Antifungal AgentsSAFE-ICUNCT03136926
Screening Anti-Fungal Exposure in Intensive Care Units
An observational study of Antifungal Agents, run by The University of Queensland at 47 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Antifungal Agents
- How many people
- 150 participants
- Where
- 47 sitesin 13 countries
- Study dates
- Jan 2017to Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
47 sites in 13 countries.
47 sites in 13 countries
Belgium8 sites, 8 recruiting
- Recruiting
Universitary Saint-Luc hospital
Brussels, Brussels Capital, 1200
Xavier Wittebole, +32 2 764 28 69, xavier.wittebole@uclouvain.be
- Recruiting
Uz Brussel
Brussels, 1090
SPAPEN HERBERT, '32-3-4775117, Herbert.Spapen@uzbrussel.be
- Recruiting
Antwerp University Hospital
Edegem, Antwerp, 2650
Karolien Dams, '003238213635, Karolien.Dams@uza.be
Philippe Jorens, 003238215175
- Recruiting
Ghent University hospital
Ghent, 9000
Jan De Waele, +32 9 332 21 42, Jan.DeWaele@UGent.be
- Recruiting
UZ Gasthuisberg
Leuven, 3000
Joost Wauters, MD, PhD, (0032)16344275, joost.wauters@uz.kuleuven.ac.be
- Recruiting
CHU de Charleroi site Marie Curie
Lodelinsart, 6042
Joosten Anne, 003271923395, recherche.soinsintensifs@chu-charleroi.be
Cinderella Noel, 003271923397, recherche.soinsintensifs@chu-charleroi.be
- Recruiting
Chu Ambroise Pare
Mons, 7000
HAENTJENS LIONEL, 003265413708, lionel_haentjens@me.com
- Recruiting
Clinique Saint-Pierre
Ottignies, 1340
Nicolas De Schryver, +32 10 43 77 34, nicolas.deschryver@cspo.be
Finland6 sites, 6 recruiting
- Recruiting
Helsinki University Central Hospital
Helsinki
Miia Valkonen, miia.valkonen@hus.fi
- Recruiting
North-Karelia Central Hospital
Joensuu
Matti Reinikainen, Matti.Reinikainen@pkssk.fi
- Recruiting
Kuopio University Hospital
Kuopio
Ilkka Parviainen, Ilkka.Parviainen@kuh.fi
- Recruiting
Päijänne Tavastia Central Hospital
Lahti
Antti-Pekka Loisa, Antti-Pekka.Loisa@phsotey.fi
- Recruiting
Tampere University Hospital
Tampere
Harri Lemettinen, Harri.Lemettinen@pshp.fi
- Recruiting
Turku University Hospital
Turku
Mikko Järvisalo, Mikko.Jarvisalo@tyks.fi
Malaysia6 sites, 6 recruiting
- Not yet recruiting
Hospital Sultan Ismail
Johor Bahru, Johor, 80100
Nor'azim Mohd Yunos, +60177610588, nor.azim@monash.edu
- Not yet recruiting
Hospital Universiti Sains Malasysia
Kota Bharu, Kelantan, 16150
Mohd Zulfakar Bin Mazlan, +60129091447, ulfakar@usm.my
- Not yet recruiting
University Malaya Medical Centre
Kuala Lumpur, 50603
Mohd Shahnaz Hasan, +60192627277, shahnaz_hasan@um.edu.my
- Recruiting
Hospital Tengku Ampuan Afzan
Kuantan, Pahang, 25100
Janattul Ain Jamal, +60129572891, janattulain@gmail.com
- Not yet recruiting
International Islamic University Malaysia Medical Center
Kuantan, Pahang, 52200
Mohd Basri Mat Nor, +60199822105, basri.matnor@gmail.com
- Not yet recruiting
Hospital Serdang
Serdang
Noor Airini Ibrahim, +60126497403, nairini69@yahoo.com
Portugal6 sites, 6 recruiting
- Recruiting
Centro Hospitalar Universitario de coimbra
Coimbra, 3000-075
Joao Pedro Baptista, joaopedrobaptista@gmail.com
- Not yet recruiting
Hospital Geral
Coimbra
Ana Marques, anarvmarques@gmail.com
- Not yet recruiting
Hospital de Santa Maria
Lisbon
João M Ribeiro, jmiguel.ribeiro@sapo.pt
- Not yet recruiting
Hospital S. João
Porto
José M Pereira, jmcrpereira@yahoo.com
- Recruiting
Instituto Português de Oncologia do Porto Francisco Gentil
Porto
Filomena Faria, faria.filo@gmail.com
- Not yet recruiting
Hospital Vila Franca de Xira
Vila Franca de Xira
João G Pereira, joaogpster@gmail.com
Italy5 sites, 5 recruiting
- Not yet recruiting
Azienda Ospedaliera Universitaria Pisana
Pisa
Fabio Guarracino, f.guarracino@ao-pisa.toscana.it
- Not yet recruiting
Ospedale San Filippo Neri
Roma
Emma Comandini, emmacomandini62@gmail.com
- Not yet recruiting
San Giovanni Addolorata Hospital
Roma
Roberta Caccese, roberta.caccese@fastwebnet.it
- Not yet recruiting
Sapienza, Universita di roma
Rome, 161
Mario Venditti, 0039 06491749, mario.venditti@uniroma1.it
- Not yet recruiting
Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino
Torino, 10126
Giorgia Maiolo, 3491652600, giorgia.maiolo@gmail.com
Ilaria De Domenici, 3491652600, ilaria.dedomenici@gmail.com
France4 sites, 4 recruiting
- Not yet recruiting
CHRU de Nîmes - Hôpital Universitaire Carémeau
Nîmes, 30029
Claire ROGER, 04.66.68.30.50, claire.roger@chu-nimes.fr
Jean Yves LEFRANT, jean.yves.lefrant@chu-nimes.fr
- Not yet recruiting
APHP Hôpital Bichat - Réanimation médicale et Maladies infectieuses
Paris, 75018
Jean François TIMSIT, 01 40 25 77 02, jean-francois.timsit@bch.aphp.fr
- Not yet recruiting
Chu de BORDEAUX Hôpital Haut-Leveque - Réanimation
Pessac
Olivier JOANNES BOYAU, 05 57 65 68 66, Olivier.joannes-boyau@chu-bordeaux.fr
- Not yet recruiting
CH Annecy Genevois - Réanimation
Pringy, 74374
David BOUGON, 04 50 63 60 30, email dbougon@ch-annecygenevois.fr
Spain4 sites, 4 recruiting
- Recruiting
Hospital Del Mar
Barcelona, 8003
Sonia Luque, 0034-93-2483825, sluque@parcdesalutmar.cat
Santiago Garu, 0034-652128567, SGrau@parcdesalutmar.cat
- Not yet recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 8035
Jordi Rello, jrello@crips.es
- Not yet recruiting
Hospital de Bellvitge
Barcelona, 8907
Raphael Manez, rmanez@bellvitgehospital.cat
- Not yet recruiting
Hospital Clínico Universitario de Valencia
Valencia, 46010
Gerardo Aguilar, +34 961973500 ext. 973848, gerardo.aguilar@uv.es
Australia2 sites, 2 recruiting
- Recruiting
Royal Brisbane and Women's Hospital
Brisbane, Queensland, 4029
Jason Roberts, +61 7 3646 4108, j.roberts2@uq.edu.au
- Recruiting
The Royal Melbourne Hospital
Melbourne, Victoria, 3050
Monica Slavin, Monica.Slavin@mh.org.au
Jai Darvall, +61 3 9342 4120, jai.darvall@mh.org.au
Canada2 sites, 2 recruiting
- Not yet recruiting
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, 1276
Meghan MacKenzie, 902-999-8110, meghan.mackenzie@nshealth.ca
- Not yet recruiting
The Health Sciences Center University of Manitoba
Winnipeg, Manitoba
Anand Kumar, 204-291-0372, akumar61@yahoo.com
United States1 site, 1 recruiting
- Not yet recruiting
Oschner Medical Center
New Orleans, Louisiana, 70121
Leonardo Seoane, lseoane@ochsner.org
Greece1 site, 1 recruiting
- Recruiting
ATTIKON University Hospital
Athens, 14569
George Dimopoulos, +30.210.5832182, gdimop@med.uoa.gr
Hong Kong1 site, 1 recruiting
- Not yet recruiting
Prince of Wales Hospital
Hong Kong, Hong Kong SAR
Wai-Tat Wong, 852-92544847, wtwong@cuhk.edu.hk
Netherlands1 site, 1 recruiting
- Not yet recruiting
Radboud University Nijmegen Medical Centre
Nijmegen
Roger Bruggemann, Roger.Bruggemann@radboudumc.nl
About this study
Official 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:
Read more
- 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.
- Conditions
- Antifungal Agents
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Seven days
Secondary outcomes (1)
Mortality
30-day mortality
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2017
- Study startJan 2017
- Primary completionSep 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Antifungal AgentsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Queensland
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jason A Roberts, The University of Queensland
- Investigators
- Jason A Roberts, PhD, Principal investigator, The University of Queensland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03136926
- Sponsor's protocol ID
- SAFE-ICU Protocol V2
- Acronym
- SAFE-ICU
- Status last verified
- Jun 2018
- First submitted
- 21 Apr 2017
- Last updated
- 21 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Roberts JA, Sime FB, Lipman J, Hernandez-Mitre MP, Baptista JP, Bruggemann RJ, Darvall J, De Waele JJ, Dimopoulos G, Lefrant JY, Mat Nor MB, Rello J, Seoane L, Slavin MA, Valkonen M, Venditti M, Ceccarelli G, Wong WT, Zeitlinger M, Roger C. Are contemporary antifungal doses sufficient for critically ill patients? Outcomes from an international, multicenter pharmacokinetics study for Screening Antifungal Exposure in Intensive Care Units-the SAFE-ICU study. Intensive Care Med. 2025 Feb;51(2):302-317. doi: 10.1007/s00134-025-07793-5. Epub 2025 Feb 3.
PubMed 39899034
Study at a glance
From the registry record, last updated by the sponsor on 21 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An International, Multi-centre Prospective Pharmacokinetic Evaluation of Antifungal Drug Exposure in Intensive Care Unit Patients Receiving Conventional Dosing Regimens
- ClinicalTrials.gov ID
- NCT03136926
- Acronym / sponsor ID
- SAFE-ICU / SAFE-ICU Protocol V2
- Conditions
- Antifungal Agents
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- The University of QueenslandUniversity, hospital or other
- Study start
- Jan 2017 (actual)
- Primary completion
- Sep 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 2 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Probability of therapeutic target attainment
Time frame: 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).
1 secondary outcome
Mortality
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jun 2018.
- Derived from this study: PubMed 39899034Roberts JA, Sime FB, Lipman J, Hernandez-Mitre MP, Baptista JP, Bruggemann RJ, Darvall J, De Waele JJ, Dimopoulos G, Lefrant JY, Mat Nor MB, Rello J, Seoane L, Slavin MA, Valkonen M, Venditti M, Ceccarelli G, Wong WT, Zeitlinger M, Roger C. Are contemporary antifungal doses sufficient for critically ill patients? Outcomes from an international, multicenter pharmacokinetics study for Screening Antifungal Exposure in Intensive Care Units-the SAFE-ICU study. Intensive Care Med. 2025 Feb;51(2):302-317. doi: 10.1007/s00134-025-07793-5. Epub 2025 Feb 3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason A Roberts, PhD principal investigator
The University of Queensland
47 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Antifungal Agents, run by The University of Queensland at 47 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in Belgium, Finland, Malaysia, Portugal, Italy and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fekade B Sime, PhD (+61 412 181 027, f.sime@uq.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Probability of therapeutic target attainment (time frame: Seven days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03136926, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2018.