Antifungal Agents Clinical Trial
— SAFE-ICUOfficial title:
An International, Multi-centre Prospective Pharmacokinetic Evaluation of Antifungal Drug Exposure in Intensive Care Unit Patients Receiving Conventional Dosing Regimens
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.
Status | Recruiting |
Enrollment | 150 |
Est. completion date | December 2018 |
Est. primary completion date | September 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
Australia | Royal Brisbane and Women's Hospital | Brisbane | Queensland |
Australia | The Royal Melbourne Hospital | Melbourne | Victoria |
Belgium | Universitary Saint-Luc hospital | Brussels | |
Belgium | Uz Brussel | Brussels | |
Belgium | Antwerp University Hospital | Edegem | Antwerp |
Belgium | Ghent University hospital | Gent | |
Belgium | UZ Gasthuisberg | Leuven | |
Belgium | CHU de Charleroi site Marie Curie | Lodelinsart | |
Belgium | Chu Ambroise Pare | Mons | |
Belgium | Clinique Saint-Pierre | Ottignies | |
Canada | Queen Elizabeth II Health Sciences Centre | Halifax | Nova Scotia |
Canada | The Health Sciences Center University of Manitoba | Winnipeg | Manitoba |
Finland | Helsinki University Central Hospital | Helsinki | |
Finland | North-Karelia Central Hospital | Joensuu | |
Finland | Kuopio University Hospital | Kuopio | |
Finland | Päijänne Tavastia Central Hospital | Lahti | |
Finland | Tampere University Hospital | Tampere | |
Finland | Turku University Hospital | Turku | |
France | CHRU de Nîmes - Hôpital Universitaire Carémeau | Nimes | |
France | APHP Hôpital Bichat - Réanimation médicale et Maladies infectieuses | Paris | |
France | Chu de BORDEAUX Hôpital Haut-Leveque - Réanimation | Pessac | |
France | CH Annecy Genevois - Réanimation | Pringy | |
Greece | ATTIKON University Hospital | Athens | |
Hong Kong | Prince of Wales Hospital | Hong Kong | Hong Kong SAR |
Italy | Azienda Ospedaliera Universitaria Pisana | Pisa | |
Italy | Ospedale San Filippo Neri | Roma | |
Italy | San Giovanni Addolorata Hospital | Roma | |
Italy | Sapienza, Universita di roma | Rome | |
Italy | Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino | Torino | |
Malaysia | Hospital Sultan Ismail | Johor Bahru | Johor |
Malaysia | Hospital Universiti Sains Malasysia | Kota Bharu | Kelantan |
Malaysia | University Malaya Medical Centre | Kuala Lumpur | |
Malaysia | Hospital Tengku Ampuan Afzan | Kuantan | Pahang |
Malaysia | International Islamic University Malaysia Medical Center | Kuantan | Pahang |
Malaysia | Hospital Serdang | Serdang | |
Netherlands | Radboud University Nijmegen Medical Centre | Nijmegen | |
Portugal | Centro Hospitalar Universitario de coimbra | Coimbra | |
Portugal | Hospital Geral | Coimbra | |
Portugal | Hospital de Santa Maria | Lisbon | |
Portugal | Hospital S. João | Porto | |
Portugal | Instituto Português de Oncologia do Porto Francisco Gentil | Porto | |
Portugal | Hospital Vila Franca de Xira | Vila Franca de Xira | |
Spain | Hospital de Bellvitge | Barcelona | |
Spain | Hospital Del Mar | Barcelona | |
Spain | Hospital Universitario Vall d'Hebron | Barcelona | |
Spain | Hospital Clínico Universitario de Valencia | Valencia | |
United States | Oschner Medical Center | New Orleans | Louisiana |
Lead Sponsor | Collaborator |
---|---|
The University of Queensland |
United States, Australia, Belgium, Canada, Finland, France, Greece, Hong Kong, Italy, Malaysia, Netherlands, Portugal, Spain,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Mortality | 30-day mortality | 30 days |
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