Clinical trial NCT01114165: Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
Official title: Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hematologic Diseases
Neutropenia
Febrile Neutropenia
Sepsis
Keywords: Neutropenia
Febrile Neutropenia
Sepsis
Polymerase Chain Reaction
Lead sponsor: University Hospital Muenster
Sponsor class: OTHER
Collaborators: name: Pfizer
name: Hoffmann-La Roche
First posted: 2010-05-03
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: The number of changes in empirical antimicrobial therapy
timeFrame: up to the end of study participation
measure: Time to the change to the targeted antimicrobial therapy
timeFrame: at time point of change to the targeted antimicrobial therapy
Secondary outcomes:
measure: 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
timeFrame: at day 1 and 72h after study inclusion
measure: Number of patients having a change to a more appropriate antimicrobial (evaluated retrospectively by susceptibility)
timeFrame: up to the end of study participation
measure: Time to identification of a potential pathogen
timeFrame: at time point of identification of a potential pathogen
measure: Time to change antimicrobial to a more appropriate antimicrobial
timeFrame: at time point of change to a more appropriate antimicrobial
measure: Duration (in days) of antimicrobials
timeFrame: up to the end of study participation
measure: Change in condition severity (clinical parameters)
timeFrame: daily
measure: Days in intensive care unit (ICU)
timeFrame: at the end of study participation
measure: Ventilation duration in ICU (hours)
timeFrame: at the end of study participation
measure: Days in hospital (from study inclusion)
timeFrame: at the end of study participation
measure: All-cause death
timeFrame: at the end of study participation
measure: Treatment costs
timeFrame: up to the end of study participation
Other outcomes:
Locations:
city: Muenster
country: Germany
facility: University Hospital Muenster
state: North Rhine-Westphalia
Study officials:
affiliation: Institute of Medical Microbiology, University Hospital Muenster
name: Karsten Becker, MD, Professor
role: PRINCIPAL_INVESTIGATOR
References: