PET/CT and Bacterial/Fungal PCR in High Risk Febrile Neutropenia

Study Overview
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Brief Summary
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Patients with acute leukaemia requiring induction or consolidation chemotherapy and those requiring a haematopoietic stem cell transplant are at high risk of fever and infection when they have low white cell counts (neutropenic fever). The causes of neutropenic fever are frequently unknown and patients are treated with broad antibiotics, without a clear target to what is being treated. This study will prospectively enroll patients who are receiving chemotherapy for acute leukaemia or for a stem cell transplant and compare the diagnostic utility of bacterial and fungal PCR performed directly off blood drawn, to the standard blood culture. Patients who have persistent fever after 72 hours of antibiotics will then be randomized to have either the interventional scan (PET/CT) or the conventional scan (standard CT) to look for a source of infection. Diagnostic yield, change in management and outcomes will be compared between arms.

Official Title
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Early Diagnosis and Treatment of Infections in Patients With Haematologic Malignancies: Examining Novel Diagnostics Including Bacterial and Fungal Multiplex PCR and FDG-PET Imaging

Conditions
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Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Haematopoietic Stem Cell Transplant, Autologous, Haematopoietic Stem Cell Transplant, Allogeneic, Febrile Neutropenia

Intervention / Treatment
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* Diagnostic Test: FDG-PET/CT
* Diagnostic Test: Conventional CT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: About to have an allogeneic haematopoietic stem cell transplant, OR About to have an autologous haematopoietic stem cell transplant, OR Commencing induction or consolidation chemotherapy with curative intent for acute myeloid or acute lymphoid leukaemia Exclusion Criteria: Current actively diagnosed infection prior to transplant or chemotherapy Allergy to intravenous contrast for CT imaging eGFR <30 Pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to either the PET/CT arm or the conventional CT arm
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FDG-PET/CT arm<br>Participants with persistent febrile neutropenia after 72 hours of onset who are randomized to this arm will have an FDG-PET/CT performed to look for source of fever. | Diagnostic Test: FDG-PET/CT<br>* FDG-PET performed with low dose CT<br>* Other names: PET/CT;|
| Active Comparator: Conventional CT arm<br>Participants with persistent febrile neutropenia after 72 hours of onset who are randomized to this arm will have a conventional CT (HRCT chest and sinuses +/- other regions as per clinician's discretion) performed to look for source of fever. | Diagnostic Test: Conventional CT<br>* HRCT and CT of sinuses +/- other regions as per clinician's discretion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in management following randomized scan | Defined as: referral for targeted sampling, referral for surgery change in antimicrobial therapy removal of a central line | Within 48 hours of scan result | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with a cause of neutropenic fever | The proportion of participants in each arm where there is a confirmed cause of neutropenic fever | By hospital discharge, an average of 4 weeks | 
| Hospital length of stay | The duration (in days) of hospital length of stay for the episode in which neutropenic fever occurred | By hospital discharge, an average of 4 weeks | 
| Costs of hospital care | The overall cost of the inpatient stay for the episode in which neutropenic fever occurred | By hospital discharge, an average of 4 weeks | 
| Proportion admitted to intensive care | The proportion of patients in each arm who were admitted to intensive care during their admission in which neutropenic fever occurred | By hospital discharge, an average of 4 weeks | 
| In hospital mortality | The proportion of patients per arm who have passed away during the admission in which neutropenic fever occurred | By hospital discharge, an average of 4 weeks | 
| 6 month mortality | The proportion of patients per arm who have passed away 6 months post study entry | 6 months from study entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diagnosis