Early Discontinuation of Empirical Antifungal Therapy and Biomarkers
- Conditions
- Invasive Candidiasis
- Interventions
- Other: Routine strategyOther: Biomarker strategy
- Registration Number
- NCT03538912
- Lead Sponsor
- University Hospital, Lille
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 194
- 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
- Neutropenia (neutrophil count <500 cells /Β΅L)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Routine group Routine strategy patient follow the routine strategy Biomarker group Biomarker strategy patient follow the Biomarker strategy
- Primary Outcome Measures
Name Time Method percentage of patients receiving early discontinuation of EAT, defined as a discontinuation strictly before day 7 after EAT initiation day 7 after EAT initiation This trial is designed to demonstrate whether, in critically ill patients suspected for ICI, the biomarker strategy, as compared with a standard strategy, is at the same time:
1. superior in terms of antifungal use and
2. Non-inferior in terms of death
- Secondary Outcome Measures
Name Time Method death from any cause day 28 after EAT initiation This trial is designed to demonstrate whether, in critically ill patients suspected for ICI, the biomarker strategy, as compared with a standard strategy, is at the same time:
1. superior in terms of antifungal use and
2. Non-inferior in terms of deathpercentage of patients colonized with a resistant strain of Candida at day 28 or ICU discharge, if it occurs before day 28 percentage of patients who presented a proven ICI after EAT discontinuation at day 28 or ICU discharge, if it occurs before day 28 percentage of patients who received at least two periods of antifungal treatment (prescribed for separate episodes of suspected or proven ICI) at day 28 or ICU discharge, if it occurs before day 28 intensity of Candida colonization during ICU stay at day 28 or ICU discharge, if it occurs before day 28 Five body sites (among urine, anal swabs, pharyngeal swabs, nasal swabs, axillary swabs, gastric aspirates if patients have a nasogastric tube, and tracheal aspirates if patients are intubated or have a tracheotomy) are sampled on day 0 and then once per week for the semi-quantitative determination of yeast colonisation. The number of colony-forming units is scored as follows: score 1, \<10 colony-forming units; score 2, 10 to 50 colony-forming units; score 3, \>50 colony-forming units; score 4, \>50 colony-forming units confluent. Intensity of colonization is determined for each date of sampling, by dividing the sum score for each colonized site by the number of sites sampled giving a mean Candida load. An overall score of \>4 is possible in the case of isolation of several Candida species.
antifungal-free days at day 28 or ICU discharge, if it occurs before day 28 ventilator-free days at day 28 or ICU discharge, if it occurs before day 28 ICU-free days at day 28 or ICU discharge, if it occurs before day 28 ICU mortality at day 28 or ICU discharge, if it occurs before day 28 day 90 mortality at day 90 Characterization of the fungal intestinal microbiota studied by standard mycology at baseline, at Day 7, day 14 day 21 and day 28 Characterization of the fungal intestinal microbiota studied by metagenomics at baseline, at Day 7, day 14 day 21 and day 28 Characterization of the bacterial intestinal microbiota studied by culture bacteriology at baseline, at Day 7, day 14 day 21 and day 28
Trial Locations
- Locations (10)
CHU de Rouen
π«π·Rouen, France
Centre hospitalier de valenciennes
π«π·Valenciennes, France
CH Dunkerque
π«π·Dunkerque, France
CH ARRAS
π«π·Arras, France
CH de DOUAI
π«π·Douai, France
Centre Hospitalier Dr Schaffner
π«π·Lens, France
HΓ΄pital Roger Salengro, CHU
π«π·Lille, France
Ch Dr.Schaffner de Lens
π«π·Lens, France
CH Roubaix
π«π·Roubaix, France
Ch Tourcoing
π«π·Tourcoing, France