Clinical trial NCT03774316: De-escalation - Antifungal Treatment Immunocompromised Patients
Official title: De-escalation of Antifungal Treatment in Immunocompromised Critically Ill Patients With Suspected Invasive Candida Infection: Incidence, Associated Factors, and Safety
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Invasive Fungal Disease
Critical Illness
Keywords: De-escalation
Antifungal treatment
Mortality
Immunocompromised
Intensive care
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2018-12-12
Enrollment: 296
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adults immunocompromised patients hospitalized in intensive care units (Age ≥18 years)

Immunosuppression is defined by:

* long-term immunosuppressive therapy (\> 3 months) or high-dose corticosteroid therapy (\> 0.5 mg / kg / day for at least 3 days)
* Solid organ transplant
* Solid cancer (active or in remission since \<5 years)
* Malignant haemopathy
* HIV infection with CD4 \<200

Brief summary: A small proportion of intensive care unit patients receiving antifungals have a proven invasive fungal infection. However, antifungal treatment has side effects such as toxicity, emergence of resistance, and high cost. Moreover, empirical antifungal treatment is still a matter for debate in these patients. Our study aimed to determine the incidence, associated factors, and safety of de-escalation of antifungals in immunocompromised critically ill patients.

This prospective observational study is conducted in 14 ICU, during a 6 months period. All immunocompromised patients hospitalized for \>5d and treated with antifungals for suspected or proven invasive candida infection will be included De-escalation is defined as a reduction in antifungal spectrum or stopping initial drugs within the 5 days following their initiation. The three antifungals considered in this study are from the narrowest to the widest spectrum: fluconazole, caspofungin and liposomal amphotericin B.

Detailed description: This is a retrospective and prospective observational multicenter study, aiming to determine the incidence, and safety of antifungal de-escalation in immunocompromised patients, and also factors associated with de-escalation.

Eligibility criteria: Inclusion Criteria:

* Adults immunocompromised patients hospitalized in intensive care units
* Predictable invasive mechanical ventilation duration \> 96h
* Signed consent (by patient or its representative)
* First antifungal treatment initiation in ICU for proven or suspected candida infection

Exclusion Criteria:

* Pregnant or breast-feeding women.
* Fungal infection other than invasive candida
* Prophylactic antifungal treatment.
* Lack of informed consent
* Predictable mechanical ventilation duration less than 48 hours
* Patients discharged from ICU before the 5th day after initiation of TAF

Primary outcomes:
measure: Percentage of patients with de-escalation of antifungal treatment
timeFrame: 5 days following start of antifungal treatment
Secondary outcomes:
measure: Risk factors for de-escalation of antifungal therapy
timeFrame: during the 5 days following start of antifungal
measure: Number of days free of mechanical ventilation
timeFrame: until day 28 after start of antifungal treatment
measure: Number of days free of antifungal treatment
timeFrame: until day 28 after start of antifungal treatment
measure: Length of ICU stay
timeFrame: until day 28 after start of antifungal treatment
measure: All-cause mortality
timeFrame: until day 28 after start of antifungal treatment
measure: Percentage of patients with reoccurrence of candidiasis
timeFrame: until day 7 after stop of antifungal treatment
Other outcomes:
Locations:
city: Lille
country: France
facility: CHU Lille
Study officials:
affiliation: University Hospital, Lille
name: Saad Nseir, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: