Early Discontinuation of Empirical Antifungal Therapy and Biomarkers (SEAT)

August 18, 2022 updated by: University Hospital, Lille

Impact of the Use of Biomarkers on Early Discontinuation of Empirical Antifungal Therapy in Critically Ill Patients: a Randomized Controlled Study.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

194

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Arras, France
        • Recruiting
        • CH Arras
      • Douai, France
        • Recruiting
        • CH de Douai
      • Dunkerque, France
        • Recruiting
        • Ch Dunkerque
      • Lens, France
        • Recruiting
        • Centre Hospitalier Dr Schaffner
      • Lens, France
        • Recruiting
        • Ch Dr.Schaffner de Lens
      • Lille, France
        • Recruiting
        • Hôpital Roger Salengro, CHU
      • Roubaix, France
        • Recruiting
        • CH Roubaix
        • Principal Investigator:
          • Martine NYUNGA MAKENGA, MD
      • Rouen, France
        • Recruiting
        • CHU de Rouen
      • Tourcoing, France
        • Recruiting
        • Ch Tourcoing
      • Valenciennes, France
        • Recruiting
        • Centre Hospitalier de Valenciennes
        • Principal Investigator:
          • Isabelle ALVES, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Biomarker group
patient follow the Biomarker strategy
Other: Biomarker strategy
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.
Other: Routine group
patient follow the routine strategy
Other: Routine strategy
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
percentage of patients receiving early discontinuation of EAT, defined as a discontinuation strictly before day 7 after EAT initiation
Time Frame: 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
day 7 after EAT initiation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
death from any cause
Time Frame: 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 death
day 28 after EAT initiation
percentage of patients who presented a proven ICI after EAT discontinuation
Time Frame: at day 28 or ICU discharge, if it occurs before day 28
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)
Time Frame: at day 28 or ICU discharge, if it occurs before day 28
at day 28 or ICU discharge, if it occurs before day 28
intensity of Candida colonization during ICU stay
Time Frame: 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.
at day 28 or ICU discharge, if it occurs before day 28
percentage of patients colonized with a resistant strain of Candida
Time Frame: at day 28 or ICU discharge, if it occurs before day 28
at day 28 or ICU discharge, if it occurs before day 28
antifungal-free days
Time Frame: at day 28 or ICU discharge, if it occurs before day 28
at day 28 or ICU discharge, if it occurs before day 28
ventilator-free days
Time Frame: at day 28 or ICU discharge, if it occurs before day 28
at day 28 or ICU discharge, if it occurs before day 28
ICU-free days
Time Frame: at day 28 or ICU discharge, if it occurs before day 28
at day 28 or ICU discharge, if it occurs before day 28
ICU mortality
Time Frame: at day 28 or ICU discharge, if it occurs before day 28
at day 28 or ICU discharge, if it occurs before day 28
day 90 mortality
Time Frame: at day 90
at day 90
Characterization of the fungal intestinal microbiota studied by standard mycology
Time Frame: at baseline, at Day 7, day 14 day 21 and day 28
at baseline, at Day 7, day 14 day 21 and day 28
Characterization of the fungal intestinal microbiota studied by metagenomics
Time Frame: at baseline, at Day 7, day 14 day 21 and day 28
at baseline, at Day 7, day 14 day 21 and day 28
Characterization of the bacterial intestinal microbiota studied by culture bacteriology
Time Frame: at baseline, at Day 7, day 14 day 21 and day 28
at baseline, at Day 7, day 14 day 21 and day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Lille

Investigators

  • Principal Investigator: Anahita Rouze, MD, University Hospital, Lille

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 6, 2018

Primary Completion (Anticipated)

May 1, 2023

Study Completion (Anticipated)

May 1, 2023

Study Registration Dates

First Submitted

April 25, 2018

First Submitted That Met QC Criteria

May 24, 2018

First Posted (Actual)

May 29, 2018

Study Record Updates

Last Update Posted (Actual)

August 22, 2022

Last Update Submitted That Met QC Criteria

August 18, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2017_07
  • 2017-003793-13 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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