NCT07051525

Early Versus Late Stopping of Antibiotics in Adults With High-risk Hematological Malignancies/Receiving Cellular Therapies and Fever

Early Versus Late Stopping of Antibiotics in Adults With High Risk Haematological Malignancies/Receiving Cellular Therapies and Fever (ELSA- Adult)

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 214 (estimated)
• Sponsor: Peter MacCallum Cancer Centre, Australia · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Pre-neutropenic fever (PNF) (fever following chemotherapy but before developing low white cells) and neutropenic fever (NF) (fever in the setting of low white cells) are very common after chemotherapy for acute leukemia, bone marrow transplantation or Chimeric Antigen Receptor T-cell (CAR T) therapy. Often, there is no bacterial cause for fever found, and in the setting of a well patient with resolved fever, some studies have shown it to be safe to cease antibiotic therapy which was commenced at the onset of fever. This reduces the overall exposure to antibiotics, which can be beneficial to the patient (reduced risk of resistant bugs emerging, reduced serious side effects). However, some subgroups of high-risk patients have been underrepresented in these studies (in particular, those who have received a bone marrow transplant from a donor, those with longer duration of low white cells) and none have been performed in Australia, hence applying this data to our setting and patient groups is indirect and further data are needed. This study plans to recruit participants who have received chemotherapy for acute leukemia or a stem cell transplant (either their own cells or a donor's cells) or CAR T-cell therapy and perform a trial to compare early stopping of antibiotics (STOP arm) to the standard of care, which traditionally involves continuing antibiotics until the white cell count reaches above a specific threshold. The primary study outcome is duration of days free of antibiotics within 28 days of study allocation. The investigators will also observe for important clinical outcomes including rates of fever recurrence, bloodstream and other infections, intensive care admission and mortality. Patients will stay in hospital during this period, even in the setting of stopping antibiotics, and these antibiotics can be recommenced urgently according to the sepsis protocol if there is concern for infection.

Detailed description

This study is designed to assess the safety, benefits and impacts of early cessation of empiric antibiotics in all fever (both pre-neutropenic (PNF) and neutropenic (NF)) that develops post conditioning or chemotherapy until count recovery in high-risk hematology patients who meet clear inclusion criteria. This is in recognition of the fact that both PNF and NF are often not infective in nature, and that cessation is likely an important and safe approach in both scenarios. Secondly, the patient's pre-neutropenic and neutropenic status is highly fluid and can rapidly change from one to the other (within a day), making strict definitions of neutropenia arbitrary and not particularly useful for implementation in the clinical setting. Furthermore, as a programmatic-type intervention that is embedded in clinical workflow, approaching high-risk patients with fever in a standardized way would enable consistency and inform clear and concise management protocols. Stratification will allow for assessment of each patient sub-group to provide more granular data. As an Australian first, this study will exploit the full potential of electronic medical record (EMR) systems, embedding all key aspects of the trial including screening, randomization and data collection into standard clinical and EMR workflows. This highly novel and innovative clinical trial methodology has the potential to improve trial efficiency, data quality and transferability between healthcare centers and will systematically evaluate the barriers and enablers of embedded trials (ELSA-EMR). The study hypothesizes that early cessation of antibiotics in adult patients with high risk fever is safe, acceptable, cost-effective and will minimize an unnecessarily prolonged health care intervention

Conditions

• Leukemia
• CART Therapy
• Transplantation, Stem Cell
• Infections, Bacterial

Interventions

Type	Name	Description
DRUG	Early antibiotic cessation alert	For all patients, antibiotics will be commenced at onset of fever. For those in the intervention arm an alert will fire in the electronic medical record once a patient is afebrile for 48-96 hours and clinically stable.

Timeline

• Start date: 2025-12-03
• Primary completion: 2027-12-05
• Completion: 2028-02-05
• First posted: 2025-07-04
• Last updated: 2025-12-15

Locations

2 sites across 1 country: Australia