Screening Anti-Fungal Exposure in Intensive Care Units

Antifungal Agents Clinical Trial

— SAFE-ICU  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03136926
• Other study ID #: SAFE-ICU Protocol V2
• Status: Recruiting
• Start date: January 2017
• Est. completion date: December 2018

Study information

• Verified date: June 2018
• Source: The University of Queensland
• Contact: Fekade B Sime, PhD
• Phone: +61 412 181 027
• Email: f.sime[@]uq.edu.au
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

Recruitment information / eligibility

• 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

Related Conditions & MeSH terms

• Antifungal Agents

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
The University of Queensland

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Finland,  France,  Greece,  Hong Kong,  Italy,  Malaysia,  Netherlands,  Portugal,  Spain, 

Outcome

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