Screening Anti-Fungal Exposure in Intensive Care Units

• Conditions: Antifungal Agents

• Registration Number: NCT03136926
• Lead Sponsor: The University of Queensland

Brief Summary

Adequate antifungal therapy is a critical determinant of survival in patients admitted to an Intensive Care Unit (ICU) with suspected or proven fungal infections. Critical illness can alter the way human body handles antifungal agents, i.e. how the drugs are distributed in the body and removed from the body. Consequently, these changes can increase the risk of inappropriate antifungal exposure that may lead to adverse consequence on patients' outcome. Developing an evidence-based antifungal dosing guideline is of global significance and should be considered a priority to improving clinical outcomes for patients receiving antifungal agents

The aim of the SAFE-ICU Study is to develop optimised antibiotic dosing guidelines for ICU patients with life-threatening infections that account for patient characteristics. This will be achieved through completion of the following aims:

i) Describe detailed demographic, clinical and plasma antibiotic concentration-time data in a large ICU patient cohort; ii) Perform a robust statistical analysis of the data collected in Aim 1 to develop an enhanced preliminary prediction algorithm for antifungal dosing.

This is a multi-national study and will enrol ICU patients who are prescribed an antifungal agent (fluconazole, voriconazole, posaconazole, isavuconazole, caspofungin, anidulafungin, micafungin or amphotericin B). A minimum of 12 patients per drug will be enrolled across at least 15 countries and up to 80 ICUs.

Eligible patients are those admitted to the ICU, who are prescribed an antifungal agent (fluconazole, voriconazole, posaconazole, isavuconazole, caspofungin, anidulafungin, micafungin or amphotericin B). Blood samples will be taken to measure drug concentration. Sampling will occur on two occasions, first during study days 1-3 and then a second time between days 4-7, each over an 8-24 hour period. Blood samples will be taken from a vascular access device already inserted for ICU patient care. Abdominal samples from abdominal indwelling drains already inserted peri operatively will also be collected on these two occasions in the subgroup of patients with intra-abdominal infection. Data on infection, various blood tests and patient specific data will be collected using a structured case report form (CRF). Patients will also be followed up 30 days after enrolment into the study to evaluate 30-day mortality.

Collected samples will be frozen and stored locally and then shipped in large batches for processing at Burns Trauma and Critical Care Research Centre, The University of Queensland, Australia. Data analysis for development of antifungal dosing algorithms will also be undertaken at The University of Queensland, Australia.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01
• Study First Submitted: 2017-04-21
• Study First Submitted QC: 2017-04-26
• Study First Posted: 2017-05-02
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-20
• Last Update Posted: 2018-06-21
• Primary Completion: 2018-09
• Study Completion: 2018-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Age ≥ 18
• Critically ill patients requiring ICU care
• Receiving enteral or intravenous therapy of antifungal of interest (triazole, echinocandin, amphotericin) including prophylaxis indication and antifungal therapy started in another unit (wards, operating room) for the same infectious episode
• Availability of suitable intravenous/intra-arterial access to facilitate sample collection
• Written informed consent has been obtained from the patient or their next of kin (according to local regulatory statements for ethical conduct of research at each study site)

Exclusion Criteria

• Aged < 18 years of age
• Pregnancy
• Consent not obtained (according to local regulatory statements for ethical conduct of research at each study site)
• Diagnosis with human immunodeficiency virus or hepatitis B or C or tuberculosis

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Probability of therapeutic target attainment	Seven days	Probability of attainment of therapeutic target associated with optimal efficacy will be determined by measuring the ratio of area under the concentration-time curve (AUC) to the minimum inhibitory concentration (MIC).

Secondary Outcome Measures

Name	Time	Method
Mortality	30 days	30-day mortality

Trial Locations

Locations (47)

Oschner Medical Center; 🇺🇸 New Orleans, Louisiana, United States

Royal Brisbane and Women's Hospital; 🇦🇺 Brisbane, Queensland, Australia

The Royal Melbourne Hospital; 🇦🇺 Melbourne, Victoria, Australia

Antwerp University Hospital; 🇧🇪 Edegem, Antwerp, Belgium

Uz Brussel; 🇧🇪 Brussels, Belgium

Universitary Saint-Luc hospital; 🇧🇪 Brussels, Belgium

Ghent University hospital; 🇧🇪 Gent, Belgium

UZ Gasthuisberg; 🇧🇪 Leuven, Belgium

CHU de Charleroi site Marie Curie; 🇧🇪 Lodelinsart, Belgium

Chu Ambroise Pare; 🇧🇪 Mons, Belgium

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