Clinical trial NCT00709358: Diagnosis of Septicaemia by Detection of Microbial DNA in Blood in Severe Infections
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Febrile Neutropenia
Endocarditis
Severe Sepsis
Keywords: bacteria
fungi
real time PCR
adequate antimicrobial therapy
microbial DNA
microbial diagnosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Hoffmann-La Roche
First posted: 2008-07-03
Enrollment: 2000
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 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.

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 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

Primary outcomes:
measure: Number of bacteraemia and of fungemia - overall - each condition
timeFrame: max Day 30
Secondary outcomes:
measure: Number of patients with adequate anti-infective therapy
timeFrame: at day 30
measure: Adequate anti-infective therapy
timeFrame: at 24h, 48h, > 48h
measure: Time between sampling for microbial investigation and positive results relevant for the diagnosis
timeFrame: between sampling for microbial investigation and positive results
measure: Mortality
timeFrame: at Day 30
measure: Sepsis chock, secondary infectious focus
timeFrame: at Day 30
measure: For neutropenia cases, number of patients who evaluated with a clinical focus of infection
timeFrame: at day 30
measure: Diagnosis of endocarditis
timeFrame: at Day 45
measure: Number of non clinical investigations (microbial and non microbial)
timeFrame: at day 30
measure: Length of hospital stay
timeFrame: at day 30
Other outcomes:
Locations:
city: Créteil
country: France
facility: CHU Henri Mondor
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Emmanuelle CAMBAU, PH
role: PRINCIPAL_INVESTIGATOR
affiliation: CHRU LILLE
name: René COURCOL, PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cambau E, Durand-Zaleski I, Bretagne S, Brun-Buisson C, Cordonnier C, Duval X, Herwegh S, Pottecher J, Courcol R, Bastuji-Garin S; EVAMICA study team. Performance and economic evaluation of the molecular detection of pathogens for patients with severe infections: the EVAMICA open-label, cluster-randomised, interventional crossover trial. Intensive Care Med. 2017 Nov;43(11):1613-1625. doi: 10.1007/s00134-017-4766-4. Epub 2017 Apr 3.