De-escalation - Antifungal Treatment Immunocompromised Patients (D-ATFIM)

De-escalation of Antifungal Treatment in Immunocompromised Critically Ill Patients With Suspected Invasive Candida Infection: Incidence, Associated Factors, and Safety

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.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Invasive Fungal Disease

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.

• Study Type: Observational
• Enrollment (Anticipated): 296

Contacts and Locations

• Study Contact: Name: Saad Nseir, MD,PhD; Phone Number: +33 03 20 44 44 95; Email: saad.nseir@chru-lille.fr

Study Locations

• France
  • Lille, France, 59000
    • Recruiting
    • CHU Lille
    • Contact: Saad Nseir, MD, PhD; Phone Number: 33320444495; Email: s-nseir@chru-lille.fr
    • Contact: Damia MEDDOUR, CRA; Email: damia.meddour@chru-lille.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with de-escalation of antifungal treatment	De-escalation is defined as a reduction in antifungal treatment spectrum (switch from echinocandines or Amphotericin B to Azoles) or stopping all antifungals within the 5 days following their initiation	5 days following start of antifungal treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Risk factors for de-escalation of antifungal therapy	Clinical characteristics and conditions significantly associated with de-escalation by univariate analysis will be entered in a multiple regression model to determine those independently associated with de-escalation	during the 5 days following start of antifungal
Number of days free of mechanical ventilation	days with no mechanical ventilation	until day 28 after start of antifungal treatment
Number of days free of antifungal treatment	days with no antifungal treatment	until day 28 after start of antifungal treatment
Length of ICU stay	days in the ICU	until day 28 after start of antifungal treatment
All-cause mortality	mortality related to any cause	until day 28 after start of antifungal treatment
Percentage of patients with reoccurrence of candidiasis	reccurrence of candidiasis is defined as a new episode after the end of antifungal treatment	until day 7 after stop of antifungal treatment

Collaborators and Investigators

• Sponsor: University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Actual): January 28, 2019
• Primary Completion (Anticipated): September 1, 2023
• Study Completion (Anticipated): September 1, 2023

Study Registration Dates

• First Submitted: December 3, 2018
• First Submitted That Met QC Criteria: December 11, 2018
• First Posted (Actual): December 12, 2018

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Mortality; Immunocompromised; Intensive care; De-escalation; Antifungal treatment
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Disease Attributes; Bacterial Infections and Mycoses; Mycoses; Critical Illness; Invasive Fungal Infections
• Other Study ID Numbers: 2017_32; 2017-A03113-50 (Other Identifier: ID-RCB number, ANSM)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No