Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients

• ClinicalTrials.gov Identifier: NCT01114165
• Recruitment Status: Completed
• First Posted: May 3, 2010
• Last Update Posted: December 5, 2012
• Sponsor: University Hospital Muenster
• Collaborators: Pfizer; Hoffmann-La Roche
• Information provided by (Responsible Party): University Hospital Muenster

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hematologic Diseases; Neutropenia; Febrile Neutropenia; Sepsis	Other: Detection of microbial DNA in blood by SeptiFast Test; Other: Pathogen detection by blood culture	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Value of the LightCycler® SeptiFast Test MGRADE for the Pathogen Detection in Neutropenic Hematological Patients
• Study Start Date: May 2010
• Actual Primary Completion Date: September 2012
• Actual Study Completion Date: September 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: SeptiFast Test; Pathogen detection by SeptiFast Test as an adjunct to traditional microbiological assessments including blood culture	Other: Detection 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
Active Comparator: Only Conventional Diagnostics; Pathogen detection only by conventional microbiological assessments, e.g. blood culture	Other: Pathogen 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

Outcome Measures

Primary Outcome Measures :

1. The number of changes in empirical antimicrobial therapy [ Time Frame: up to the end of study participation ]
2. Time to the change to the targeted antimicrobial therapy [ Time Frame: at time point of change to the targeted antimicrobial therapy ]

Secondary Outcome Measures :

1. 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 [ Time Frame: at day 1 and 72h after study inclusion ]
2. Number of patients having a change to a more appropriate antimicrobial (evaluated retrospectively by susceptibility) [ Time Frame: up to the end of study participation ]
3. Time to identification of a potential pathogen [ Time Frame: at time point of identification of a potential pathogen ]
4. Time to change antimicrobial to a more appropriate antimicrobial [ Time Frame: at time point of change to a more appropriate antimicrobial ]
5. Duration (in days) of antimicrobials [ Time Frame: up to the end of study participation ]
6. Change in condition severity (clinical parameters) [ Time Frame: daily ]
7. Days in intensive care unit (ICU) [ Time Frame: at the end of study participation ]
8. Ventilation duration in ICU (hours) [ Time Frame: at the end of study participation ]
9. Days in hospital (from study inclusion) [ Time Frame: at the end of study participation ]
10. All-cause death [ Time Frame: at the end of study participation ]
11. Treatment costs [ Time Frame: up to the end of study participation ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Germany

University Hospital Muenster

Muenster, North Rhine-Westphalia, Germany, 48149

Sponsors and Collaborators

University Hospital Muenster

Pfizer

Hoffmann-La Roche

Investigators

• Principal Investigator: Karsten Becker, MD, Professor; Institute of Medical Microbiology, University Hospital Muenster

More Information

• Responsible Party: University Hospital Muenster
• ClinicalTrials.gov Identifier: NCT01114165
• Other Study ID Numbers: UKM-SF-042010
• First Posted: May 3, 2010
• Last Update Posted: December 5, 2012
• Last Verified: November 2012

Keywords provided by University Hospital Muenster:

Neutropenia; Febrile Neutropenia; Sepsis; Polymerase Chain Reaction

Additional relevant MeSH terms:

Neutropenia; Hematologic Diseases; Febrile Neutropenia; Agranulocytosis; Leukopenia; Leukocyte Disorders