Staphylococcus aureus catheter bloodstream infection
Conditions
Interventions
Trade Name: Xydalba
Product Name: Dalbavancin
Pharmaceutical Form: Powder for concentrate for solution for injection/infusion
Sponsors
CENTRE HOSPITALIER ANNECY GENEVOIS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients aged at least 18 years; 2. Blood cultures positive for S. aureus, obtained within 72 hours before randomization (the date considered is the date of the sampling, not the results); 3. CR-BSI, defined as: One positive blood culture AND Local signs of infection at the catheter site OR at least one positive blood culture obtained from the catheter and the peripheral vein, AND A differential period between catheter versus peripheral blood culture positivity of at least 2h as recommended; AND Same S. aureus isolate (same phenotype) identified from the catheter and the peripheral vein blood cultures; 3. Intravascular catheter – implantable venous access device (port-a-cath and Piccline) – removed before randomization; 4. Informed consent form Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 106
Exclusion criteria
Exclusion criteria: 1. Polymicrobial CR-BSI 2. More than 72 hours of active antibiotic treatment targeting S. aureus (in-vitro susceptibility) administered prior to randomization; 3. Patient with known valvulopathy, previous history of endocarditis, or suspicion of infective endocarditis by physician in charge; 4. Suspicion of any other deep focus infections, such as arthritis, pneumonia, osteomyelitis, or meningitis, presence of cerebral or peripheral emboli (arterial occlusion); 5. Thrombophlebitis 6. Failure to remove any intravascular catheter which was present when first positive blood culture 7. Signs of infection associated with qSOFA score = 2 at randomization 8. Patients with foreign bodies such as: prosthetic heart valve, endovascular prosthesis, ventriculo-atrial shunt, pacemaker, or an automated implantable cardioverter defibrillator (AICD) device 9. Severe liver disease (Child-Pugh C) 10. Severely immunocompromised patients: 11. Contraindication to dalbavancin and/or glycopeptid 12. Life expectancy < 3 months 13. Injection drug user 14. Pregnant or breastfeeding women 15. For premenopausal women: failure to use highly-effective contraceptive methods for 1 month after receiving study drug 16. Participation in other interventional trials within the previous three months or ongoing; 17. Persons held in an institution by legal or official order; 18. Patients under guardianship or curatorship; 19. Patients unable to give a free and informed consent; 20. Patient not affiliated to a social security scheme: obligation of affiliation to a social security scheme or to be a beneficiary.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate, among patients with non-complicated CR-BSIs due to S. aureus, that a single-dose of intravenous (IV) dalbavancin 1500 mg is non-inferior to standard documented antibiotic therapy for 14 days according to national guidelines. ;Secondary Objective: 1. Cure rate at DAY 14 and DAY 90; 2. Mortality rate within 90 days of follow-up; 3. Bloodstream clearance; 4. Patient’s quality of life; 5. Hospitalization length of stay; 6. Cost-utility analyses; 7. Occurrence of any adverse event (AE and SAE), until DAY 90 Exploratory Objectives : 1. Pharmacokinetics of dalbavancin will be performed for all patient randomized in the experimental arm (203 patients) to determine the residual concentration 14 days after dalbavancin injection. 2. Analyses of all strains involved in CR-BSIs included in the trial will be centralized at the French “Centre National de Référence des Staphylocoques”, and will be comprised of determination of susceptibility to dalbavancin of each strain by broth dilution method and strains sero-types and virulence factors. ;Primary end point(s): Clinical cure without relapse at Day 30, defined by the absence of all the following: - Local and/or general signs of infection: o local: redness, induration, swelling, purulent discharge; o general: fever, chills; - Relapse of bacteremia to S. aureus – i.e. a bacteremia due to S. aureus occurring after initial negativation of blood cultures (2 vials); - Any additional antibiotic therapy active on S. aureus received after DAY 14; i.e. between DAY 14 and DAY 30. - Deep focus infection including endocarditis - Death from all causes An independent endpoint committee, blinded to the groups of treatment, will evaluate the primary outcome, thanks to prespecified criteria in the protocol. ;Timepoint(s) of evaluation of this end point: 30 days after randomization | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Clinical cure at DAY 14 and DAY 90 defined by the absence of all the following: For DAY 14 and DAY 90: a. Local and/or general signs of infection: i. local: redness, induration, swelling, purulent discharge; ii. general: fever, chills; b. Relapse of bacteremia to S. aureus – i.e. a bacteremia due to S. aureus occurring after initial negativation of blood cultures (2 vials); c. Any additional antibiotic therapy active on S. aureus received between DAY 14 and DAY 90; 2. Death all-cause occurring within 90 days of follow-up; 3. Time from first positive blood culture to first negative blood cultures (in days), limited to DAY 14 4. Autonomy, pain and anxiety using EQ-5D-5L scale at baseline (Day 0), DAY 14, DAY 30 and DAY 90 5. Hospitalization duration in days; 6. Cost per avoided relapse, life-year gained, and per quality-adjusted life year (QALY); 7. Proportion of patients with any adverse event until DAY 90 ;Timepoint(s) of evaluation of this end point: DAY 14; DAY 30 ; DAY 90 | — |
Countries
France
Contacts
Public ContactMarion NORET
CENTRE HOSPITALIER ANNECY GENEVOIS
Outcome results
None listed