Screening Anti-Fungal Exposure in Intensive Care Units

Study Overview
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Brief Summary
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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.

Official Title
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An International, Multi-centre Prospective Pharmacokinetic Evaluation of Antifungal Drug Exposure in Intensive Care Unit Patients Receiving Conventional Dosing Regimens

Conditions
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Antifungal Agents

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of therapeutic target attainment | 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). | Seven days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | 30-day mortality | 30 days |