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

• ClinicalTrials.gov Identifier: NCT03774316
• Recruitment Status: Recruiting
• First Posted: December 12, 2018
• Last Update Posted: June 30, 2020
• Sponsor: University Hospital, Lille
• Information provided by (Responsible Party): University Hospital, Lille

Tracking Information

• First Submitted Date: December 3, 2018
• First Posted Date: December 12, 2018
• Last Update Posted Date: June 30, 2020
• Actual Study Start Date: January 28, 2019
• Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 11, 2018)

Percentage of patients with de-escalation of antifungal treatment [ Time Frame: 5 days following start 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 13, 2018)

• Risk factors for de-escalation of antifungal therapy [ Time Frame: during the 5 days following start of antifungal ]
  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
• Number of days free of mechanical ventilation [ Time Frame: until day 28 after start of antifungal treatment ]
  days with no mechanical ventilation
• Number of days free of antifungal treatment [ Time Frame: until day 28 after start of antifungal treatment ]
  days with no antifungal treatment
• Length of ICU stay [ Time Frame: until day 28 after start of antifungal treatment ]
  days in the ICU
• All-cause mortality [ Time Frame: until day 28 after start of antifungal treatment ]
  mortality related to any cause
• Percentage of patients with reoccurrence of candidiasis [ Time Frame: until day 7 after stop of antifungal treatment ]
  reccurrence of candidiasis is defined as a new episode after the end of antifungal treatment

Original Secondary Outcome Measures (submitted: December 11, 2018)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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.

• Detailed Description: This is a 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
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• 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

Condition

• Invasive Fungal Disease
• Critical Illness

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 11, 2018): 296
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 2020
• Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adults immunocompromised patients hospitalized in intensive care units
• Predictable invasive mechanical ventilation duration > 48h
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Saad Nseir, MD,PhD; 03 20 44 44 95 ext +33; saad.nseir@chru-lille.fr

• Listed Location Countries: France

Administrative Information

• NCT Number: NCT03774316
• Other Study ID Numbers: 2017_32; 2017-A03113-50 ( Other Identifier: ID-RCB number, ANSM )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: University Hospital, Lille
• Study Sponsor: University Hospital, Lille
• Collaborators: Not Provided

Investigators

• Principal Investigator: Saad Nseir, MD,PhD; University Hospital, Lille

• PRS Account: University Hospital, Lille
• Verification Date: June 2020