Clinical trial NCT03538912: Early Discontinuation of Empirical Antifungal Therapy and Biomarkers
Official title: Impact of the Use of Biomarkers on Early Discontinuation of Empirical Antifungal Therapy in Critically Ill Patients: a Randomized Controlled Study.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Invasive Candidiasis
Keywords: empirical antifungal therapy
invasive candidiasis
biomarkers
de-escalation
ICU
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2018-05-29
Enrollment: 194
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Empirical antifungal therapy (EAT) is frequently prescribed to septic critically ill patients with risk factors for invasive Candida infections (ICI). However, among patients without subsequent proven ICI, antifungal discontinuation is rarely performed, resulting in unnecessary antifungal overuse.

The investigators postulate that the use of fungal biomarkers could increase the percentage of early discontinuation of EAT among critically ill patients suspected of ICI, as compared with a standard strategy, without negative impact on day 28-mortality.

To test this hypothesis, the investigators designed a randomized controlled open-label parallel-group study.

Detailed description: Patients requiring EAT will be randomly assigned to:

* intervention group: a strategy in which EAT duration is determined by (1,3)-B-Dglucan and mannan serum assays, performed on day 0 (day of EAT initiation) and day 3. Early stop recommendation, provided before day 7, will be determined using an algorithm based on the results of biomarkers.
* control group: a routine care strategy, based on international guidelines, which recommend 14 days of treatment for patients without subsequent proven ICI, and who improve under antifungal treatment, or less in other situations.

Eligibility criteria: Inclusion Criteria:

* Patient older than 18 years
* Who require EAT for the first time in the ICU (this treatment is prescribed based on the presence of risk factors and clinical suspicion of ICI)
* With an expected ICU length of stay of at least 6 days after EAT initiation
* Informed written consent

Exclusion Criteria:

* Neutropenia (neutrophil count \<500 cells /µL)
* Active malignant hemopathy
* Bone marrow transplantation in the last 6 months
* Polyvalent immunoglobulins in the past months
* Documented ICI in the past 3 months
* Pregnancy or breastfeeding

Primary outcomes:
measure: percentage of patients receiving early discontinuation of EAT, defined as a discontinuation strictly before day 7 after EAT initiation
timeFrame: day 7 after EAT initiation
Secondary outcomes:
measure: death from any cause
timeFrame: day 28 after EAT initiation
measure: percentage of patients who presented a proven ICI after EAT discontinuation
timeFrame: at day 28 or ICU discharge, if it occurs before day 28
measure: percentage of patients who received at least two periods of antifungal treatment (prescribed for separate episodes of suspected or proven ICI)
timeFrame: at day 28 or ICU discharge, if it occurs before day 28
measure: intensity of Candida colonization during ICU stay
timeFrame: at day 28 or ICU discharge, if it occurs before day 28
measure: percentage of patients colonized with a resistant strain of Candida
timeFrame: at day 28 or ICU discharge, if it occurs before day 28
measure: antifungal-free days
timeFrame: at day 28 or ICU discharge, if it occurs before day 28
measure: ventilator-free days
timeFrame: at day 28 or ICU discharge, if it occurs before day 28
measure: ICU-free days
timeFrame: at day 28 or ICU discharge, if it occurs before day 28
measure: ICU mortality
timeFrame: at day 28 or ICU discharge, if it occurs before day 28
measure: day 90 mortality
timeFrame: at day 90
measure: Characterization of the fungal intestinal microbiota studied by standard mycology
timeFrame: at baseline, at Day 7, day 14 day 21 and day 28
measure: Characterization of the fungal intestinal microbiota studied by metagenomics
timeFrame: at baseline, at Day 7, day 14 day 21 and day 28
measure: Characterization of the bacterial intestinal microbiota studied by culture bacteriology
timeFrame: at baseline, at Day 7, day 14 day 21 and day 28
Other outcomes:
Locations:
city: Arras
country: France
facility: CH ARRAS
city: Douai
country: France
facility: CH de DOUAI
city: Dunkerque
country: France
facility: CH Dunkerque
city: Lens
country: France
facility: Centre Hospitalier Dr Schaffner
city: Lens
country: France
facility: Ch Dr.Schaffner de Lens
city: Lille
country: France
facility: Hôpital Roger Salengro, CHU
city: Roubaix
country: France
facility: CH Roubaix
city: Rouen
country: France
facility: CHU de Rouen
city: Tourcoing
country: France
facility: Ch Tourcoing
city: Valenciennes
country: France
facility: Centre hospitalier de valenciennes
Study officials:
affiliation: University Hospital, Lille
name: Anahita Rouze, MD
role: PRINCIPAL_INVESTIGATOR
References: