Screening Anti-Fungal Exposure in Intensive Care Units

NCT03136926 | Unknown

• 1 other identifier: SAFE-ICU Protocol V2
• Study Type: observational
• Target: 150
• Locations: 13 countries
• Sites: 47

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.

Conditions

Antifungal Agents

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Mortality

  30 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Queensland: lead

Study Sites (47)

Oschner Medical Center

New Orleans, Louisiana, 70121, United States

NOT YET RECRUITING

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

RECRUITING

The Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

RECRUITING

Antwerp University Hospital

Edegem, Antwerp, 2650, Belgium

RECRUITING

Universitary Saint-Luc hospital

Brussels, Brussels Capital, 1200, Belgium

RECRUITING

Uz Brussel

Brussels, 1090, Belgium

RECRUITING

Ghent University hospital

Ghent, 9000, Belgium

RECRUITING

UZ Gasthuisberg

Leuven, 3000, Belgium

RECRUITING

CHU de Charleroi site Marie Curie

Lodelinsart, 6042, Belgium

RECRUITING

Chu Ambroise Pare

Mons, 7000, Belgium

RECRUITING

Clinique Saint-Pierre

Ottignies, 1340, Belgium

RECRUITING

The Health Sciences Center University of Manitoba

Winnipeg, Manitoba, Canada

NOT YET RECRUITING

Queen Elizabeth II Health Sciences Centre

Halifax, Nova Scotia, 1276, Canada

NOT YET RECRUITING

Helsinki University Central Hospital

Helsinki, Finland

RECRUITING

North-Karelia Central Hospital

Joensuu, Finland

RECRUITING

Kuopio University Hospital

Kuopio, Finland

RECRUITING

Päijänne Tavastia Central Hospital

Lahti, Finland

RECRUITING

Tampere University Hospital

Tampere, Finland

RECRUITING

Turku University Hospital

Turku, Finland

RECRUITING

CHRU de Nîmes - Hôpital Universitaire Carémeau

Nîmes, 30029, France

NOT YET RECRUITING

APHP Hôpital Bichat - Réanimation médicale et Maladies infectieuses

Paris, 75018, France

NOT YET RECRUITING

Chu de BORDEAUX Hôpital Haut-Leveque - Réanimation

Pessac, France

NOT YET RECRUITING

CH Annecy Genevois - Réanimation

Pringy, 74374, France

NOT YET RECRUITING

ATTIKON University Hospital

Athens, 14569, Greece

RECRUITING

Prince of Wales Hospital

Hong Kong, Hong Kong SAR, Hong Kong

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Pisana

Pisa, Italy

NOT YET RECRUITING

Ospedale San Filippo Neri

Roma, Italy

NOT YET RECRUITING

San Giovanni Addolorata Hospital

Roma, Italy

NOT YET RECRUITING

Sapienza, Universita di roma

Rome, 161, Italy

NOT YET RECRUITING

Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino

Torino, 10126, Italy

NOT YET RECRUITING

Hospital Sultan Ismail

Johor Bahru, Johor, 80100, Malaysia

NOT YET RECRUITING

Hospital Universiti Sains Malasysia

Kota Bharu, Kelantan, 16150, Malaysia

NOT YET RECRUITING

Hospital Tengku Ampuan Afzan

Kuantan, Pahang, 25100, Malaysia

RECRUITING

International Islamic University Malaysia Medical Center

Kuantan, Pahang, 52200, Malaysia

NOT YET RECRUITING

University Malaya Medical Centre

Kuala Lumpur, 50603, Malaysia

NOT YET RECRUITING

Hospital Serdang

Serdang, Malaysia

NOT YET RECRUITING

Radboud University Nijmegen Medical Centre

Nijmegen, Netherlands

NOT YET RECRUITING

Centro Hospitalar Universitario de coimbra

Coimbra, 3000-075, Portugal

RECRUITING

Hospital Geral

Coimbra, Portugal

NOT YET RECRUITING

Hospital de Santa Maria

Lisbon, Portugal

NOT YET RECRUITING

Hospital S. João

Porto, Portugal

NOT YET RECRUITING

Instituto Português de Oncologia do Porto Francisco Gentil

Porto, Portugal

RECRUITING

Hospital Vila Franca de Xira

Vila Franca de Xira, Portugal

NOT YET RECRUITING

Hospital Del Mar

Barcelona, 8003, Spain

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 8035, Spain

NOT YET RECRUITING

Hospital de Bellvitge

Barcelona, 8907, Spain

NOT YET RECRUITING

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

NOT YET RECRUITING

Related Publications (1)

• 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.

  PMID: 39899034 DERIVED

Study Officials

• Jason A Roberts, PhD

  The University of Queensland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fekade B Sime, PhD

CONTACT

+61 412 181 027; f.sime@uq.edu.au

Jason A Roberts, PhD

CONTACT

+61 7 3365 5114; j.roberts2@uq.edu.au

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 21, 2017
• First Posted: May 2, 2017
• Study Start: January 1, 2017
• Primary Completion: September 1, 2018
• Study Completion: December 1, 2018
• Last Updated: June 21, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

PT (6); FI (6); AU (2); IT (5); ES (4); BE (8); CA (2); GR (1); NL (1); FR (4); HK (1); MY (6); US (1)