Clinical trial NCT03876990: Clinical and Medico-economic Evaluation of a Rapid Test (ePlex-BCID®, GenMark) for the Diagnosis of Bacteremia and Fungemia.
Official title: Clinical and Medico-economic Evaluation of a Rapid Test (ePlex-BCID®, GenMark) for the Diagnosis of Bacteremia or Fungemia From Positive Blood Culture Bottles, Combining Fast Identification of Bacteria and Fungi and Evaluation of Bacterial Resistance to First Line Antibiotics.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bacteremia Sepsis
Fungemia
Keywords: multiplex PCR
blood culture
rapid diagnosis
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: GenMark Diagnostics
First posted: 2019-03-15
Enrollment: 312
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized assignation. Half of the patients will be diagnosed by the rapid test in addition to current diagnosis strategy and the other half by current diagnosis strategy alone.
Primary purpose: DIAGNOSTIC

Brief summary: This study evaluates the clinical benefit of a rapid test for fast diagnosis of bacteremia and fungemia from positive blood cultures in case of sepsis. This assay enables rapid identification of bacteria and fungi and allows to evaluate bacterial resistance to first line antibiotics. The clinical and medico-economic impact of this assay used in addition to the current diagnosis strategy (half of the patients) will be compared to the current diagnostic strategy alone (other half of the patient).

Detailed description: Bacteremia and fungemia are severe complications, sometimes life-threatening, of every sepsis. During septicemia, every hour matters to start an appropriate antibiotic or antifungal treatment as every hour of delay is associated to higher death rate.

The rapid multiplex PCR assay that is evaluated in this study allows to identify in 60 to 90 minutes, the bacteria or fungi that is present in the positive blood culture bottles and to identify resistance markers to first line antibiotics that are used to treat sepsis. This strategy allows quicker adaptation of antibacterial or antifungal treatment based on the species of the bacteria or fungi identified and on the results of the resistance markers compared to current diagnosis strategy of bacteremia or fungemia. This quicker adaptation could lead to improved survival rate, reduced complications of sepsis, reduced hospital stay length and could reduce the use of large spectrum antibiotics.

Eligibility criteria: Inclusion Criteria:

* Patient with bacteremia and/or fungemia defined by :

  1/ the presence of clinical signs of sepsis; AND 2/ a positive blood culture, i.e. the growth of at least one species of bacteria or micromyces in at least one blood culture vial
* Patient Hospitalized at Grenoble University Hospital (only North site) and seen by a physician from the antibiotic stewardship team
* First blood culture positive for the patient's sepsis episode
* Informed and written consent signed by the patient or his legal representative or the doctor in case of emergency.

Exclusion Criteria:

* Patients mentioned in the law articles L1121-5 to L1121-8 from French Health Code
* Patients hospitalized in palliative care unit
* Persons with an estimated survival of less than one month

Primary outcomes:
measure: Delay from suspicion of sepsis to optimized antibiotic/antifungal treatment
timeFrame: Follow up is set to hospital length stay with a maximum of 30 days
Secondary outcomes:
measure: Medical evaluation of the consequences of the innovative strategy compared to current strategy : 30-day mortality
timeFrame: Hospital length stay with a maximum of 30 days
measure: Medical evaluation of the consequences of the innovative strategy compared to current strategy : complication rate
timeFrame: Hospital length stay with a maximum of 30 days
measure: Medical evaluation of the consequences of the innovative strategy compared to current strategy : length of hospital stay
timeFrame: Hospital length stay with a maximum of 30 days
measure: Medical evaluation of the consequences of the innovative strategy compared to current strategy : antibiotic treatment duration
timeFrame: Hospital length stay with a maximum of 30 days
measure: Medical evaluation of the consequences of the innovative strategy compared to current strategy : delay of antibiotic/antifungal treatment modification at several time points
timeFrame: Hospital length stay with a maximum of 30 days
measure: Medical evaluation of the consequences of the innovative strategy compared to current strategy : rate of antibiotic/antifungal treatment modification at several time points
timeFrame: Hospital length stay with a maximum of 30 days
measure: Economic evaluation of the hospitalization costs of the innovative strategy compared to current strategy
timeFrame: Hospital length stay with a maximum of 30 days
measure: Economic evaluation of the treatments costs of the innovative strategy compared to current strategy
timeFrame: Hospital length stay with a maximum of 30 days
measure: Economic evaluation of the costs of the innovative compared to current strategy
timeFrame: Hospital length stay with a maximum of 30 days
measure: Economic evaluation of the medical imaging costs of the innovative strategy compared to current strategy
timeFrame: Hospital length stay with a maximum of 30 days
measure: Economic impact of the introduction of the innovative strategy for Grenoble University Hospital
timeFrame: Extrapolation of the costs for a one year period
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Grenoble University Hospital
Study officials:
affiliation: University Hospital, Grenoble
name: Yvan CASPAR, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huang TD, Melnik E, Bogaerts P, Evrard S, Glupczynski Y. Evaluation of the ePlex Blood Culture Identification Panels for Detection of Pathogens in Bloodstream Infections. J Clin Microbiol. 2019 Jan 30;57(2):e01597-18. doi: 10.1128/JCM.01597-18. Print 2019 Feb.
citation: Banerjee R, Teng CB, Cunningham SA, Ihde SM, Steckelberg JM, Moriarty JP, Shah ND, Mandrekar JN, Patel R. Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture Identification and Susceptibility Testing. Clin Infect Dis. 2015 Oct 1;61(7):1071-80. doi: 10.1093/cid/civ447. Epub 2015 Jul 20.
citation: Kumar A, Roberts D, Wood KE, Light B, Parrillo JE, Sharma S, Suppes R, Feinstein D, Zanotti S, Taiberg L, Gurka D, Kumar A, Cheang M. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006 Jun;34(6):1589-96. doi: 10.1097/01.CCM.0000217961.75225.E9.
citation: Patel TS, Kaakeh R, Nagel JL, Newton DW, Stevenson JG. Cost Analysis of Implementing Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry Plus Real-Time Antimicrobial Stewardship Intervention for Bloodstream Infections. J Clin Microbiol. 2016 Dec 28;55(1):60-67. doi: 10.1128/JCM.01452-16. Print 2017 Jan.
citation: Maubon D, Dard C, Garnaud C, Cornet M. Profile of GenMark's ePlex(R) blood culture identification fungal pathogen panel. Expert Rev Mol Diagn. 2018 Feb;18(2):119-132. doi: 10.1080/14737159.2018.1420476. Epub 2017 Dec 28.
citation: Timbrook TT, Morton JB, McConeghy KW, Caffrey AR, Mylonakis E, LaPlante KL. The Effect of Molecular Rapid Diagnostic Testing on Clinical Outcomes in Bloodstream Infections: A Systematic Review and Meta-analysis. Clin Infect Dis. 2017 Jan 1;64(1):15-23. doi: 10.1093/cid/ciw649. Epub 2016 Sep 26.