The number of days with fever was lower for people treated with short antibiotic courses compared to those treated with long antibiotic courses. In all trials ...

2. cochranelibrary.com cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012184.pub2/full

Early discontinuation of antibiotics for febrile neutropenia ... The number of days with fever was lower for people treated with short antibiotic courses compared to those treated with long antibiotic courses.

3. journals.asm.org journals.asm.org/doi/10.1128/aac.01597-24

Efficacy and safety of early antibiotic de-escalation in febrile ... Early de-escalation of BSA in patients with hematologic malignancies and developing FN after treatment significantly reduces mortality risk without increasing ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772610X25001102

Early discontinuation of empiric antibiotic therapy in ... This study provides evidence that early discontinuation of antibiotics in oncology patients with a low-risk episode of FN is safe, regardless of neutrophil ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06278896

Early Neutropenic Fever De-escalation of Antibiotics Study The trial aims to evaluate the safety and clinical outcomes of de-escalating antibiotic therapy among stable individuals diagnosed with neutropenic fever, in ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30605229/

Early discontinuation of antibiotics for febrile neutropenia ... We could make no strong conclusions on the safety of antibiotic discontinuation before neutropenia resolution among people with cancer with febrile neutropenia.