Diagnosis of Septicaemia by Detection of Microbial DNA in Blood in Severe Infections - Full Text View

Sponsors and Collaborators:	Assistance Publique - Hôpitaux de Paris Hoffmann-La Roche
Information provided by:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00709358

Purpose

The primary purpose is to improve and quicken the microbial diagnosis in severe infections, since only one third of the cases are documented by blood cultures and adequate anti-infective therapy in the 48 hours reduced mortality and morbidity.

Our hypothesis is that detection of microbial DNA in blood by real time PCR may increase the number of cases diagnosed for bacteraemia or fungemia and shorten the time to positive results, which will provide information for an adequate anti-infectious therapy.

Condition	Intervention	Phase
Febrile Neutropenia Suspicion of Endocarditis Severe Sepsis in Intensive Care Unit	Other: Detection of microbial DNA in blood by SeptiFast® Other: detection of microbial DNA in blood by blood culture	Phase IV

MedlinePlus related topics: Endocarditis Fever Molds Sepsis

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Diagnostic, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Health Economic Evaluation of Rapid Detection of Bacteraemia and Fungemia by Real Time PCR for Cases of Febrile Neutropenia, Suspicion of Endocarditis and Severe Sepsis in Intensive Care Units

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:

Number of bacteraemia and of fungemia - overall - each condition [ Time Frame: max Day 30 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Number of patients with adequate anti-infective therapy [ Time Frame: at day 30 ] [ Designated as safety issue: Yes ]
Adequate anti-infective therapy [ Time Frame: at 24h, 48h, > 48h ] [ Designated as safety issue: Yes ]
Time between sampling for microbial investigation and positive results relevant for the diagnosis [ Time Frame: between sampling for microbial investigation and positive results ] [ Designated as safety issue: Yes ]
Mortality [ Time Frame: at Day 30 ] [ Designated as safety issue: Yes ]
Sepsis chock, secondary infectious focus [ Time Frame: at Day 30 ] [ Designated as safety issue: Yes ]
For neutropenia cases, number of patients who evaluated with a clinical focus of infection [ Time Frame: at day 30 ] [ Designated as safety issue: Yes ]
Diagnosis of endocarditis [ Time Frame: at Day 45 ] [ Designated as safety issue: Yes ]
Number of non clinical investigations (microbial and non microbial) [ Time Frame: at day 30 ] [ Designated as safety issue: Yes ]
Length of hospital stay [ Time Frame: at day 30 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	2000
Study Start Date:	May 2008
Estimated Study Completion Date:	March 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
2: Active Comparator Detection by blood culture	Other: detection of microbial DNA in blood by blood culture A blood culture is a test to find an infection in the blood. Most bacteria can be seen in the culture in 2 to 3 days, but some types can take 10 days or longer to show up. Fungus can take up to 30 days to show up in the culture.
1: Experimental Test LightCycler SeptiFast® (Roche)	Other: Detection of microbial DNA in blood by SeptiFast® The LightCycler® SeptiFast Test, the innovative real-time PCR test from Roche Diagnostics, is designed to detect and identify the 25 most important bacterial and fungal species causing bloodstream infections within just a few hours. The LightCycler® SeptiFast Test detects the pathogenic bacteria and fungi directly from whole blood without the need for prior incubation or culture steps. Rapid detection and identification of bacterial and fungal DNA, directly from a 1.5 ml whole blood sample, without prior incubation or culture steps in less than 6 hours.

Arms

Assigned Interventions

2: Active Comparator

Detection by blood culture

Other: detection of microbial DNA in blood by blood culture

A blood culture is a test to find an infection in the blood. Most bacteria can be seen in the culture in 2 to 3 days, but some types can take 10 days or longer to show up. Fungus can take up to 30 days to show up in the culture.

1: Experimental

Test LightCycler SeptiFast® (Roche)

Other: Detection of microbial DNA in blood by SeptiFast®

The LightCycler® SeptiFast Test, the innovative real-time PCR test from Roche Diagnostics, is designed to detect and identify the 25 most important bacterial and fungal species causing bloodstream infections within just a few hours. The LightCycler® SeptiFast Test detects the pathogenic bacteria and fungi directly from whole blood without the need for prior incubation or culture steps.

Rapid detection and identification of bacterial and fungal DNA, directly from a 1.5 ml whole blood sample, without prior incubation or culture steps in less than 6 hours.

Detailed Description:

We will evaluate the advantage of adding the molecular test to the microbial investigations usually done (blood cultures and others) in cases of febrile neutropenia, suspicion of infective endocarditis and severe sepsis in intensive care units.

This is a prospective study conducted in 18 sites (7 in the Paris area and 11 all over France) which will enrolled about 2000 patients over 18 years. Sites are randomized for starting with a 6-month period performing the test or 6-month period without the test (control time with the standard of care).

Primary outcome are the number of patients with documented bacteraemia or fungemia. Secondary outcome are (1) the number of patients with an adequate anti-infective therapy and how long it happens after the diagnosis, (2) mortality, (3) new complicated infection, (4) number of investigations (microbial and non microbial) done for the etiological diagnosis, and global hospitalization costs.

The advantage of the new test will be evaluated per protocol and with an intend to treat analyses. We hypothesized that the new test will bring 15% more microbial diagnosis than the standard of care. Consequently, and according to the number of sites interested in the study, 166 to 2500 patients will be enrolled with 480 to 750 patients with febrile neutropenia, 1000 to 1500 patients with severe sepsis in Intensive Care Units (ICU). Patients with suspicion of infective endocarditis will be evaluated for the number of diagnosis of true endocarditis according to Duke Criteria, and the time to diagnosis.

Health economic evaluation will compare the costs of hospitalization, microbial investigations including the new test, other non clinical investigations and consequences on the organization.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age≥ 18 years
Written signed and dated inform consent
First time with fever observed in a neutropenic patient
Severe sepsis in a patient hospitalized in ICU
Suspicion of infective endocarditis
Microbial investigation from Monday to Friday

Exclusion Criteria:

Not affiliated to Health Insurance (social security)
Included in another interventional trial testing microbial DNA detection during the time "without Septifast®"
Included in another clinical trial for which the clinician assumes that it will not be possible to prescribe an anti-infectious therapy adequately to microbial detection in the blood
Patient previously included in the protocol
Sepsis with a microbial diagnosis

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00709358

Contacts

Contact: Emmanuelle CAMBAU, PH	1 49 81 28 31 ext +33	emmanuelle.cambau@hmn.aphp.fr
Contact: Mabel GABA	1 49 81 37 98 ext +33	mabel.gaba@hmn.aphp.fr

Locations

France
CHU Henri Mondor	Recruiting
Créteil, France
Contact: Emmanuelle CAMBAU, PH 1 49 81 28 31 ext +33 emmanuelle.cambau@hmn.aphp.fr
Contact: René COURCOL, PH 3 20 44 49 08 ext +33 rcourcol@chru-lille.fr
Principal Investigator: Emmanuelle CAMBAU, PH

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Hoffmann-La Roche

Investigators

Principal Investigator:	Emmanuelle CAMBAU, PH	Assistance Publique - Hôpitaux de Paris
Principal Investigator:	René COURCOL, PH	CHRU LILLE

More Information

Responsible Party:	Department Clinical Research of Developpement ( Magali LAFAYE )
Study ID Numbers:	P070308
Study First Received:	July 2, 2008
Last Updated:	November 24, 2008
ClinicalTrials.gov Identifier:	NCT00709358
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

bacteria
fungi
real time PCR

adequate antimicrobial therapy
microbial DNA
microbial diagnosis

Study placed in the following topic categories:

Systemic Inflammatory Response Syndrome
Heart Diseases
Hematologic Diseases
Agranulocytosis
Bacteremia
Leukocyte Disorders
Granulocytopenia

Endocarditis
Inflammation
Fever
Neutropenia
Sepsis
Fungemia
Leukopenia

Additional relevant MeSH terms:

Pathologic Processes
Cardiovascular Diseases
Infection

ClinicalTrials.gov processed this record on January 14, 2009