Clinical trial NCT05174546: New Diagnostics in Neutropenia
Official title: Performance of Emerging Microbiological Techniques for the Diagnosis of Severe Infections in Neutropenic Patients With Haematological Malignancies
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Febrile Neutropenia
Lead sponsor: The University of Queensland
Sponsor class: OTHER
First posted: 2021-12-30
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients affected by acute leukemia and bone marrow transplant recipients who are admitted to the Haematology Unit and are expected to encounter chemotherapy-induced or pre/post-transplant neutropenia during the course of hospital admission, will be approached by research staff to discuss participation. Study aims and design will be discussed and the opportunity to read the Patient Information and Consent Form and ask questions will be provided. Patients or their representative will be provided an informed consent form to confirm participation, and consent will be obtained prior to episodes of febrile neutropenia.

In consenting patients, in the subsequent case of febrile episodes during neutropenia, the collection of blood samples for T2MR assessment will be performed in addition to blood cultures ordered as per standard of care.

Brief summary: Mortality due to bloodstream infections in patients with neutropenia and haematological malignancies is high and optimal management is hampered by long turnaround times of conventional blood cultures.

This is an observational study to assess the performance of T2 magnetic resonance, in diagnosing proven, probable and possible bloodstream infections as well as its theoretical impact on antimicrobial prescriptions in neutropenic patients with acute leukemia and bone marrow recipients.

Detailed description: Study Background

In patients with haematological malignancies, neutropenia often leads to the development of severe infections, including bloodstream, which are characterized by high mortality. Patients' management can be challenging as conventional diagnostic methods for the diagnosis of such infections are affected by several limitations, including limited sensitivity and long turnaround time.

T2 Magnetic Resonance (T2MR) is a new technology able to identify pathogens directly from whole blood in few hours, and preliminary data showed how it might have higher sensitivity compared to blood cultures.

Study Aims

* To assess the performance of the T2MR (including the T2Candida, T2Bacteria and T2Resistance) in diagnosing proven, probable, and possible bloodstream infection (BSI) due to T2 on-panel pathogens, in patients affected by haematological malignancies with febrile neutropenia, including patients with acute leukaemia and bone marrow transplant recipients.
* To assess the mean time to results of the T2MR 3 panels as compared to blood cultures. These will be considered as an estimate of time to optimal treatment in proven, probable, and possible BSI.
* To estimate the potential impact of T2MR results on antimicrobial modifications in neutropenic patients with proven/probable and possible BSI.

Methods

Prospective observational study. Patients with acute leukemia or bone marrow transplant recipients and febrile neutropenia, admitted to the Haematology ward, will be consecutively enrolled in the study. 100 consecutive febrile episodes will be included in the study.

At the time of blood culture collection (ordered as per standard of care), blood samples for T2MR (including T2Bacteria, T2Candida and T2Resistance) will be also collected.

The performance of the T2 assays will be compared to that of proven, probable, and possible BSI defined by standard of care laboratory practices due to T2 on-panel pathogens, and time to results will be assessed as an estimate of time to optimal treatment.

Moreover the potential impact of T2 positive results on antimicrobial modifications will be estimated including escalation, de-escalation and antimicrobial change.

Proven BSI is defined by a positive blood culture; probable BSI is defined by a negative blood culture but a positive T2 result if the T2-detected organism is isolated within 21 days from another clinical specimen; possible BSI is defined as a negative blood culture but a positive T2 result in the absence of supporting culture data if the T2-detected organism or resistance gene was a plausible cause of infection.

Data analysis

Sensitivity, specificity, and predictive values will be calculated using proven, probable, and possible BSI as a reference, with 95% confidence intervals.

Mean time to T2 results will be compared to mean time to blood cultures results.

Eligibility criteria: Inclusion Criteria:

Adult patients (\> 18 years old) affected by acute leukaemia and/or recipients of bone marrow transplantation for any disease indication (during the pre and post-transplant phase) who develop febrile neutropenia, where blood cultures (and possibly bronchoscopy) are ordered as per standard of care.

Febrile neutropenia is defined as:

* an ANC of \<500 cells/mm3
* a single temperature measurement of ≥38.0°C

Exclusion Criteria:

* Patients not able to provide informed consent
* Death is deemed imminent

Primary outcomes:
measure: Sensitivity and specificity of T2MR as compared to Blood Cultures for the diagnosis of proven, probable, and possible BSI as previously defined
timeFrame: 01/04/2022 - 31/03/2023
Secondary outcomes:
measure: In patients with positive T2 results: Mean time to result of T2MR
timeFrame: 01/04/2022 - 31/03/2023
measure: In patients with positive T2 results: percentage of potential antimicrobial modifications according to T2 results
timeFrame: 01/04/2022 - 31/03/2023
Other outcomes:
Locations:
city: Brisbane
country: Australia
facility: Royal Brisbane Hospital
state: Queensland
Study officials:
References: