Clinical trial NCT03136926: Screening Anti-Fungal Exposure in Intensive Care Units
Official title: An International, Multi-centre Prospective Pharmacokinetic Evaluation of Antifungal Drug Exposure in Intensive Care Unit Patients Receiving Conventional Dosing Regimens
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Antifungal Agents
Lead sponsor: The University of Queensland
Sponsor class: OTHER
First posted: 2017-05-02
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will comprise adult critically ill patients (≥18 years) requiring ICU care, including both surgical and medical ICU patients. Representation of the study population will be ensured by enrolling all patients at the study sites who meet the study criteria during the study period. The study will recruit patients prescribed to receive any of the chosen systemic antifungal agents regardless of whether prescribed for treatment, pre-emptive treatment or for prophylaxis.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Probability of therapeutic target attainment
timeFrame: Seven days
Secondary outcomes:
measure: Mortality
timeFrame: 30 days
Other outcomes:
Locations:
city: New Orleans
country: United States
facility: Oschner Medical Center
state: Louisiana
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
city: Edegem
country: Belgium
facility: Antwerp University Hospital
state: Antwerp
city: Brussels
country: Belgium
facility: Uz Brussel
city: Brussels
country: Belgium
facility: Universitary Saint-Luc hospital
city: Gent
country: Belgium
facility: Ghent University hospital
city: Leuven
country: Belgium
facility: UZ Gasthuisberg
city: Lodelinsart
country: Belgium
facility: CHU de Charleroi site Marie Curie
city: Mons
country: Belgium
facility: Chu Ambroise Pare
city: Ottignies
country: Belgium
facility: Clinique Saint-Pierre
city: Winnipeg
country: Canada
facility: The Health Sciences Center University of Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Joensuu
country: Finland
facility: North-Karelia Central Hospital
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Lahti
country: Finland
facility: Päijänne Tavastia Central Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Nimes
country: France
facility: CHRU de Nîmes - Hôpital Universitaire Carémeau
city: Paris
country: France
facility: APHP Hôpital Bichat - Réanimation médicale et Maladies infectieuses
city: Pessac
country: France
facility: Chu de BORDEAUX Hôpital Haut-Leveque - Réanimation
city: Pringy
country: France
facility: CH Annecy Genevois - Réanimation
city: Athens
country: Greece
facility: ATTIKON University Hospital
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
state: Hong Kong SAR
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
city: Roma
country: Italy
facility: Ospedale San Filippo Neri
city: Roma
country: Italy
facility: San Giovanni Addolorata Hospital
city: Rome
country: Italy
facility: Sapienza, Universita di roma
city: Torino
country: Italy
facility: Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail
state: Johor
city: Kota Bharu
country: Malaysia
facility: Hospital Universiti Sains Malasysia
state: Kelantan
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
state: Pahang
city: Kuantan
country: Malaysia
facility: International Islamic University Malaysia Medical Center
state: Pahang
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Serdang
country: Malaysia
facility: Hospital Serdang
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
city: Coimbra
country: Portugal
facility: Centro Hospitalar Universitario de coimbra
city: Coimbra
country: Portugal
facility: Hospital Geral
city: Lisbon
country: Portugal
facility: Hospital de Santa Maria
city: Porto
country: Portugal
facility: Hospital S. João
city: Porto
country: Portugal
facility: Instituto Português de Oncologia do Porto Francisco Gentil
city: Vila Franca de Xira
country: Portugal
facility: Hospital Vila Franca de Xira
city: Barcelona
country: Spain
facility: Hospital Del Mar
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital de Bellvitge
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
Study officials:
affiliation: The University of Queensland
name: Jason A Roberts, PhD
role: PRINCIPAL_INVESTIGATOR
References: