Febrile Neutropenia, Hematologic Diseases, Neutropenia, Sepsis
Conditions
Keywords
Neutropenia, Febrile Neutropenia, Sepsis, Polymerase Chain Reaction
Brief summary
The overall objective of this study is to assess the clinical value of the SeptiFast Test as an adjunct to traditional microbiological, clinical, and other laboratory assessments in early detection and identification of a potential pathogen and therefore early targeted antimicrobial management of neutropenic hematological patients with suspected infection or sepsis.
Detailed description
Infections, including sepsis, continue to be a major cause of morbidity and mortality in patients with hematologic diseases. Early diagnosis of infection, rapid identification of the causative pathogen(s), and prompt initiation of appropriate antimicrobial treatment (the first 24 hours are most critical) all have a major impact on mortality. The LightCycler® SeptiFast Test MGRADE (SeptiFast Test) is an in vitro nucleic acid amplification test for the direct detection and identification of DNA from bacterial and fungal microorganisms in human EDTA whole blood. The SeptiFast test can detect nucleic acids from the most common pathogens (approximately 90%) responsible for hospital-associated bacteremia. The test is used in conjunction with the patient's clinical presentation and established microbiological assays and other laboratory markers as an aid in antimicrobial treatment decision making for patients with suspected sepsis and other bloodstream infections. This is a randomized prospective study of the use of the SeptiFast Test as an adjunct to traditional management of neutropenic haematological patients suspected of having infection or sepsis. The study will be performed in a two-armed manner. The blood sample for the SeptiFast Test will be collected from all included patients. However, analysis of the SeptiFast Test in the control group will only be performed at a later point in time; thus, in the control group results will not become available until the end of the study and, therefore, cannot be used for guiding clinical decisions. Patients complete the study when the episode of infection or sepsis resolves, or the patient is discharged from a hospital, or the patient died.
Interventions
OTHERDetection of microbial DNA in blood by SeptiFast Test
The SeptiFast Test is a multiplex polymerase chain reaction (PCR) test that can detect nucleic acids from the most common pathogens (approximately 90%) responsible for hospital-associated bacteremia and takes approx. 6 hours to perform
OTHERPathogen detection by blood culture
Blood culture is a conventional microbiological method of pathogen detection. Results from blood cultures are usually not available until 24 to 72 hours after sampling
Sponsors
Pfizer
Hoffmann-La Roche
University Hospital Muenster
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient with hematological disease and neutropenia \< 500/µl (or \< 1000/µl, if criterion 5A is fulfilled) 2. Known or acute infection, or suspected infection, or sepsis, which clinically indicates investigation by blood culture 3. Time-frame after diagnosis or suspicion of infection or sepsis: \< 72 hours 4. Species causing infection not known before inclusion 5. Patient fulfils criterion A or/and B A. Indication for an initiation of antimicrobial therapy in patients with febrile neutropenia * Neutropenia \<500/µl or \<1000/µl if decline to \<500/µl is expected in the next 48h. * Single (oral) temperature of ≥ 38.3°C, or temperature ≥ 38.0°C lasting for at least 1h or measured twice within 12h. * No evidence of non-infectious cause of fever (blood products, drugs reactions, etc) B. At least two of the following criteria: * Temperature \>38°C or \<36°C * Heart rate \>90 beats/minute * Respiratory rate \>20 breaths/minute or PaCO2 \<32 mmHg / 4,3 kPa 6. Patient is able to provide written informed consent
Exclusion criteria
1. Moribund patients with survival expectation \< 24h 2. Younger than 18 years 3. Patient is not able to provide informed consent 4. Patients not suitable for study participation in the opinion of investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The number of changes in empirical antimicrobial therapy | up to the end of study participation |
| Time to the change to the targeted antimicrobial therapy | at time point of change to the targeted antimicrobial therapy |
Secondary
| Measure | Time frame |
|---|---|
| Time to identification of a potential pathogen | at time point of identification of a potential pathogen |
| Time to change antimicrobial to a more appropriate antimicrobial | at time point of change to a more appropriate antimicrobial |
| Duration (in days) of antimicrobials | up to the end of study participation |
| Change in condition severity (clinical parameters) | daily |
| The number of patients with a potential pathogen identified by the SeptiFast Test, compared with the number of patients likely to have bloodstream infection or sepsis, as determined by a constructed clinical comparator | at day 1 and 72h after study inclusion |
| Ventilation duration in ICU (hours) | at the end of study participation |
| Days in hospital (from study inclusion) | at the end of study participation |
| All-cause death | at the end of study participation |
| Treatment costs | up to the end of study participation |
| Days in intensive care unit (ICU) | at the end of study participation |
| Number of patients having a change to a more appropriate antimicrobial (evaluated retrospectively by susceptibility) | up to the end of study participation |
Countries
Germany
Outcome results
None listed