CANDIDEMIA
Conditions
Brief summary
Scientific justification Candidemia is a major public health problem. In France, the 30-day mortality of candidemia varies from 30% to 50% depending on the need for intensive care and it has not decreased in 30 years. The duration of treatment for candidemia was set at a minimum of 14 days after the last positive blood culture following the Rex trial (1) comparing the efficacy of fluconazole vs amphotericin B where the minimum duration of treatment was imposed. The risk of a too short treatment is the absence of control of the candidemia with secondary dissemination, in particular cardiac and ophthalmic. A retrospective study looking at the risk of ophthalmologic complications after candidemia found among the 21/78 treated for less than 14 days, only one case of late endophthalmitis in a patient who had only been treated for 48 hours. In addition, the prolonged duration of antifungals exposes the risk of selection of more resistant strains with a modification of the flora, with the possibility of acquiring resistance as early as 8 days of treatment with caspofungin, and has a greater liver toxicity. There is no prospective study on the direct impact of antifungal agents (type of antifungal agent and duration) on the mycobiota.
Interventions
DRUGStandard of Care (SOC)
14 days of antifungal therapy after the 1st negative blood culture
DRUGShortened duration of antifungal therapy
7 days of antifungal therapy after the 1st negative blood culture
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Design of the study Multicenter, controlled, randomized, non-inferiority, clinical trial with 2 parallel groups (1:1)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults (Age ≥ 18 years old) * With an uncomplicated candidemia defined by the absence of secondary sites requiring prolonged treatment: endocarditis, ophthalmologic involvement, thrombosed catheter, arthritis, meningitis, candida abscess that cannot be drained, pyelonephritis. * Without expected aplasia duration greater than 7 days * Being apyretic and having a 1st negative blood culture after diagnosis * Removal of the vascular catheter if present * Written informed consent from the patients or his/her relatives * Patients with less than 7 days of aplasia predictable
Exclusion criteria
* Presence of an indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained and is likely to be the source of candidemia or the presence of secondary sites of candidemia requiring prolonged treatment * Patients with more than 7 days of aplasia * Candida strain resistant to the antifungal used * Pregnancy, breastfeeding * Hypersensitivity or previous severe adverse drug reaction to the antifungal treatments. * unwilling, in the judgment of the investigator, to comply with the protocol * Patient under legal guardianship or without healthcare coverage * Women with childbearing potential not using adequate contraception
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-cause mortality (ACM) | At day 28 | at day 28 after the 1st negative blood culture under antifungal treatment for all patients included with an uncomplicated candidemia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative incidence of death related to fungal infection | At day 28 | at Day 28 after the 1st negative blood culture under antifungal treatment |
| Aspartate Amino-transferase level | At day 14 | — |
| alanine aminotransférase (ALAT) level | At day 14 | — |
| Proportion of patients with secondary localizations | At day 28 | — |
| Bilirubin blood levels | At day 14 | — |
| Cost per extra-day alive without antifungal treatment | Up to day 28 | Incremental cost effectiveness ratio |
| Gamma-Glutamyl Transférase (GGT) level | At day 14 | — |
Contacts
Primary ContactBlandine Denis, MD
Backup ContactJérôme Lambert, MD PhD
Outcome results
None listed