Early Discontinuation of Empirical Antifungal Therapy and Biomarkers - Clinical Trial for Invasive Candidiasis | NCT03538912

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Primary Purpose

Status

Recruiting

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Biomarker strategy

Routine strategy

About this trial

This is an interventional treatment trial for Invasive Candidiasis focused on measuring empirical antifungal therapy, invasive candidiasis, biomarkers, de-escalation, ICU

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Biomarker group

Routine group

Arm Description

patient follow the Biomarker strategy

patient follow the routine strategy

Outcomes

Primary Outcome Measures

percentage of patients receiving early discontinuation of EAT, defined as a discontinuation strictly before 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: superior in terms of antifungal use and Non-inferior in terms of death

Secondary Outcome Measures

death from any cause

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: superior in terms of antifungal use and Non-inferior in terms of death

percentage of patients who presented a proven ICI after EAT discontinuation

percentage of patients who received at least two periods of antifungal treatment (prescribed for separate episodes of suspected or proven ICI)

intensity of Candida colonization during ICU stay

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.

percentage of patients colonized with a resistant strain of Candida

antifungal-free days

ventilator-free days

ICU-free days

ICU mortality

day 90 mortality

Characterization of the fungal intestinal microbiota studied by standard mycology

Characterization of the fungal intestinal microbiota studied by metagenomics

Characterization of the bacterial intestinal microbiota studied by culture bacteriology

Full Information

NCT ID

NCT03538912

First Posted

April 25, 2018

Last Updated

August 18, 2022

Sponsor

University Hospital, Lille

1. Study Identification

Unique Protocol Identification Number

NCT03538912

Brief Title

Early Discontinuation of Empirical Antifungal Therapy and Biomarkers

Acronym

SEAT

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

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Recruiting

Study Start Date

June 6, 2018 (Actual)

Primary Completion Date

May 2023 (Anticipated)

Study Completion Date

May 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Lille

4. Oversight

Studies a U.S. FDA-regulated Drug Product

No

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Invasive Candidiasis

Keywords

empirical antifungal therapy, invasive candidiasis, biomarkers, de-escalation, ICU

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

194 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Biomarker group

Arm Type

Other

Arm Description

patient follow the Biomarker strategy

Arm Title

Routine group

Arm Type

Other

Arm Description

patient follow the routine strategy

Intervention Type

Other

Intervention Name(s)

Biomarker strategy

Intervention Description

EAT duration is determined by β-D-1,3-glucan and mannan serum assays, performed at day 0 (day of EAT initiation) and day 3.

Intervention Type

Other

Intervention Name(s)

Routine strategy

Intervention Description

EAT duration is based on IDSA guidelines, which recommend 14 days of treatment for patients without subsequent proven ICI, and who improve under antifungal treatment, or less in other situations.

Primary Outcome Measure Information:

Title

percentage of patients receiving early discontinuation of EAT, defined as a discontinuation strictly before day 7 after EAT initiation

Description

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: superior in terms of antifungal use and Non-inferior in terms of death

Time Frame

day 7 after EAT initiation

Secondary Outcome Measure Information:

Title

death from any cause

Description

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: superior in terms of antifungal use and Non-inferior in terms of death

Time Frame

day 28 after EAT initiation

Title

percentage of patients who presented a proven ICI after EAT discontinuation

Time Frame